Facial pain is a frequent presenting complaint in the general clinic, the neurology clinic, and in the emergency department. Age, gender, and a detailed description of the pain complaint and accompanying symptoms will frequently suggest the correct diagnosis, whereas history, neurologic, and general physical examination generate a limited differential to help to further focus the investigation. Not infrequently, the patient has already been seen by several providers, often including a dentist, oral surgeon, or otolaryngologist, and testing and interventions have proved unhelpful. Many of these patients have normal or inconclusive imaging and normal examinations.
In this chapter, we will consider trigeminal neuralgia (TN), both idiopathic (classic) and secondary, the much rarer glossopharyngeal neuralgia (GN), migraine, and the trigeminal autonomic cephalgias (TACs), as well as herpetic and post herpetic neuralgia. Temporomandibular joint (TMJ) dysfunction and atypical facial pain (which has been recently renamed persistent idiopathic facial pain [PIFP]) will be briefly considered. Other causes of facial pain including cranial sinusitis, dental caries, acute glaucoma, and other causes of orbital and periorbital pain, temporal arteritis, and arterial dissections will be briefly discussed.
The practitioner should bear in mind that patients with facial pain, especially those with chronicity are frequently distraught, needy, and often quite complex.
I. TRIGEMINAL NEURALGIA
TN is probably the most common of facial pain disorders, and broadly speaking is among the more severe pain disorders known. Patients complain of very brief, electric-like or lancinating pain involving one or more branches of the trigeminal nerve. Typically the second and third divisions of the trigeminal nerve are involved, contiguously or individually. Rarely, the first division may also be involved, but almost never in isolation. The painful jolt lasts for seconds but can recur multiple times, often in bursts. The pain is almost always unilateral, and its overwhelming severity completely and visibly absorbs the patient when it strikes. Most commonly, there is no pain or paresthesias in between lancinating events and the painful episodes can dissipate as unexpectedly as they appear. The syndrome is often episodic, with painful epochs that stretch for weeks or months, and with spontaneous remissions lasting even years. Over time, typically measured in months or years, there appears to be a tendency toward increasing refractoriness to therapies. Very often, the patient will describe a trigger or aggravating feature that includes talking, chewing, brushing of teeth, application of makeup, shaving, casual contact with the effected area, or even a stimulus as subtle as an air current. Chewing and swallowing presents so much difficulty that the patient loses weight and may even suffer dehydration. The sudden, invasive, and miserable nature of TN is captured by the French phrase tic douloureux. In some patients, usually years after symptom onset, pain may become longer lasting with duller, more constant pain supervening together with paresthesias in the affected territory. Patients reporting these more complex pain phenomena may also have less predictable responses to invasive treatment, leading many authors to additionally classify these patients as “atypical TN.”
TN is etiologically divided into classic (or idiopathic) and symptomatic. Symptomatic TN may be due to compressive tumor (meningioma, acoustic neuroma, and epidermoid), infiltrative neoplasm, or to an inflammatory process, particularly multiple sclerosis. Other cited etiologies include vascular malformations, brainstem ischemia, facial trauma, and arteritis. Bilaterality strongly implies a secondary cause although most symptomatic TN cases are unilateral. Younger age favors a secondary cause but classic TN has been described in younger patients. The etiology of classic TN remains uncertain, but most authorities believe that demyelinative damage at the root entry zone due to vascular compression is causal. Neuroimaging studies, specifically MRI may show a secondary cause in up to 15% of cases and at least one neuroimaging study should be encouraged regardless of how typical a patient’s presentation may appear. High-field strength, high-resolution diffusion-tensor MR may be able to identify both the offending vessel and intrinsic change within the nerve, and so eventually become a reliable means of confirming classic TN.
TN has a prevalence of 3 to 6 per 100,000 becomes more frequent with age, particularly after age 60 and is nearly twice as frequent in women. Still, there is no completely secure clinical profile unequivocally establishing classical TN. On the other hand, neither involvement of the first division of the trigeminal nerve nor refractoriness to therapy should be considered completely reliable indicators of symptomatic TN. Most importantly, continuous pain or paresthesias or an abnormal neurologic examination prompts a thorough search for a symptomatic cause.
The general recommendation for initial therapy beyond analgesics is oral antiepileptic drug (AED), with carbamazepine most commonly considered first line therapy and where initial favorable response rates in classic TN approach 90%. Treatment with carbamazepine becomes less effective over time, partly due to increased hepatic elimination (autoinduction) but likely involving other, less understood mechanisms. Other agents including oxcarbamazepine, lamotrigine, gabapentin, or baclofen can be effective in monotherapy or as add on therapies. Familiarity with these agents, their side effects, and drug–drug interactions on the part of the treating physician are recommended.
There is general agreement that patients refractory to medical therapy should be considered for surgical intervention although evidenced-based data are sparse and broad agreement on how soon to seek surgical alternatives is lacking. A very effective approach with high rates of immediate pain relief and very effective long-lasting benefit involves craniotomy with microscopic vascular decompression (MVD) at the trigeminal root. High-resolution MRI has been employed to detect these offending vessels and predict successful MVD but reliability of these methods remains incomplete. Perioperative and postoperative complications occur, but are infrequent in the hands of experienced neurosurgeons. Less invasive partial destructive procedures include radiofrequency thermal rhizotomy, done very commonly and percutaneous balloon microcompression and less frequently, chemical rhizotomy. Stereotactic radiosurgery should be considered when patient infirmity or patient preference weighs against open surgery. The percutaneous procedures offer degrees of initial pain relief similar to that of MVD but also modestly less reliable sustained benefit. Complications potentially include deafferentation syndromes (anesthesia dolorosa or corneal hypoesthesia with keratitis) hearing loss or CSF leak. In the case of the least invasive nonmedicinal approach, stereotactic radio surgery, the patient must be made aware that pain relief will not become effective for a mean interval of about 1 month. Many experienced neurosurgeons are of the opinion and that too many patients have suffered for too long before being referred for definitive interventional therapy. The role of invasive therapy in patients with multiple sclerosis remains more controversial.
We stress that interventional procedures are effective in patients with classic TN but in patients with other causes of facial pain or frankly equivocal cases of TN, invasive procedures are wisely avoided or approached with appropriate circumspection.
II. GLOSSOPHARYNGEAL NEURALGIA
GN is similar to TN in that it presents with unilateral lancinating pain involving the posterior-lateral aspect of the throat (tonsil), the posterior aspect of the tongue, the ear, or larynx and as is the case for TN, remains a clinical diagnosis. Swallowing is a typical trigger as are speech or cough. The lancinating pain appears in some patients to trigger a coughing fit. A rare variant accompanied by syncope has been described which through presumed influence on vagus nerve outflow can cause recurrent brady-arrhythmia and even asystole. Like TN, GN may remit or relapse spontaneously but it is a far rarer disorder, with an estimated frequency of between 1/10th and 100th that of TN. It may be either idiopathic or symptomatic. Symptomatic causes include tumors of the skull base, infection, an expansile vertebral artery due to large atheroma, or malformation of the skull base. Otolaryngologic evaluation as well as neuroimaging evaluation is recommended. Elimination of triggered pain by the application of topical anesthetic may help support the diagnosis. Microvascular compression is considered the underlying cause of idiopathic GN by many authorities and so a surgical approach is often recommended if medical therapy is ineffective. High-resolution MRI lends some support to the theory of microvascular compression. In many cases, severity of GN may be milder relative to TN and in some instances, patient assurance has proved a sufficient remedy.
III. HERPES ZOSTER (HZ) NEURALGIAS
The acute or chronic neuralgia resulting from the segmental (dermatomal) recrudescence of herpes virus in the dorsal root ganglia is quite distinct clinically from TN and is generally readily recognized acutely by a characteristic, topographically distinct, unilateral rash. Because involvement of the trigeminal ganglion in reactivated latent herpes virus infection is common, HZ is a frequent cause of facial pain, especially in the elderly.
HZ has an overall incidence of between 1.5 and 3 per 1,000 annually, but this incidence rises to up to 6.5 per 1,000 by age 60 and up to 11 per 1,000 by age 70. Between 20% and 40% of all individuals will experience HZ in their lifetime. HZ affecting the first division of the trigeminal nerve (HZ ophthalmicus) is the second most common form of HZ, second only to the involvement of the thoracic dermatomes and comprises 10% to 20% of all HZ cases. The second and third divisions of the trigeminal nerve are rarely if ever affected in isolation. HZ begins with a prodrome that includes fatigue and malaise, headache and photophobia, rarely fever but very frequently includes a vague sensory prodrome in the involved dermatome that consists of tingling paresthesias, sometimes burning paresthesias, sometimes lancinating paresthesias, and sometimes allodynia. The HZ induced paresthesias are sensed as surface, dermatomal phenomena but a perceived deeper discomfort described as muscle or bone ache or even visceral pain referred to as myotomal phenomena in the older literature also occurs and can be severe. After a period of about 1 to 5 days, the typical rash (shingles), first maculopapular, and then frankly vesicular appears, restricted to a primary dermatome and parts of the immediately contiguous dermatomes. As the rash advances, the pain may worsen, and pruritus develops. The pain is mixed and unrelenting; a lancinating component may be prominent but never singular. A patient’s scratching will alter the appearance of the rash, with excoriations obscuring vesicles and it is therefore important to remain watchful for secondary bacterial infection. Bilateral or multifocal involvement is seen only in the immune compromised. Rarely, patients perceive a prodrome including sensory symptoms without evidence of rash. (This phenomenon together with the sequelae of HZ in the absence of observed rash have been termed “zoster sine herpete.”) The rash generally subsides over a period of 30 days; pain generally declines with it, but in 10% to 20% of patients, the pain persists beyond 30 days. This persistent pain syndrome termed postherpetic neuralgia (PHN) is the most common complication of HZ.
It is important to remember that HZ ophthalmicus often brings with it ocular involvement that can include exposure keratitis and uveitis but may rarely include retinal vasculitis, ischemic optic neuropathy, or necrotizing retinopathy. For these reasons, one should involve an ophthalmologist early in the course of illness, and treat the patient aggressively. The initiation of oral antiviral therapy within 72 hours of the appearance of rash reduces both the duration and severity of an outbreak while delayed treatment may still be beneficial. Intravenous antiviral therapy for the immune incompetent or for severe cases must be considered. Topical antiviral and either systemic or topical corticosteroid may be employed in selected cases.
Although generally self-limited, PHN may last many months or even years. PHN becomes more common in the elderly, and probably more debilitating and more difficult to treat in the older old. Manifestations include burning, lancinating or aching pain hyperalgesia, and allodynia. Allodynia is prominent and together with other neuropathic pain may severely disturb daily social function. The persistence of pain reflects CNS changes (“central pain”) and possibly persistent low-grade viral activity. Treatment is patient specific. Both gabapentin and pregabalin are Food and Drug Administration (FDA) approved for the treatment of PHN. A combination of opioid analgesics and AEDs can be used. Tricyclic antidepressants may also be effective. The application of topical sodium channel-directed analgesics such as lidocaine as an ointment or in patch form can be effective and topical capsaicin may be effective. The use of intrathecal corticosteroid is controversial.
The practitioner should be aware of rare but potentially devastating sequelae of HZ including cranial polyneuritis, CNS vasculitis, cerebral infarction, cerebral hemorrhage, postinfectious myelitis, progressive myelopathy, and necrotizing retinopathy. Childhood vaccination against HZ became available in 1995 and may alter the epidemiology of this disorder over time, but in the interim a much higher dose attenuated live virus vaccine approved by the FDA is available to people over age 60. As demonstrated by the initial trial and subsequently confirmed, the vaccine reduces the incidence of HZ by one-half. PHN is reduced by two-thirds.
IV. PRIMARY HEADACHE DISORDERS
Primary headaches, migraine, and its relatives can present with facial pain as a primary or principle feature. Chronic migraineurs, especially those without aura, will not infrequently attribute their problem incorrectly to recurrent sinus infection with infraorbital or retro-orbital pain. In the absence of signs and symptoms of infection and in the absence of unequivocal imaging support, a wary practitioner should consider the diagnosis of chronic migraine or chronic daily headache, even with tension type characteristics. A careful history of the patient’s pain complaint including quality, location, timing, duration, frequency, triggers, associated symptoms, and pattern of drug use or overuse should guide the clinician toward a correct diagnosis and best treatment. Headache of more than 1 hour’s duration, pain that is often but not always unilateral, the presence of photophobia, phonophobia, and a reluctance to move, anorexia if not frank nausea with vomiting, the presence of recurrent aura such as bright scotoma or transient hemianopsia or hemifacial or hemibody numbness or the presence of typical triggers such as bright lights, strong odors, noisy environments, or alcohol should influence the practitioner toward a consideration of migraine as a possible diagnosis. The localization of pain in migraine patients is variable, and although infrequent, it is not unusual for patients to report pain mostly involving the face or even entirely limited to the lower face.
Cluster headache (CH), the less common paroxysmal hemicranial headache and the very rare related headache variant, short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing or short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) syndrome can pose initial diagnostic uncertainty. These three pain syndromes are grouped collectively as the TACs. The pain of CH is always severe, usually peri- and retro-orbital, unilateral, and relatively short lasting. The pain is described as stabbing or knife-like, boring or drilling, burning or squeezing and in some patients may spread to the occiput and posterior cervical regions. Attack duration is typically from 15 minutes to 3 hours but most attacks last less than 1 hour. During the attack, the patient appears restless and agitated, a feature which effectively differentiates this form of headache from migraine. The attacks are cyclical, tend to occur at characteristic times of the day, and occur on a once up to several times daily basis for weeks or months and then spontaneously resolve. It is the cyclical grouping from which the term “cluster” originates. The most severe headaches are said to wake the patient from sleep early in the night, corresponding to the first rapid eye movement sleep cycle. The attacks are accompanied by a combination of lacrimation, conjunctival injection, nasal congestion, or rhinorrhea. Sometimes Horner syndrome can be observed. These autonomic manifestations are generally unilateral. Affected individuals are more commonly men and smokers. Recent data suggest lifetime prevalence could be as high as 1 in 1,000. Cluster pain is severe, suicidal ideation during attacks is not unusual, and aggressive treatment is mandatory. Multiple abortive therapies can be effective. Rapidly absorbed tryptans works; both sumatriptan and zolmitriptan are believed to be effective. High-flow inhaled nasal oxygen can also be an effective abortive therapy. Many different treatments are used by specialty clinics. Transitional and prophylactic therapies are often indicated. Treatment usually requires polypharmacy and ongoing therapy is probably best delivered by a practitioner familiar with the problem. Specialty clinic estimates suggest that 10% of chronic CH patients are resistant to or intolerant of all pharmacotherapy. Interventional therapy such as occipital nerve stimulation or hypothalamic deep brain stimulation may work but efficacy is uncertain and consideration of these therapies should be limited to very experienced centers. Although CH is distinctly clinically recognizable, MRI of the brain with special reference to the skull base is advisable on initial presentation.
Paroxysmal hemicrania consists of multiple severe short lasting bouts of pain, lasting only minutes, with a pain distribution which is unilateral, often orbital or supraorbital, retro-orbital or temporal. In SUNCT, the pain is even briefer, lasting seconds. The character of the pain in SUNCT and to a lesser degree in paroxysmal hemichrania make it difficult to distinguish these clinically from the pain of neuralgia but both syndromes are accompanied by cranial autonomic features that should distinguish them from TN. Paroxysmal hemicrania responds nearly always to indomethacin as does another headache syndrome with even briefer lasting painful jolts, primary stabbing headache. The extraordinarily rare SUNCT syndrome may respond to lamotrigine or one of the other newer AEDs. In rare patients, headache classifiable as SUNCT may represent a crossover form of TN and could respond to surgical therapy.
It must be remembered that primary headache including migraine and its variants remains a diagnosis of exclusion. Appropriate neuroimaging must be considered at initial presentation or if the clinical characteristics of the syndrome shift significantly.
V. PERSISTENT IDIOPATHIC FACIAL PAIN OR ATYPICAL FACIAL PAIN
Atypical facial pain arose historically as a diagnostic grouping in contradistinction to TN (or “typical” facial pain) and has recently been renamed PIPF by the International Headache Society who have generated a defining set of characteristics. These are chronicity, dull constant aching (or burning) pain with nonperiodic exacerbations, diffusely localized pain usually unilateral but not conforming to a nerve distribution, a normal neurologic examination, and pain without an attributable cause after adequate clinical and imaging investigation. PIFP patients are less commonly young and less commonly male, are frequently depressed and frequently have other accompanying somatic complaints. These patients too often come to neurologic attention after one or more interventions, often dental or sinus procedures that have failed to alleviate and may have even aggravated their complaint. A multidisciplinary approach to these patients is advocated and antidepressants are frequently helpful. Amitriptyline is an established therapy but selective norepinephrine and serotonin reuptake inhibitors such as duloxetine may be helpful. Unfortunately, therapy is rarely dramatically successful in patients with PIFP. For patients where the duration of the complaint is a many years long, it is important to obtain a history of the earliest presenting features. Some of these patients may have a chronically evolved form of TN. When the complaint is relatively new one, a rare patient may actually have an underlying pulmonary malignancy. These patients will be heavy smokers and generally have a prominent periauricular component to their pain syndrome.
VI. LOWER FACIAL AND ORAL PAIN
Both the general practitioner and the neurologist should be familiar with pain disorders involving the lower face. The most common of these are the temporomandibular disorders (TMJ syndromes). Although temporomandibular dysfunction presents principally with pain at the TMJ and its associated musculature, associated symptoms including ear pain, frontal facial pain, more generalized headache, cervical pain, and dizziness make TMJ disorders an important differential consideration in patients presenting with facial pain. Historically, the TMJ dysfunctions have been both overdiagnosed and overtreated. TMJ syndromes present principally with pain involving the TMJ and its associated musculature, aggravated by jaw function and associated with asymmetric movements of the jaw, painfully limited jaw opening and joint sounds. TMJ dysfunction presents most frequently in young adults, with a gender disparity favoring women in ratios of 3:1 or more. These disorders are generally self-limiting, and rarely present or persist beyond the age of 40. It is estimated that only 5% of symptomatic patients require any therapy at all, and it is believed that contrary to some historical practices, very few patients require invasive diagnostics or invasive therapies. The vast majority of patients with TMJ syndromes will respond to anti-inflammatory medications and conservative measures such as jaw appliances. The majority of patients refractory to these simple measures have a chronic pain syndrome and should be considered for multidisciplinary therapy, which may include benzodiazepines and norepinephrine reuptake inhibitors. Narcotic analgesics should be avoided. Physical findings in TMJ dysfunction include tenderness of the TMJ and associated musculature and painful, limited or asymmetric jaw opening. Evaluation by an appropriate dental or oral surgical practitioner is recommended.
Atypical odontalgia is a rare disorder that mimics common tooth pain. The syndrome is characterized by its chronic nature, by definition more than 4 months duration and is frequently seen following dental extraction (phantom tooth pain), other oral procedures, or oral trauma. On occasion, the syndrome appears to occur spontaneously. The pain is characterized by dull persistence but transient sharp pain is sometimes reported. This pain entity is said not to disturb sleep and may not be present at awakening or briefly thereafter. Hyperpathia and allodynia may be present while spread of the pain to contiguous structures is not uncommon. Once local pathology has been adequately excluded, typical treatments targeting neuropathic pain may prove helpful.
VII. OTHER CAUSES OF FACIAL PAIN
The signs and symptoms of acute infections of the oral cavity, the paranasal sinuses, or the eye are generally obvious. The practitioner must remain alert to the patient who has been treated surreptitiously and unsuccessfully for a poorly documented acute infection where an alternative diagnosis, inflammatory or neurologic, should be considered. Chronic sinusitis, especially when the deep sinuses are involved, can be clinically less apparent and could present with only vague head or facial pressure and malaise. Modern imaging, either coronal CT or when needed MRI, is highly sensitive to pathology in or neighboring the ethmoid or sphenoid sinuses. The possibility of chronic facial pain heralding the presence of invasive infection in diabetics or the immune compromised must not be overlooked.
Giant cell arteritis should be considered in patients above age 55 who present subacutely with temporal or facial pain coupled with marked fatigue and malaise. These patients may complain of scalp tenderness, jaw claudication on prolonged chewing, and most ominously, visual disturbance. Palpable tenderness of the superficial temporal artery or another branch of the extracranial carotid artery should be present on examination and an elevated erythrocyte sedimentation rate will be present in nearly 90% of cases. A timely temporal artery biopsy is essential to making the correct diagnosis.
Cranial neuropathies can present with pain prior to the development of neurologic deficits. Retrobulbar neuritis very frequently presents with pain on eye movement before monocular visual loss becomes apparent. Ischemic neuropathies involving the third or the sixth cranial nerves are typically painful although nonarteritic ischemic optic neuropathy is not.
Cervical arterial dissection can present with retro-orbital or more diffuse facial or occipital pain. Cervical pain need not be present and Horner syndrome can be either absent or overlooked. Pain frequently precedes cerebral ischemic manifestations so this entity is important to consider in young adults, especially if there is a recent history of minor head or neck trauma or cervical manipulation.
Acute glaucoma is associated with orbital and adjacent facial pain but the diagnosis is usually obvious because of corneal clouding and other eye changes. Subacute glaucoma can be more subtle on physical examination and can lead to a late or missed diagnosis. Facial pain or headache should not be readily attributed to refractive errors or eye strain.
Chronic facial pain accompanied by hyperpathia or allodynia can be a manifestation of a central pain syndrome. The most common of these involves the contralateral thalamus and is usually post ischemic. Generally, complete hemisensory loss will be present but on occasion, the loss can be restricted to the trigeminal distribution alone. This form of central pain may readily respond to tricyclic antidepressants such as amitriptyline or to antiepileptic medications such as lamotrigine or gabapentin.
Anesthesia dolorosa is a central pain syndrome that may follow any of the procedures performed to control TN. It is thought to be a consequence of excessive deafferentation and is characterized by the simultaneous presence of a constant, very unpleasant dysesthesia, and marked cutaneous facial sensory loss. The syndrome may not surface for weeks or months after an ablative procedure. Neurosurgeons have observed that lessening the degree of deafferentation can lessen the likelihood of anesthesia dolorosa following an ablative trigeminal procedure. This syndrome can be difficult to treat either medically or surgically. Experimental approaches utilizing either invasive or noninvasive brain stimulation technologies could prove effective in the near future.
VIII. CONCLUDING OBSERVATIONS
It should always be remembered that patients with a chronic complaint, even if that complaint has been thoroughly investigated, can develop new symptoms and become refractory to previously effective therapy. Changes in complaint or condition in an otherwise familiar patient could reflect a serious underlying pathology and may merit repeat neuroimaging. Patients with chronic facial pain may harbor an undisclosed malignancy or inflammatory process or a chronic infectious process. The presence of neurologic deficits on examination, be it a cranial nerve palsy, a sensory deficit in the trigeminal distribution, Horner syndrome or the presence of subjective complaints of dysesthesias, diplopia, hearing loss, or disequilibrium should alert the practitioner to these possibilities. Similarly, the presence of cervical lymphadenopathy, chronic nasal obstruction, proptosis, lid edema, serous otitis, or an objective bruit is potentially grave signs.
Patients with deficits should be appropriately imaged and referred. If patients with TN do not immediately respond to medication, they should be seen by a neurologist or neurosurgeon. If patients with TN fail medical therapy, consideration of early invasive treatment is generally appropriate. Because of its rarity, the diagnosis of GN should be confirmed by a neurologist or neurosurgeon. Patients with unusual headache syndromes should have their diagnosis confirmed by a neurologist and if management difficulties are encountered, managed by a neurologist with headache expertise. Patients with HZ ophthalmicus should be seen by an ophthalmologist even if the globe appears uninvolved. Patients with refractory PHN can be expected to do poorly following ablative therapy.
Patients with chronic facial pain would truly benefit from a medical home provided by either their primary care physician or an appropriate specialist, perhaps a neurologist, who can propose new avenues of investigation or therapy and help prevent inappropriate interventions.
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