Facial Pain and Neuromuscular Diseases

CLINICAL FEATURES: People of all ages are susceptible to Bell’s palsy, but middle-aged people are affected most frequently. Women are affected more often (71%) than men. Childhood involvement is usually associated with a viral infection, Lyme disease, or earache.

Considerable variation exists in the severity of signs and symptoms. The palsy is characterized by an abrupt loss of muscular control on one side of the face, imparting a rigid masklike appearance and resulting in the inability to smile, to close the eye, to wink, or to raise the eyebrow (Fig. 18-1). A few patients, especially those with MS, experience prodromal pain on the affected side before the onset of paralysis. Infrequently, bilateral involvement is seen. The paralysis may take several hours to become complete, but patients frequently awaken in the morning with a full-fledged case. Rapid onset of bilateral facial weakness should alert the clinician to the possibility of such diseases as Guillain-Barre syndrome, a form of sarcoidosis known as uveoparotid fever (see Heerfordt’s syndrome, page 339), or other types of vasculitis causing multiple cranial neuropathies. If multiple cranial nerve deficits accompany the observed facial weakness, then central nervous system (CNS) infectious diseases and basilar skull tumors must be considered in the differential diagnosis. When vertigo or tinnitus is a major symptom, an occult herpes zoster ear infection should be suspected, and the diagnosis may be changed to Ramsay Hunt syndrome (see page 252).

The corner of the mouth usually droops, causing saliva to drool onto the skin. Speech becomes slurred and taste may be abnormal. Because the eyelid cannot close, conjunctival dryness or ulceration may occur.

TREATMENT AND PROGNOSIS: No universally preferred treatment exists for Bell’s palsy. Histamine and other vasodilators may shorten the duration, as will systemic corticosteroids and hyperbaric oxygen therapy. Surgical decompression of the intratemporal facial nerve is used in select cases. Topical ocular antibiotics and artificial tears may be required to prevent corneal ulceration, and the eyelid may have to be taped shut.

Symptoms usually begin to regress slowly and spontaneously within 1 to 2 months of onset; more severe cases take longer, as do those in older patients. Overall, more than 82% of patients recover completely within 6 months. Residual symptoms that remain after 1 year will probably remain indefinitely. Recurrence is rare, except in Melkersson-Rosenthal syndrome.

CLINICAL FEATURES: Trigeminal neuralgia characteristically affects individuals older than 40 years of age (the average age at onset is 50 years), although it may affect persons as early as puberty. Women are affected slightly more often than men, and the right side is involved more often than the left. Any branch of the trigeminal nerve may be involved, but the ophthalmic division is affected in only 5% of cases. More than one branch may be involved, and the pain is occasionally bilateral.

Specific and strict criteria must be met for an accurate diagnosis (Box 18-3). If the pain pattern does not meet these criteria, then a different diagnosis should be considered. When these criteria are partially fulfilled, alternative terms such as atypical trigeminal neuralgia, atypical facial pain, and atypical facial neuralgia are applied.

In the early stages, the pain of trigeminal neuralgia may be rather mild and is often described by the patient as a twinge, dull ache, or burning sensation. This clinical presentation may be erroneously attributed to disorders of the teeth, jaws, and paranasal sinuses and lead to escalation of treatment and a variety of therapeutic misadventures. Many documented cases of idiopathic trigeminal neuralgia are preceded by this dull, continuous, aching type of jaw pain that may persist for days to years without obvious dental pathology before the onset of the characteristic paroxysmal pain in the same region of the face. This has come to be regarded in the literature as pretrigeminal neuralgia. Pretrigeminal neuralgia has been reported in approximately 18% of documented trigeminal neuralgia cases. Moreover, pretrigeminal neuralgia has shown a dramatic response to carbamazepine in controlled clinical drug trials.

There are long, asymptomatic refractory periods between painful attacks. With time, the attacks occur at more frequent intervals and the pain becomes increasingly intense. At this point, patients often state that the pain is like “a lightning bolt” or a “hot ice pick jabbed into the face.” A distinguishing feature of trigeminal neuralgia is that objective signs of sensory loss cannot be demonstrated on physical examination. The presence of objective facial sensory loss, facial weakness, or ataxia should raise the distinct possibility of a CNS tumor.

Although individual pains or pain spasms last only a few seconds, several attacks may follow each other for up to 30 minutes of rapidly repeating volleys. Patients often clutch at the face and experience spasmodic contractions of the facial muscles during attacks, a feature that long ago led to the use of the term tic douloureux (i.e., painful jerking) for this disease. Similar to other neuralgic disorders, a refractory period follows a paroxysm of pain during which time the pain cannot be elicited. This refractory period can be useful, clinically, in distinguishing neuralgic pain from a stimulus-provoked odontogenic pain source. The paroxysmal facial pain is occasionally accompanied by excess lacrimation, conjunctival injection, and intense headache. This presentation may represent the SUNCT (short-lasting, unilateral, neuralgiform headache with conjunctival injection and tearing) syndrome rather than trigeminal neuralgia. Other differential considerations include but are not limited to glossopharyngeal neuralgia, Raeder’s syndrome, atypical facial pain, and cluster headache. Raeder’s syndrome is applied to pain of trigeminal distribution usually in the ophthalmic distribution in association with an ocular sympathetic deficit comprising ptosis, miosis, and an impairment of sweating limited to the medial aspect of the forehead. Because this constellation of clinical findings may have a variety of causes, the recognition of Raeder’s syndrome serves only to draw attention to the region of the disturbance and does not imply causation.

When an obvious trigger point is present in trigem-inal neuralgia, a pain attack may be brought on by a stimulus to the area as mild as a breeze, a gentle movement, or a feather-light touch. Trigger points are found most frequently on the nasolabial fold, the vermilion border of the lip, or the midfacial and periorbital skin. Intraoral trigger points are uncommon but do occur, especially on the alveolus.

HISTOPATHOLOGIC FEATURES: No unique histopathologic characteristic to the nerves in trigeminal neuralgia exists, although the trigger points may show fibrosis and infiltration by small numbers of chronic inflammatory cells. Focal areas of myelin degeneration have been reported within the gasserian ganglion and along the course of the cranial nerve itself, but these also have been occasionally seen in persons without trigeminal neuralgia. MS patients with trigeminal neuralgia show unique amorphous plaques in the ganglion.

TREATMENT AND PROGNOSIS: There have been rare reports of spontaneous permanent remissions of trigeminal neuralgia. However, more often than not, this disease is characterized by a protean and protracted clinical course with regard to the frequency and severity of exacerbations. The initial treatment for trigeminal neuralgia is medical. Topical capsaicin cream (a nociceptive substance-P suppressor) over the affected skin may be effective. Almost all patients with trigeminal neuralgia respond favorably to the anticonvulsant, carbamazepine, and an unequivocal response to this medication can be used as a diagnostic test for this disease. Anticonvulsant medica-tions (phenytoin, carbamazepine, gabapentin) often are effective in pain control, probably because they decrease conductance in Na⁺ channels and inhibit ectopic (i.e., arising from abnormal sites) discharges. These drugs, unfortunately, often have severe side effects and may not be tolerated for long by the patient. Moreover, the pain usually returns on discontinuance of the medication. If drug treatment fails, then surgical therapy may be considered.

Various neurosurgical procedures such as microvascular decompression and radiofrequency rhizotomy also are effective in severe or refractory cases, especially in younger patients (Box 18-4). Recent reports have shown some success with gamma knife radiosurgery of the gasserian ganglion and its associated nerves.

Neurosurgical methods provide relief for years in the majority of trigeminal neuralgia patients. Repeated surgical procedures often are necessary, however, and techniques that deliberately damage neural tissues leave the patient with a sensory deficit. After surgery, up to 8% of patients develop distorted sensations of the facial skin (facial dysesthesia) or a combination of anesthesia and spontaneous pain (anesthesia dolorosa). Anesthesia dolorosa is a dreaded form of central pain that can occur after any neurosurgical procedure that causes a variable amount of sensory loss, but this complication occurs more commonly with proce-dures that totally denervate a region. Overall, long-term success from surgical procedures is 70% to 85%.

CLINICAL FEATURES: The age of onset for glossopharyngeal neuralgia varies from 15 to 85 years, but the average age is 50 years. There is no sex predilection, and only rarely is there bilateral involvement. The paroxysmal pain may be felt in the ear (tympanic plexus neuralgia), infra-auricular area, tonsil, base of the tongue, posterior man-dible, or lateral wall of the pharynx; however, the patient often has difficulty localizing the pain in the oropharynx.

The episodic pain in this unilateral neuralgia is sharp, lancinating (jabbing), and extremely intense. Attacks have an abrupt onset and a short duration (30- to 60-second bursts that may repeat for 5 to 30 minutes). The pain typically radiates upward from the oropharynx to the ipsilateral ear. Talking, chewing, swallowing, yawning, or touching a blunt instrument to the tonsil on the affected side may precipitate the pain, but a definite trigger zone is not easily identified. Because the pain is related to jaw movement, it may be difficult to differentiate it from the severe pain of temporomandibular joint dysfunction (TMD).

Patients frequently point to the neck immediately below the angle of the mandible as the site of greatest pain, but trigger points are not found on the external skin, except within the ear canal. Rarely, syncope, hypotension, seizures, arrhythmia, or cardiac arrest may accompany the paroxysmal pain, as may coughing or excessive salivation. As with trigeminal neuralgia, idiopathic and secondary forms of glossopharyngeal neuralgia exist. The clinician should be careful to rule out Eagle syndrome (see page 23) and other conditions before applying the glossopharyngeal neuralgia diagnosis. The literature suggests that approximately 25% of cases of glossopharyngeal neuralgia are the result of secondary causes such as neoplasms involving the skull base or aneurysms in the posterior cranial fossa.

TREATMENT AND PROGNOSIS: As in trigeminal neuralgia, glossopharyngeal neuralgia is subject to unpredictable remissions and recurrences. It is not unusual during the early stages for remissions to last 6 months or more. Painful episodes are of varying severity but generally become more severe and more frequent with time.

Approximately 80% of patients experience immediate pain relief when a topical anesthetic agent is applied to the tonsil and pharynx on the side of the pain. Because this relief lasts only 60 to 90 minutes, it is used more as a diagnostic tool and emergency measure than a long-term treatment. Repeated applications to a trigger point for 2 or 3 days may extend the pain-free episode enough to allow the patient to obtain much needed rest and nutrition. Carbamazepine, oxcarbazepine, baclofen, phenytoin, and lamotrigine may relieve the neuralgic pain for a long period, but no therapy is considered to be uniformly effective or even adequate. Moreover, glossopharyngeal neuralgia is considerably less responsive than trigeminal neuralgia to treatment with anticonvulsant medications. If the patient fails drug therapy, then surgical options should be considered. The preferred neurosurgical treatments are microvascular decompression or surgical sectioning of the glossopharyngeal nerve and the upper two rootlets of the vagus nerve.

CLINICAL FEATURES: The most significant complication of herpes zoster is the pain that is associated with acute neuritis and PHN. PHN is defined as pain persisting for anywhere from 1 to 6 months or more after the onset of the rash. Postherpetic pain is described as a burning sensation with episodic “stabbing” pains. Light touch over the previously involved area may elicit a painful response (tac-tile allodynia) from the patient. Changes in sensation within the affected area may result in hypoesthesia or hyperesthesia.

The pain of PHN should not be confused with “shocklike” pain of trigeminal neuralgia that can be triggered by similar stimuli. The pain is constant and described as “burning and aching.” The burning character of the pain is thought to be the result of spontaneous activity in nociceptor C fibers. The VZV damages the peripheral nerve by a combination of demyelination, wallerian degeneration, fibrosis, and sclerosis. The pain associated with PHN is thought to arise from a disturbed pattern of afferent impulses combined with the loss of some central inhibitory influence in the pain modulatory systems. The mechanism of the pain in PHN is characteristic of deafferentation pain. Pathologically, degenerative lesions are observed in the axons, the dorsal root ganglion, and the dorsal horn of the spinal cord.

Age appears to be the major risk factor associated with the development of PHN. Approximately 50% of patients over the age of 50 with herpes zoster report some pain in the affected dermatome after the resolution of the cutaneous presentation, and 75% of patients older than 70 years of age are afflicted. Severe pain in the acute phase of the disease (acute neuritis) combined with advanced age appears to make the patient more prone to the development of PHN. Another susceptible group consists of those patients with diseases that compromise immunity.

Clinically, scarring and pigmentary changes are observed within the affected dermatome. The pain is usually accompanied by a sensory deficit. Researchers have found lowered sensory thresholds for cold, warmth, vibration, and two-point discrimination in patients whose rash was followed by neuralgia pain. In one recent study, allodynia (i.e., pain in response to a nonnoxious stimulus) was present in 85% of patients with PHN.

TREATMENT AND PROGNOSIS: As with most diseases, the best treatment option is prevention. Many argue that the administration of antiviral medication (most notably famciclovir) or corticosteroids, either alone or in combination, early in the course of herpes zoster possibly could prevent the development of PHN. Patients with acute herpes zoster benefit from the administration of oral antivirals. Accelerated healing of the lesions and an attenuation of zoster-associated pain have both been reported in placebo-controlled clinical drug trials. Further research is necessary to determine the most predictable way of preventing PHN.

Once PHN has established itself, a variety of treatment options are available for pain management. In addition to the judicious use of analgesics, including both nonnarcotic and narcotic preparations, a wide variety of drugs ranging from gabapentin, pregabalin, and amitriptyline hydrochloride to topical agents, such as lidocaine patches, EMLA (eutectic mixture of lidocaine and prilocaine), and capsaicin (0.025%), have been reported to be beneficial in pain relief. The topical application of capsaicin, an extract of hot chili peppers, has been reported to deplete the neurotransmitter substance P from nerve terminals, thereby desensitizing them.

Tricyclic antidepressants such as amitriptyline, nortriptyline, and desiprimine have proven to be quite useful in the management of the persistent pain that characterizes PHN; however, the anticholinergic and cardiovascular side effects may limit their utility, especially in older patients. Amitriptyline has consis-tently proven to be the single most effective drug, with approximately 60% of patients reporting relief with this agent. Patients are started at a low dose (10 mg) and titrated to effect, with the majority of patients obtaining significant relief with a median dose of 75 mg daily. These medications are usually given at bedtime to prevent daytime somnolence and to improve tolerance. Patients who report a stabbing pain in addition to the burning sensation may derive additional benefit from the use of anticonvulsant medications such as carbamazepine or phenytoin. In recent studies, gabapentin and pregabalin have been shown to reduce pain associated with PHN by more than 30%, and these drugs are typically well tolerated in all patient cohorts.

Patients who fail medical therapy have a limited range of surgical treatments available to them. How-ever, the outcome of procedures (e.g., blockade of peripheral nerves, roots, or sympathetic nervous system; surgery at the level of the affected nerve [neurectomy] or dorsal root) is far from certain with regard to pain management.

CLINICAL FEATURES: Atypical facial pain affects women far more frequently than men. It usually develops during the fourth through sixth decades of life, but can occur as early as the teenage years. The pain may be localized to a small area of the face or alveolus (e.g., atypical odontalgia, “phantom” toothache) but more frequently affects most of a quadrant and may extend to the temple, neck, or occipital area. Patients have great difficulty describing the pain, but most often portray it as a continuous, deep, diffuse, gnawing ache; an intense burning sensation; a pressure; or a sharp pain. The patient may nominally describe the pain using such terms as “drawing, aching, or pulling.” It is important to differentiate the pain from that of trigeminal neuralgia (see page 861).

Bilateral involvement occasionally occurs, and patients frequently attribute the onset of the pain to trauma or a dental procedure. The mucosa of the affected quadrant appears normal but typically contains a zone of increased temperature, tenderness, or bone marrow activity (“hot spot” on technetium-99m methylene diphosphonate [MDP] bone scan). Radiographic changes are not present. In some cases initially diagnosed as atypical facial pain, significant underlying disease has ultimately been identified (e.g., nasopharyngeal carcinoma, occult lung tumors).

TREATMENT AND PROGNOSIS: Occasional cases of spontaneous remission are noted, but the great majority of atypical facial pain patients will obtain little relief without therapy. Symptoms tend to become more intense gradually, and patients become irritable, fatigued, and depressed. Most patients are not benefited substantially from the drugs used for trigeminal neuralgia, although the new anticonvulsant, gabapentin, dramatically reduces the pain in one third of affected patients. Opioid analgesics (codeine, fentanyl, hydrocodone, morphine, and oxycodone) may be of considerable benefit, but their effectiveness characteristically diminishes over time and, of course, they are associated with the risk of abuse and addiction.

The tricyclic antidepressants (amitriptyline, nortriptyline) are popular therapies for neuropathic pain. They appear to block reuptake of norepinephrine and serotonin, transmitters released by pain-modulating systems in the spinal cord and brain stem, thereby allowing long periods of diminished neural activity. Other antidepressants (e.g., the selective serotonin reuptake inhibitors, paroxetine and citalopram) are generally not as effective as the tricyclic antidepressants for managing atypical facial pain, although some patients may respond to this therapy. It is important to remember, however, that antidepressant medications may be quite hazardous to frail older adults or to patients with coronary disease. When a localized area (usually alveolar) of tenderness can be found in the quadrant of pain, the application of topical capsaicin or injection with local anesthetics may be temporarily beneficial. Psychotherapy, behavior modification, transcutaneous electric nerve stimulation, and sympathetic nerve blocks are helpful in a subset of patients with atypical facial pain.

The frequent failure of medical treatment for atypical facial pain may lead to surgical intervention, usually the removal of a portion of the affected trigeminal nerve branch or the injection of a caustic solution (phenol, glycerol, alcohol) into the nerve, designed to destroy a portion of the nerve. These therapies often provide relief for several weeks or months, but there is seldom a permanent cure.

CLINICAL AND RADIOGRAPHIC FEATURES: NICO characteristically affects women 35 to 60 years of age but has been diagnosed in men and in teenagers. Third molar regions are affected in half of all cases, but any alveolar site may become involved, as may the walls of the sinuses and the mandibular condyle. At least one third of patients have more than one maxillofacial site of involvement, and 10% have lesions in all four alveolar quadrants.

Patients often have trouble describing and localizing their pain, which can be intermittent or constant, deep or superficial, aching or sharp, mild or extremely intense. Most often the pain is described as a deep ache or sharp bone pain. It typically begins as quite mild and vague, increasing slowly in frequency and intensity over months and years, but may also have a sudden onset, especially after a dental procedure using vasoconstrictors in the anesthetic. The pain may roam in the general anatomic area or be referred some distance from the affected bone (neck, shoulder). Many describe pressure and deep burning sensations, and local anesthesia typically relieves the pain.

Osteonecrosis is not visualized readily on radiographs, but when visible it usually appears as an area of regional osteoporosis or ill-defined radiolucency, often with irregular vertical remnants of lamina dura representing old extraction sites (Fig. 18-2). Occasional lesions show an admixture of irregular sclerotic and radiolucent areas (ischemic osteosclerosis), or there may be a faint central sclerotic oval surrounded by a thick radiolucent circle that is, in turn, surrounded by a thick but faint sclerotic ring (bull’s-eye lesion). More than 60% of the lesions will exhibit a hot spot of increased isotope uptake with the technetium-99m MDP bone scan (Fig. 18-3).

HISTOPATHOLOGIC FEATURES: The microscopic appearance of ischemic osteonecro-sis depends on the duration and intensity of the diminished marrow blood flow. The features of bone marrow edema include dilated marrow capillaries and sinusoids, serous ooze (plasmostasis) around blood vessels and adipocytes, wispy fibrous streaming (ischemic myelofibrosis) between fat cells, areas of dense fibrosis (intramedullary fibrous scar), and a light sprinkling of chronic inflammatory cells in regions of myelofibrosis (Fig. 18-4). Bony trabeculae usually remain viable at this stage but are inactive, thin, and often widely spaced.

Degenerative extracellular cystic spaces (cavitations) are commonly seen and may dominate the picture, eventually coalescing to form spaces large enough to extend from cortex to cortex (Fig. 18-5). Focal areas of marrow hemorrhage (microinfarction) are frequently present and considered by some to be pathognomonic for osteonecrosis.

Bubbles of coalesced, liquefied fat (oil cysts) may be seen. However, because high-speed rotary instruments can produce similar bubbles as an artifact, it is important that only hand-curetted marrow samples be submitted for histopathologic evaluation.

Bone death, when present, is represented by focal loss of osteocytes. However, this feature can be evaluated properly only if formic acid or another very weak acid is used for slow, gentle laboratory decalcification. In addition, smudged, globular, often dark masses of calcific necrotic detritus may be seen. These represent destroyed trabeculae that have literally dissolved over time and contributed their calcium to other salts precipitated within necrotic fat. The heat of high-speed rotary instrumentation can create similar calcific debris, but this debris remains at the edges of tissue fragments.

TREATMENT AND PROGNOSIS: Antibiotics may temporarily diminish the associated pain of NICO in those cases with a superimposed low-grade infection (chronic nonsuppurative osteomyelitis), but the pain typically returns when antibiotics are stopped. Usually the diseased marrow must be removed surgically by decortication and curettage. Once removed, the defect frequently heals and the intense facial pain subsides dramatically or disappears completely, although pain abatement may take several months to occur. Unfortunately, one third of patients thus treated experience no pain relief. In addition, the disease has a strong tendency to recur or to develop in additional jawbone sites. A repetition of the surgical procedure is, therefore, often necessary. Overall, the cure rate (free of pain for at least 5 years) for curettage is better than 70%.

CLINICAL FEATURES: Cluster headache may occur at any age, although it usually affects persons in the third and fourth decades of life and is rare before puberty. There is a strong male predilection (a 6:1 male-to-female ratio). The pain is almost always unilateral and follows the distribution of the ophthalmic division of the trigeminal nerve.

It is usually felt deep within or behind the orbit, radiating to the temporal and upper cheek regions. However, it may simulate a toothache or neuralgic jaw pain in the anterior maxillary region. Because of this, patients may be treated inappropriately for dental pain with endodontic therapy or tooth extraction, which is thought to be successful when the pain subsequently resolves. When each successive cluster returns, the next tooth is treated, sometimes resulting in multiple, repeated episodes of unnecessary dental therapy.

The pain is described as paroxysmal (i.e., abrupt onset) and intense, with a burning or lancinating quality and without a trigger zone. The attacks may last from 15 minutes to 3 hours and occur up to eight times daily (or on alternate days). The cluster periods typically last for weeks, with the intervening periods of remission usually lasting for months (sometimes years). The pain often begins at the same time in a given 24-hour period (alarm clock headache), with most attacks occurring in the middle of the night.

A chronic form occurs occasionally, with no re-missions for years at a time, and episodic forms may convert to the constant, chronic form. In addition, cluster headache is rarely accompanied by the aura so common to migraine headache. An important behavioral difference between migraine and cluster headache is that the patient is usually hyperactive during the latter and retreats to a dark, quiet room during the former.

In addition to the pain, the patient may experience autonomic alterations such as nasal stuffiness, tearing, facial flush, or congestion of conjunctival blood ves-sels. The latter sign, especially when associated with increased intraocular pressure, may indicate chronic paroxysmal hemicrania (Sjaastad syndrome), a rare syndrome with short-duration, highly recurring, nonclustered pain (see following topic).

TREATMENT AND PROGNOSIS: The proper diagnosis is important to avoid sequential, unnecessary endodontic or extraction procedures. Systemic prednisone, ergotamine, lithium carbonate, indomethacin, methysergide maleate, and verapamil all provide relief in some cases. Sumatriptan (agonistic to 5-HTID receptors) and other drugs of this class shorten the symptoms in 74% of cases. However, no single drug is universally effective. Inhaling oxygen may abort impending attacks, and various neurosurgical interventions to the affected nerve have provided relief in some patients, as has the recently reported use of gamma knife radiosurgery. Overall, only 50% of patients with cluster headache benefit significantly and permanently from the available therapeutic modalities.

It is important to distinguish cluster headache from chronic paroxysmal hemicrania because the latter disease responds almost universally to indomethacin.

CLINICAL FEATURES: In contradistinction to cluster headache, paroxysmal hemicrania is more common in women by a ratio of 2:1. The headache is for the most part strictly unilateral, and the pain is centered on the ocular, maxillary, temporal, and frontal regions. The symptoms typically last from 2 to 30 minutes, and the pain is described as a “boring” sensation that can be excruciating in terms of severity. The headache has an abrupt onset and an equally abrupt cessation. Ipsilateral cranial autonomic features such as lacrimation, conjunctival injection, and rhinorrhea also invariably occur. The patient may experience anywhere from 2 to 40 attacks daily, and the mean attack frequency is 14 per day. The headaches occur regularly throughout the 24-hour day and do not demonstrate a preponderance of nocturnal attacks as is commonly observed in cluster headache. About half of these patients desire reductions in stimuli similar to the preference demonstrated by those with migraines; the remaining 50% prefer hyperactivity during the attack similar to the response preference of individuals with cluster headache.

TREATMENT AND PROGNOSIS: Indomethacin is the treatment of choice for paroxysmal hemicrania. Effective resolution of the headache is prompt, typically occurring within 1 to 2 days of initiating the effective dose. The therapeutic trial of oral indomethacin should be initiated at 25 mg three times daily for 10 days. If the response is suboptimal, then the dosage should be increased to 50 mg three times daily for an additional 10 days. If there is a suspicion that the optimal dose has not been achieved, the dosage can be increased further to 75 mg three times daily for an additional 14 days. The typical maintenance dose is between 25 mg and 100 mg daily, but higher doses can be tolerated relatively well. A “drug holiday” should be attempted at least once every 6 months because long-lasting remissions have been reported in some patients after cessation of indomethacin. Long-term treatment with indomethacin may result in the gastrointestinal side effects common to this class of drugs. These side effects can be effectively managed with antacids, histamine H₂-receptor antagonists, or proton pump inhibitors. In patients who fail to demonstrate a predictable response to indomethacin, the diagnosis of paroxysmal hemicrania should be reconsidered.

CLINICAL FEATURES: Migraine affects women three times more frequently than men, and women tend to experience more severe attacks than men. The disease is most prevalent in the third through fifth decades of life, but the first symptoms often begin at puberty or shortly thereafter.

The unilateral headache lasts for 4 to 72 hours and is usually felt in the temporal, frontal, and orbital regions, as well as occasionally in the parietal, postauricular, or occipital areas. It begins as a poorly localized discomfort in the head that soon becomes a mild ache and then increases in severity over the next 30 minutes to 2 hours. At its peak, the pain has a throbbing quality, is quite severe, and is typically associated with nausea, vomiting, diarrhea, photophobia, and phonophobia. Usually, the pain is so severe as to be incapacitating, and the patient must lie down in a dark, quiet room. The headache recurs frequently, although the time between attacks varies widely. Rarely, bilateral examples occur.

It is important for the dentist to remember that referred migraine pain may initially mimic a toothache, especially of the anterior maxilla. Symptoms may also mimic sinusitis or allergic rhinitis.

Many migraineurs experience an “aura” before the actual headache pain. The aura may appear as visual hallucination, “seeing sparks” (scintillation), temporary and partial blindness, partial or complete loss of light perception (scotoma), nausea, vertigo, lethargy, mental confusion, loss of the ability to express thou-ghts (aphasia), or unilateral facial paresthesia or weakness.

TREATMENT AND PROGNOSIS: Nonpharmacologic approaches to the management of migraine involve the recognition and avoidance of known environmental triggers, as well as volitional modulation of the stress response (cognitive behavioral therapy). The pharmacologic treatment of migraine includes a wide variety of medications, and the two basic forms, with and without aura, respond in a similar fashion. The drugs that have shown the greatest efficacy in the treatment of migraine are members of the following three pharmacologic classes: (1) antiinflammatory agents, (2) 5-HT₁ agonists, and (3) dopamine antagonists. The optimal treatment regimen for a migraine attack depends primarily on the severity of the attack and must be individualized for each patient. Severe attacks frequently are diminished by ergotamine tartrate, perhaps combined with caffeine, aspirin, acetaminophen, phenobarbital, or belladonna. The drugs known as triptans are selective 5-HT₁ receptor agonists, and a variety of these medications are now available for the treatment of acute migraine attacks. Less severe but more frequent attacks are best treated prophylactically using other ergot compounds (e.g., methergine), b-adrenergic agents (e.g., propranolol, metoprolol), calcium channel blockers (e.g., nifedipine, diltiazem), or serotonin receptor agonists (e.g., methysergide, cyproheptadine). Some patients are aided by simple pressure on the ipsilateral carotid artery. The headaches tend to become less severe and less frequent over time, with or without effective therapy.

CLINICAL FEATURES: Women are affected by temporal arteritis somewhat more often than men, and patients are usually older than 50 years of age at the time of diagnosis (average age, 70 years). The disease is most frequently a unilateral, throbbing headache that is gradually replaced by an intense, aching, burning temporal and facial pain. The throbbing frequently coincides with the patient’s heartbeat (systole), and the pain may be lancinating. The superficial temporal artery is exquisitely sensitive to palpation and eventually appears erythematous, swollen, tortuous, or rarely ulcerated.

Most patients complain of pain during mastication (jaw claudication) or with the wearing of hats (pressure over the artery). The pain occasionally mimics toothache or a neuralgic jaw or tongue pain. Significantly, ocular symptoms, such as loss of vision or retro-orbital pain, may be the first complaint. Prompt recognition of signs and symptoms of temporal arteritis is important because it is a preventable cause of blindness. The blindness is caused by involvement of the posterior ciliary artery supplying the optic disc, which results in ischemic papillopathy. The visual loss may be transient or permanent, unilateral or bilateral.

Fever, malaise, fatigue, nausea, anorexia, vomiting, sore throat, and earache often occur, perhaps as prodromal symptoms, and the erythrocyte sedimentation rate is usually elevated. A generalized muscle aching and stiffness (polymyalgia rheumatica) frequently follow an acute attack. Because muscle and joint aches are quite common in older adults, the potential exists for missed opportunities in the diagnosis and management of temporal arteritis.

HISTOPATHOLOGIC FEATURES: Biopsy confirms the diagnosis of temporal arteritis. Microscopic changes tend to be segmental and can be missed if the specimen is too small. At least 1 cm of the affected vessel must, therefore, be examined for proper evaluation.

The disease is characterized by chronic inflammation of the tunica intima and tunica media of the involved artery, with narrowing of the lumen from edema and proliferation of the tunica intima. Necrosis of the smooth muscle and elastic lamina is frequent. A variable number of foreign body-type multinucleated giant cells are mixed with macrophages, plasma cells, and lymphocytes. Thrombosis or complete occlusion of the lumen is not unusual.

TREATMENT AND PROGNOSIS: Temporal arteritis responds well to systemic and local corticosteroids; the symptoms subside within a few days. However, many cases are chronic and need treatment for years. In addition, permanent loss of vision occurs in more than 50% of untreated patients (and even in the occasional patient refractory to treatment). With some individuals, vascular involvement is so widespread throughout the body that the disease is fatal, even with aggressive corticosteroid therapy.

CLINICAL FEATURES: Myasthenia gravis is more common in females (1:2 male-to-female ratio). It can begin at any age, and congenital cases have been reported. The disease appears as a subtle but progressive muscle weakness that is most frequently noticed first in the small muscles of the head and neck (Box 18-7).

Repeated muscle contractions, in particular, lead to progressively less power in the contracting muscle; hence, affected patients usually become weaker as the day progresses. The muscles of mastication may become so weak from eating a single meal that the jaws literally “hang open.” Bite force is especially weak when circulating AChR antibody titers are high. Lateral tongue forces exerted during swallowing, speech, and mastication, are reduced significantly in a number of patients.

DIAGNOSIS: The diagnosis of myasthenia gravis is based on the clinical symptoms, an elevated serum AChR antibody level, and improved strength after intravenous (IV) injection of edrophonium, a cholinesterase inhibitor. Degenerated muscle fibers are the only characteristic histopathologic feature, with fibers appearing much smaller than normal (hypotrophy, atrophy), having fewer nuclei, and showing a loss of the normal rounded cross-sectional appearance.

TREATMENT AND PROGNOSIS: The prognosis for myasthenia gravis is usually good. Spontaneous remission sometimes occurs, and approximately 10% of patients never have more than weak eye muscles. Unfortunately, more severe cases often pro-gress, after months or years, to permanent muscular weakness and wasting of the neck, limbs, and trunk. Respiratory paralysis is sometimes a fatal complication.

The defective neuromuscular transmission can be reversed partially by cholinesterase inhibitors (e.g., edrophonium, neostigmine), often in combination with intermittent corticosteroid therapy. For patients with evidence of thymoma or with elevated AChR antibody titers, thymectomy is recommended. Complete, permanent recovery often results from thymectomy and, to a lesser extent, from medical therapy.

CLINICAL FEATURES: Progressive muscular atrophy occurs in childhood. Most cases occur at birth or within the first few months of life, although adult onset is rarely seen. Males and females are affected equally. There is progressive limb weakness and sensory disturbances, which result in difficulty in walking, leg pain, paresthesia, and atrophy of the feet and hands. Facial muscles are spared.

Progressive bulbar palsy typically affects children and young adults and has no gender predilection. It usually begins with a subtle but progressive difficulty in speaking or swallowing (dysphagia). Attempts to swallow food produce bouts of choking and regurgitation, with liquids frequently thrown into the nasopharynx and nasal sinuses because of palatal paralysis. Chronic hoarseness may develop. Atrophy of the facial muscles, tongue, and soft palate eventually occurs, as do weakness and spasticity of the limbs. There are no altered sensory perceptions.

ALS (commonly called Lou Gehrig disease, named after the professional baseball player who died of the disease) affects males more frequently than females and begins to manifest itself in middle age (the average age of onset is 59 years). The disease begins with difficulty in walking because of bilateral, generalized leg stiffness. Occasionally, one leg is affected more than the other, forcing the patient to drag it behind the other. Swallowing difficulty develops early in 29% of cases.

The physical examination in ALS reveals spastic quadriparesis, often with a remarkable increase in the tendon reflexes of all four limbs and with extensor plantar responses. Small, synchronous, subcutaneous muscle contractions (fasciculation) of the shoulders and thighs are an early symptom, with muscle atrophy eventually developing at affected sites. Central reflexes, such as those of the abdomen, are not altered until late in the disease, and there are no changes in sense perception. Dysfunction of the muscles controlled by the medulla oblongata (bulbar paralysis) appears late in the disease, predominantly as spasticity and weakness. Patients become completely disabled, often requiring respiratory support and gastrostomy.

TREATMENT AND PROGNOSIS: Although each of these conditions may have temporary remissions, the course of motor neuron disease is invariably fatal. Progressive muscular atrophy and progressive bulbar palsy almost always result in death within 2 years, usually from respiratory distress caused by weak intercostal muscles.

ALS usually results in death within 5 years of diagnosis, most often from respiratory failure or cachexia, although 20% of patients survive more than 10 years without ventilator use. The antiglutamate agent, riluzole, has shown some promise in slowing the progression of ALS and improving the morbidity in patients with disease of bulbar onset, but in general there is no cure at this time. Palliative and rehabilitative strategies are used to ease suffering.

CLINICAL FEATURES: Women are four to seven times more likely to have burning tongue syndrome than men. The syndrome is rare before the age of 30 years (40 years for men), and the onset in women usually occurs within 3 to 12 years after menopause.

This disorder also has a typically abrupt onset, although it may be quite gradual. The dorsum of the tongue develops a burning sensation, usually strongest in the anterior third. Occasionally, patients will describe an irritated or raw feeling. Mucosal changes are seldom visible, although some patients will show diminished numbers and size of filiform papillae, and individuals who rub the tongue against the teeth often have erythematous and edematous papillae on the tip of the tongue. If the dorsum is significantly erythematous and smooth, an underlying systemic or local infectious process, such as anemia or erythematous candidiasis, should be suspected.

Close questioning often determines that additional oral sites are affected similarly, especially the anterior hard palate and the lips. There is seldom a significant decrease in stimulated salivary output in tests, despite the frequent patient complaint of xerostomia. Salivary levels of various proteins, immunoglobulins, and phosphates may be elevated, and there may be a decreased salivary pH or buffering capacity.

One frequently described pattern is that of mild discomfort on awakening, with increasing intensity throughout the day. Other affected patients describe a waxing and waning pattern that occurs over several days or weeks. Usually the condition does not interfere with sleep. A persistently altered (salty, bitter) or diminished taste may accompany the burning sensation. Contact with hot food or liquid often intensifies the symptoms. A minority describe a constant degree of discomfort.

As with other chronic discomforts, affected pa-tients frequently demonstrate psychologic dysfunction, usually depression, anxiety, or irritability. The dysfunction often disappears, however, with resolution of the burning or painful tongue condition, and there is no correlation between duration and intensity of the burning sensation and the amount of psychologic dysfunction.

TREATMENT AND PROGNOSIS: If an underlying systemic or local cause can be identified and corrected, the lingual symptoms should disappear. Almost two thirds of patients with idiopathic disease show at least some improvement of their symptoms when they take one of the mood-altering drugs (e.g., chlordiazepoxide). Additional therapies that have been used include clonazepam, a-lipoic acid (thioctic acid, a neuroprotective drug), amitriptyline, transcutaneous electrical nerve stimulation, analgesics, antibiotics, antifungals, vitamin B complex, and psychologic counseling. However, none of these treatments has been proven to be effective in a double-blind, placebo-controlled trial.

The long-term prognosis for idiopathic burning tongue or mouth syndrome is variable. It is reported that one third to one half of patients experience a spontaneous or gradual remission months or years after the onset of symptoms. However, other patients may continue to experience symptoms throughout the rest of their lives. Even though the condition is chronic and may not always respond to therapy, patients should be reassured that it is benign and not a symptom of oral cancer.

CLINICAL FEATURES: In contrast to hypogeusia, dysgeusia is discerned promptly and distressingly by affected individuals. The clinician must be certain that the patient’s alteration is, in fact, a taste disorder rather than an olfactory one, because 75% of “flavor” information (e.g., taste, aroma, texture, temperature, irritating properties) is derived from smell. Abnormal taste function should be verified through formal taste testing by using standard tastants that are representative of each of the four primary taste qualities (i.e., sweet, sour, salty, bitter) in a nonodorous solution. Additional electrical and chemical analysis of taste bud function is frequently required. Because this is outside the scope of most general practices, patients are typically referred to a taste and smell center.

Affected patients may describe their altered taste as one of the primary ones, but many describe the new taste as metallic, foul, or rancid. The latter two are more likely to be associated with aberrant odor perception (parosmia) than with dysgeusia. The altered taste may require a stimulus, such as certain foods or liquids, in which case the taste is said to be distorted. If no stimulus is required, then the dysgeusia is classified as a phantom taste.

TREATMENT AND PROGNOSIS: If an underlying disease or process is identified and treated successfully, the taste function should return to normal. For idiopathic cases there is no effective pharmacologic or surgical therapy. Dysgeusia in particular tends to affect lifestyles and interpersonal relationships significantly, perhaps leading to depression, anxiety, or nutritional deficiencies from altered eating habits. Fortunately, two thirds of dysgeusia patients experience spontaneous resolution (average duration, 10 months). Idiopathic hypogeusia is less of a problem for the patient, but tends to slowly become worse over time. Occasionally, even this will undergo spontaneous resolution.

CLINICAL FEATURES: The presenting signs and symptoms of Frey syndrome include sweating, flushing, warmth, and occasionally pain in the preauricular and temporal regions during chewing. Within 2 months to 2 years (average, 9 months) after the nerve injury, the sweating and flushing reactions commence and become steadily more severe for several months, remaining constant thereafter. When flushing occurs, the local skin temperature may be raised as much as 2° C. This may occur without sweating, especially in females. Pain, when present, is usually mild, and hypesthesia (hypoesthesia) or hyperesthesia are common features.

To detect sweating, Minor’s starch-iodine test may be used. A 1% iodine solution is painted on the affected area of the skin. This solution is allowed to dry, and the area is then coated with a layer of starch. When the patient is given something to eat, the moisture of the sweat that is produced will mix with the iodine on the skin. This allows the iodine to react with the starch and produce a blue color (Fig. 18-6). Iodine-sublimated paper, which changes color when wet, also can be used, and thermography or surface thermometers will document the temperature changes of the skin.

TREATMENT AND PROGNOSIS: Most cases are mild enough that treatment is not required. Moreover, approximately 5% of adult patients and almost all affected infants experience spontaneous resolution of the syndrome. About 5% of Frey syndrome patients with diabetically damaged kidneys will show considerable improvement or complete resolution of the facial problem after renal transplant.

Severing the auriculotemporal or glossopharyngeal nerve on the affected side inhibits or abolishes the sweating and flushing reaction of auriculotemporal syndrome, as may atropine injections, botulinum toxin injections, scopolamine creams, and the systemic use of oxybutynin chloride, an antimuscarinic agent. The risk of this syndrome is greatly diminished by positioning a temporoparietal fascia flap between the gland and the overlying skin of the cheek at the time of parotidectomy.

CLINICAL AND RADIOGRAPHIC FEATURES: Osteoarthritis usually involves multiple joints, typically the large weight-bearing joints. The disease is characterized by a gradually intensifying deep ache and pain, usually worse in the evening than in the morning. Some degree of morning joint stiffness and stiffness after inactivity is present in 80% of cases. The affected joint may become swollen and warm to the touch, rarely with erythema of the overlying skin. Degenerative changes occur in areas of greatest impact, and the joint may become so deformed that it limits motion. Crepitation (i.e., crackling noise during motion) is a late sign of the disease and is, therefore, associated with more pronounced damage.

These changes are seen also when the TMJ is affected, except that patients seldom experience stiffness of the TMJ. In addition, the muscles of mastication frequently exhibit tenderness because of the constant strain of “muscle guarding” (i.e., attempting to keep the painful joint immobile).

On radiography, joints affected by osteoarthritis demonstrate a narrowing or obliteration of the joint space, surface irregularities and protuberances (exostoses, osteophytes), flattening of the articular surface, osteosclerosis and osteolysis of bone beneath the cartilage, radiolucent subchondral cysts, and ossification within the synovial membrane (ossicles). More sensitive diagnostic techniques, such as computed tomography (CT) scanning arthrography, magnetic resonance imaging (MRI), and arthroscopy, reveal the same features but in much more detail; hence, they are able to identify earlier changes. With arthroscopy, 90% of the joints will show evidence of synovitis, usually before cartilage surface changes are visible.

HISTOPATHOLOGIC FEATURES: The articulating surface of a joint affected by osteoarthritis has a diminished number of chondrocytes, is roughened, and contains variable numbers of vertical clefts; in older cases the clefts extend to the underlying bone. The surface is proliferative in some areas and degenerative in others. The bone beneath the cartilage shows a loss of osteocytes, minimal osteoblastic or osteoclastic activity, fatty degeneration or necrosis of the marrow, marrow fibrosis, infiltration by chronic inflammatory cells, and perhaps the formation of a large degenerative space beneath the articular cartilage (subchondral cyst). Inflammation and thickening of the synovial membrane is seen, sometimes with the formation of metaplastic bone (ossicles) or hyaline cartilage granules (chondral bodies), which may number in the hundreds within a single joint. The synovial joint fluid typically contains inflammatory and degra-dation molecules, the levels of which have prognostic significance.

The TMJ is unique because of its fibrocartilage covering and its meniscus. The disk may be centrally destroyed, and there is little vertical clefting of the articular surface. All other features of TMJ osteoarthritis, however, are similar to those noted in other joints.

TREATMENT AND PROGNOSIS: The treatment of osteoarthritis is usually palliative and consists of analgesics and nonsteroidal antiinflammatory drugs (NSAIDs) for the symptoms. Arthroplasty and joint replacement often are required for heavy weight-bearing joints and are used occasionally in the TMJ. Occlusal adjustment and occlusal splints may reduce symptoms by relieving the pressure on the joint surfaces, and orofacial physiotherapy and hot or cold packs may be helpful to relax involved muscles. Arthroscopic lavage provides short-term pain relief in many cases, and low-dose doxycycline (collagenase inhibitor, antimatrix metalloproteinase) recently has been shown to reduce symptoms. Glucosamine and chondroitin sulfate, common therapies for large joint arthritis, have shown some success in TMJ osteoarthritis patients.

Aggressive therapy might not be indicated for this disease except in its most severe form. A recent 30-year follow-up investigation found radiographic evidence of continued joint destruction, but the clinical signs and symptoms were no more severe than they had been initially.

CLINICAL AND RADIOGRAPHIC FEATURES: Rheumatoid arthritis affects women three times more frequently than men, although the condition in men is usually diagnosed at a somewhat younger age (25 to 35 years) than in women (35 to 45 years). The onset and course of the disease are extremely variable. For many patients, only one or two joints become involved and significant pain or limitation of motion never develops. In others, the disease rapidly progresses to debilitating polyarthralgia.

Typically, the signs and symptoms become more severe over time and include swelling, stiffness, pain, joint deformity, and disability, with possible fibrous or bony fusion of opposing articular surfaces (ankylosis). Periods of remission often are interspersed with periods of exacerbation. Symmetrical involvement of the small joints of the hands and feet almost always is present, but it is not unusual for knees and elbows to be affected. The hip joint, the joint most often affected by osteoarthritis, is the joint least affected by rheumatoid arthritis. Twenty percent of patients have firm, partially movable, nontender rheumatoid nodules beneath the skin near the affected joint. These are pathognomonic for the disease.

Joints involved with rheumatoid arthritis have a characteristic “anvil” shape, with an irregular flattening of the central articular surface and a splaying of the lateral bone. Unlike the situation in osteoarthritis, narrowing of the joint space is seldom seen, except when ankylosis has occurred.

The TMJ is affected to some degree in more than 40% of persons with rheumatoid arthritis. When present, TMJ involvement is usually bilateral and occurs late in the disease. The signs and symptoms are seldom as severe as in other joints and include stiffness, crepitation, pain or ache, tenderness, or limitation of mouth opening. Swelling is less obvious than with other joints.

Frequently, the pain of TMJ rheumatoid arthritis is not related to motion but rather to pressure on the joint. Clenching the teeth on one side produces pain of the contralateral joint. Similarly, subluxation or ankylosis is less frequent in the TMJs than in other joints, but gross destruction of the condylar heads may be so severe that mandibular micrognathia causes a receding chin and malocclusion. Permanent TMJ subluxation has been reported.

Radiographically, involved TMJs demonstrate a flattened condylar head with irregular surface features, an irregular temporal fossa surface, perhaps with remodeling of the fossa itself, and anterior displacement of the condyle. Several diagnostic techniques are available besides routine TMJ radiographs. CT scans, scanning arthrography, and arthroscopy are excellent tools for assessing TMJ damage. Thermography is used commonly in Europe to detect early disease. Ultrasonography is valuable for larger joints but has been used little in TMJ disease. Nuclear medicine scans that use scintigraphy have, in recent years, been largely replaced by MRI scans. The latter are sensitive and have become the diagnostic tool of choice.

LABORATORY VALUES: Approximately 80% of patients with rheumatoid arthritis exhibit significant elevations of rheumatoid factor (RF), an autoantibody thought to be directed toward an altered host IgG antibody that is no longer recognized by the body as “self.” In addition, antinuclear antibodies (ANAs) can be detected in about 50% of the patients with rheumatoid arthritis, although it is not diagnostically specific because it also may be associated with other autoimmune diseases. During active phases of the disease, almost all patients have an elevated erythrocyte sedimentation rate. In addition, some affected patients have mild anemia.

HISTOPATHOLOGIC FEATURES: Needle biopsy is the most popular technique for obtaining diagnostic synovial material, but aspiration and analysis of synovial fluid from the affected joint frequently are undertaken to rule out other forms of arthritis. These techniques are seldom used for TMJ involvement.

Microscopically, early cases of rheumatoid arthritis demonstrate hyperplasia of the synovial lining cells with deeper portions of the membrane showing hyperemia, edema, and infiltration by lymphocytes, macrophages, and occasional neutrophils. Neutrophils are the predominant inflammatory cell in the synovial fluid. Older lesions show continued, often pronounced synovial proliferation and edema, with cholesterol crystals and fewer inflammatory cells. Typically, the membrane protrudes into the joint space as villi or fingerlike projections. These projections occasion-ally undergo necrosis, producing rice bodies—small whitish villi fragments composed of cellular debris admixed with fibrin and collagen. When the TMJ is severely involved, the meniscus is typically perforated or replaced completely by fibrous scar.

The rheumatoid nodule is represented by a moderately well-demarcated area of amorphous, eosinophilic necrosis surrounded by a thick layer of mononuclear cells. The mononuclear cells closest to the amorphous center are typically large and palisaded. Neutrophils are frequently seen in the center.

TREATMENT AND PROGNOSIS: No cure exists for rheumatoid arthritis, and current treatments strive only to suppress the process as much as possible. The various therapies that are used are largely empirical and aimed at nonspecific suppression of the inflammatory or immunologic process in an effort to attenuate not only the symptoms but also the progressive damage to articular structures. Drug therapy in early and mild cases consists of nonsteroidal antiinflammatory drugs (NSAIDs), perhaps aided by occasional corticosteroid injections into the joint. The latter injections are used sparingly, however, because frequent use is associated with additional degenerative changes and fibrous ankylosis.

Second-line medications often are required, and the wide variability in responses to these drugs typically results in an extended course of constantly changing doses and agents in an effort to achieve optimal relief. Systemic glucocorticoid therapy has been shown to be effective in providing symptomatic relief for patients with rheumatoid arthritis. A number of agents appear to have the capacity to modify the course of rheumatoid arthritis, and these medications are referred to as disease-modifying antirheumatic drugs. Agents such as gold injections, D-penicillamine, sulfasalazine, the antimalarials, and methotrexate are included in this group. Patients report clinical improvement with the use of these medications; they also demonstrate an improvement in serologic evidence of disease activity with reductions in C-reactive protein, erythrocyte sedimentation rate, and RF. Emerging evidence indicates that the early and aggressive use of disease-modifying antirheumatic drugs may actually retard the development of bone erosions and potentially facilitate healing of existing lesions. However, toxicity is a problem with all of these agents, and at present, no one drug has demonstrated a consistent advantage over the others. Methotrexate, a folic acid antagonist, is the most frequently used first-line agent in the disease-modifying group. The literature suggests that patients who fail or who have shown a suboptimal response to disease-modulating therapy might benefit from tumor necrosis factor-a (TNF-a) neutralizing agents (e.g., etanercept and infliximab), used alone or in combination with standard disease-modulation algorithms.

Immunosuppressive drugs such as azathioprine, cyclosporine, and cyclophosphamide appear to be no more effective in the management of rheumatoid arthritis than the previously mentioned disease-modulating antirheumatic drugs, and the side effect profile of immunosuppressive therapy includes increased risk for serious infections and potential predisposition to the development of malignant neoplasms. Therefore, immunosuppressive therapy should be reserved for those patients who have failed all other efforts at disease modulation.

Severely damaged joints may require surgical replacement, with the goals of therapy being attenuation of pain and reduction of disability. Total joint replacement of the hips, knees, and shoulders are reported to have the highest satisfaction rates associated with surgical management of these patients.

CLINICAL AND RADIOGRAPHIC FEATURES: TMD is seen primarily in middle-aged women, but it may affect any age and either sex. Most patients have some degree of pain, which is the primary reason for seeking professional help. The pain is usually localized to the preauricular area but may radiate to the temporal, frontal, or occipital areas. The pain may be a headache, a ringing in the ears (tinnitus), an earache (otalgia), or a toothache.

Nonarthritic inflammatory disorders of the TMJ are characterized by continuous deep pain or ache. The pain is evoked by palpation of the affected joint or by mandibular movement, especially chewing and clenching. Both TMJs may be involved, at the same time or at differing times.

The pain may be associated more with the surrounding musculature and soft tissue than with the TMJ itself. Muscle splinting can lead to involuntary CNS-induced muscular contractions (myospasm), or the muscle fibers themselves may become inflamed (myositis).

Myofascial trigger point pain is common in TMD, but it is seldom noted in other TMJ disorders. It is characterized by circumscribed regions within the muscle (“trigger points”) that elicit local or referred pain on palpation and may be a source of constant deep pain. In many instances, patients are aware only of the referred pain and not the trigger points themselves. The exact nature of the trigger points is not known, but they seem similar to small areas of myospasm and can, through their chronic nature, induce CNS excitatory effects.

Derangements of the condyle and meniscus complex are more often associated with dysfunction than with joint pain (arthralgia). When present, the pain associated with a deranged joint may be localized, nonspecific, or referred. It is not a reliable finding for diagnostic purposes. For TMD associated with internal joint damage or derangement, CT and MRI provide excellent diagnostic images of the TMJ. Transcranial and cephalometric radiographic images are much less detailed, but they are usually adequate and are used more commonly. The bone itself frequently appears normal, but a widened joint space, anteriorly displaced meniscus, or altered meniscus shape are common findings. Irregular joint surfaces with protuberances (osteophytes) are more likely to relate to arthritis than TMD (see previous two topics). Joint effu-sions seen with MRI are useful markers of arthritic degeneration.

TREATMENT AND PROGNOSIS: Therapies for TMD are numerous and should be recommended based on the exact pathogenesis of the pain. Conservative treatments include simple rest or immobilization of the joint, application of cold (usually reserved for acute injuries) or heat, occlusal splints and adjustment, and physical therapy. Various medications also have been used for TMD with some success (Box 18-11), although few TMD treatments have been examined in a blinded, controlled fashion. Long-term follow-up of large numbers of patients treated conservatively indicates that 75% to 88% experience significant or complete reduction of symptoms.

Surgical intervention may be required for severely affected joints, especially those with internal meniscal derangements, condylar dislocation or fracture, ankylosis, and degenerative or developmental deformities. Usually, TMD is treated conservatively for several years without improvement before surgery is attempted. For joints with pain from anterior disk displacement (with or without reduction), however, diskectomy is recommended within 6 months of TMD diagnosis; for those with ankylosis, surgery should occur even sooner. The indications for surgery are strict. Of all patients sent to a specialist for TMD surgery, fewer than 1% actually have the surgery.

CLINICAL FEATURES: TMJ ankylosis occurs predominantly in the first decade of life, and males and females are equally affected. Almost all cases are unilateral. The condition results in a gradually worsening inability to open the jaws, with the mandible shifting toward the affected side on opening. Pain, tenderness, and malocclusion may be present, but this is not usually the case.

In severe examples, there is almost complete immobilization of the mandible, and the mandible may protrude forward as the excess tissues occupy the joint space. In very young children, unilateral micrognathia (hemifacial microsomia) may result from diminished growth on the affected side. Malocclusion may be severe in such cases.

HISTOPATHOLOGIC FEATURES: TMJ ankylosis is characterized by an excessive amount of dense, rather avascular fibrous connective tissue or new bone formation. Intra-articular ankylosis demonstrates irregular destruction of cartilage and bone with a sparse lymphocytic infiltration.

TREATMENT AND PROGNOSIS: Surgical osteoplasty of the joint with removal of excessive fibrous or calcific tissues is the treatment of choice for TMJ ankylosis. For severe cases, complete joint replacement may be necessary.