Harrison's Neurology in Clinical Medicine, 3rd Edition


M. Flint Beal Image Stephen L. Hauser

Symptoms and signs of cranial nerve pathology are common in internal medicine. They often develop in the context of a widespread neurologic disturbance, and in such situations cranial nerve involvement may represent the initial manifestation of the illness. In other disorders, involvement is largely restricted to one or several cranial nerves; these distinctive disorders are reviewed in this chapter. Disorders of ocular movement are discussed in Chap. 21, disorders of hearing in Chap. 24, and vertigo and disorders of vestibular function in Chap. 11.



The trigeminal (fifth cranial) nerve supplies sensation to the skin of the face and anterior half of the head (Fig. 34-1). Its motor part innervates the masseter and pterygoid masticatory muscles.



The three major sensory divisions of the trigeminal nerve consist of the ophthalmic, maxillary, and mandibular nerves.


Clinical manifestations

Trigeminal neuralgia is characterized by excruciating paroxysms of pain in the lips, gums, cheek, or chin and, very rarely, in the distribution of the ophthalmic division of the fifth nerve. The pain seldom lasts more than a few seconds or a minute or two but may be so intense that the patient winces, hence the term tic. The paroxysms, experienced as single jabs or clusters, tend to recur frequently, both day and night, for several weeks at a time. They may occur spontaneously or with movements of affected areas evoked by speaking, chewing, or smiling. Another characteristic feature is the presence of trigger zones, typically on the face, lips, or tongue, that provoke attacks; patients may report that tactile stimuli—e.g., washing the face, brushing the teeth, or exposure to a draft of air—generate excruciating pain. An essential feature of trigeminal neuralgia is that objective signs of sensory loss cannot be demonstrated on examination.

Trigeminal neuralgia is relatively common, with an estimated annual incidence of 4.5 per 100,000 individuals. Middle-aged and elderly persons are affected primarily, and ~60% of cases occur in women. Onset is typically sudden, and bouts tend to persist for weeks or months before remitting spontaneously. Remissions may be long-lasting, but in most patients the disorder ultimately recurs.


Symptoms result from ectopic generation of action potentials in pain-sensitive afferent fibers of the fifth cranial nerve root just before it enters the lateral surface of the pons. Compression or other pathology in the nerve leads to demyelination of large myelinated fibers that do not themselves carry pain sensation but become hyperexcitable and electrically coupled with smaller unmyelinated or poorly myelinated pain fibers in close proximity; this may explain why tactile stimuli, conveyed via the large myelinated fibers, can stimulate paroxysms of pain. Compression of the trigeminal nerve root by a blood vessel, most often the superior cerebellar artery or on occasion a tortuous vein, is the source of trigeminal neuralgia in a substantial proportion of patients. In cases of vascular compression, age-related brain sagging and increased vascular thickness and tortuosity may explain the prevalence of trigeminal neuralgia in later life.

Differential diagnosis

Trigeminal neuralgia must be distinguished from other causes of face and head pain (Chap. 8) and from pain arising from diseases of the jaw, teeth, or sinuses. Pain from migraine or cluster headache tends to be deep-seated and steady, unlike the superficial stabbing quality of trigeminal neuralgia; rarely, cluster headache is associated with trigeminal neuralgia, a syndrome known as cluster-tic. In temporal arteritis, superficial facial pain is present but is not typically shocklike, the patient frequently complains of myalgias and other systemic symptoms, and an elevated erythrocyte sedimentation rate (ESR) is usually present. When trigeminal neuralgia develops in a young adult or is bilateral, multiple sclerosis (MS) is a key consideration, and in such cases the cause is a demyelinating plaque at the root entry zone of the fifth nerve in the pons; often, evidence of facial sensory loss can be found on careful examination. Cases that are secondary to mass lesions—such as aneurysms, neurofibromas, acoustic schwannomas, or meningiomas—usually produce objective signs of sensory loss in the trigeminal nerve distribution (trigeminal neuropathy, see later in the chapter).

Laboratory evaluation

An ESR is indicated if temporal arteritis is suspected. In typical cases of trigeminal neuralgia, neuroimaging studies are usually unnecessary but may be valuable if MS is a consideration or in assessing overlying vascular lesions in order to plan for decompression surgery.

TREATMENT Trigeminal Neuralgia

Drug therapy with carbamazepine is effective in ~50–75% of patients. Carbamazepine should be started as a single daily dose of 100 mg taken with food and increased gradually (by 100 mg daily in divided doses every 1–2 days) until substantial (>50%) pain relief is achieved. Most patients require a maintenance dose of 200 mg qid. Doses >1200 mg daily provide no additional benefit. Dizziness, imbalance, sedation, and rare cases of agranulocytosis are the most important side effects of carbamazepine. If treatment is effective, it is usually continued for 1 month and then tapered as tolerated. Oxcarbazepine (300–1200 mg bid) is an alternative to carbamazepine, has less bone marrow toxicity, and probably is equally efficacious. If these agents are not well tolerated or are ineffective, lamotrigine 400 mg daily or phenytoin, 300–400 mg daily, are other options. Baclofen may also be administered, either alone or in combination with an anticonvulsant. The initial dose is 5–10 mg tid, gradually increasing as needed to 20 mg qid.

If drug treatment fails, surgical therapy should be offered. The most widely used method currently is microvascular decompression to relieve pressure on the trigeminal nerve as it exits the pons. This procedure requires a suboccipital craniotomy. Based on limited data, this procedure appears to have a >70% efficacy rate and a low rate of pain recurrence in responders; the response is better for classic tic-like symptoms than for nonlancinating facial pains. In a small number of cases, there is perioperative damage to the eighth or seventh cranial nerves or to the cerebellum, or a postoperative CSF leak syndrome. Highresolution magnetic resonance angiography is useful preoperatively to visualize the relationships between the fifth cranial nerve root and nearby blood vessels.

Gamma knife radiosurgery is also utilized for treatment and results in complete pain relief in more than two-thirds of patients and a low risk of persistent facial numbness; the response is sometimes long-lasting, but recurrent pain develops over 2–3 years in half of patients. Compared with surgical decompression, gamma knife surgery appears to be somewhat less effective but has few serious complications.

Another procedure, radiofrequency thermal rhizotomy, creates a heat lesion of the trigeminal (gasserian) ganglion or nerve. It is used less often now than in the past. Short-term relief is experienced by >95% of patients; however, long-term studies indicate that pain recurs in up to one-third of treated patients. Postoperatively, partial numbness of the face is common, masseter (jaw) weakness may occur especially following bilateral procedures, and corneal denervation with secondary keratitis can follow rhizotomy for first-division trigeminal neuralgia.


A variety of diseases may affect the trigeminal nerve (Table 34-1). Most present with sensory loss on the face or with weakness of the jaw muscles. Deviation of the jaw on opening indicates weakness of the pterygoids on the side to which the jaw deviates. Some cases are due to Sjögren’s syndrome or a collagen-vascular disease such as systemic lupus erythematosus, scleroderma, or mixed connective tissue disease. Among infectious causes, herpes zoster and leprosy should be considered. Tumors of the middle cranial fossa (meningiomas), of the trigeminal nerve (schwannomas), or of the base of the skull (metastatic tumors) may cause a combination of motor and sensory signs. Lesions in the cavernous sinus can affect the first and second divisions of the trigeminal nerve, and lesions of the superior orbital fissure can affect the first (ophthalmic) division; the accompanying corneal anesthesia increases the risk of ulceration (neuro keratitis).

TABLE 34-1



Loss of sensation over the chin (mental neuropathy) can be the only manifestation of systemic malignancy. Rarely, an idiopathic form of trigeminal neuropathy is observed. It is characterized by numbness and paresthesias, sometimes bilaterally, with loss of sensation in the territory of the trigeminal nerve but without weakness of the jaw. Gradual recovery is the rule. Tonic spasm of the masticatory muscles, known as trismus, is symptomatic of tetanus or may occur in patients treated with phenothiazine drugs.



(Fig. 34-2) The seventh cranial nerve supplies all the muscles concerned with facial expression. The sensory component is small (the nervus intermedius); it conveys taste sensation from the anterior two-thirds of the tongue and probably cutaneous impulses from the anterior wall of the external auditory canal. The motor nucleus of the seventh nerve lies anterior and lateral to the abducens nucleus. After leaving the pons, the seventh nerve enters the internal auditory meatus with the acoustic nerve. The nerve continues its course in its own bony channel, the facial canal, and exits from the skull via the stylomastoid foramen. It then passes through the parotid gland and subdivides to supply the facial muscles.



The facial nerve. A, B, and C denote lesions of the facial nerve at the stylomastoid foramen, distal and proximal to the geniculate ganglion, respectively. Green lines indicate the parasympathetic fibers, red line indicates motor fibers, and purple lines indicate visceral afferent fibers (taste). (Adapted from MB Carpenter: Core Text of Neuroanatomy, 2nd ed. Baltimore, Williams & Wilkins, 1978.)

A complete interruption of the facial nerve at the stylomastoid foramen paralyzes all muscles of facial expression. The corner of the mouth droops, the creases and skinfolds are effaced, the forehead is unfurrowed, and the eyelids will not close. Upon attempted closure of the lids, the eye on the paralyzed side rolls upward (Bell’s phenomenon). The lower lid sags and falls away from the conjunctiva, permitting tears to spill over the cheek. Food collects between the teeth and lips, and saliva may dribble from the corner of the mouth. The patient complains of a heaviness or numbness in the face, but sensory loss is rarely demonstrable and taste is intact.

If the lesion is in the middle-ear portion, taste is lost over the anterior two-thirds of the tongue on the same side. If the nerve to the stapedius is interrupted, there is hyperacusis (sensitivity to loud sounds). Lesions in the internal auditory meatus may affect the adjacent auditory and vestibular nerves, causing deafness, tinnitus, or dizziness. Intrapontine lesions that paralyze the face usually affect the abducens nucleus as well, and often the corticospinal and sensory tracts.

If the peripheral facial paralysis has existed for some time and recovery of motor function is incomplete, a continuous diffuse contraction of facial muscles may appear. The palpebral fissure becomes narrowed, and the nasolabial fold deepens. Attempts to move one group of facial muscles may result in contraction of all (associated movements, or synkinesis). Facial spasms, initiated by movements of the face, may develop (hemifacial spasm). Anomalous regeneration of seventh nerve fibers may result in other troublesome phenomena. If fibers originally connected with the orbicularis oculi come to innervate the orbicularis oris, closure of the lids may cause a retraction of the mouth, or if fibers originally connected with muscles of the face later innervate the lacrimal gland, anomalous tearing (“crocodile tears”) may occur with any activity of the facial muscles, such as eating. Another facial synkinesia is triggered by jaw opening, causing closure of the eyelids on the side of the facial palsy (jaw-winking).


The most common form of facial paralysis is Bell’s palsy. The annual incidence of this idiopathic disorder is ~25 per 100,000 annually, or about 1 in 60 persons in a lifetime.

Clinical manifestations

The onset of Bell’s palsy is fairly abrupt, maximal weakness being attained by 48 h as a general rule. Pain behind the ear may precede the paralysis for a day or two. Taste sensation may be lost unilaterally, and hyper-acusis may be present. In some cases there is mild cerebrospinal fluid lymphocytosis. MRI may reveal swelling and uniform enhancement of the geniculate ganglion and facial nerve and, in some cases, entrapment of the swollen nerve in the temporal bone. Approximately 80% of patients recover within a few weeks or months. Electromyography may be of some prognostic value; evidence of denervation after 10 days indicates there has been axonal degeneration, that there will be a long delay (3 months as a rule) before regeneration occurs, and that it may be incomplete. The presence of incomplete paralysis in the first week is the most favorable prognostic sign.


In acute Bell’s palsy there is inflammation of the facial nerve with mononuclear cells, consistent with an infectious or immune cause. Herpes simplex virus (HSV) type 1 DNA was frequently detected in endoneurial fluid and posterior auricular muscle, suggesting that a reactivation of this virus in the geniculate ganglion may be responsible for most cases. Reactivation of varicella zoster virus is associated with Bell’s palsy in up to one-third of cases, and may represent the second most frequent cause. A variety of other viruses have also been implicated less commonly. An increased incidence of Bell’s palsy was also reported among recipients of inactivated intranasal influenza vaccine, and it was hypothesized that this could have resulted from the Escherichia coli enterotoxin used as adjuvant or to reactivation of latent virus.

Differential diagnosis

There are many other causes of acute facial palsy that must be considered in the differential diagnosis of Bell’s palsy. Lyme disease can cause unilateral or bilateral facial palsies; in endemic areas, 10% or more of cases of facial palsy are likely due to infection with Borrelia burgdorferi. The Ramsay Hunt syndrome, caused by reactivation of herpes zoster in the geniculate ganglion, consists of a severe facial palsy associated with a vesicular eruption in the external auditory canal and sometimes in the pharynx and other parts of the cranial integument; often the eighth cranial nerve is affected as well. Facial palsy that is often bilateral occurs in sarcoidosis and in Guillain-Barré syndrome (Chap. 46). Leprosy frequently involves the facial nerve, and facial neuropathy may also occur in diabetes mellitus, connective tissue diseases including Sjögren’s syndrome, and amyloidosis. The rare Melkersson-Rosenthal syndromeconsists of recurrent facial paralysis; recurrent—and eventually permanent—facial (particularly labial) edema; and, less constantly, plication of the tongue. Its cause is unknown. Acoustic neuromas frequently involve the facial nerve by local compression. Infarcts, demyelinating lesions of multiple sclerosis, and tumors are the common pontine lesions that interrupt the facial nerve fibers; other signs of brainstem involvement are usually present. Tumors that invade the temporal bone (carotid body, cholesteatoma, dermoid) may produce a facial palsy, but the onset is insidious and the course progressive.

All these forms of nuclear or peripheral facial palsy must be distinguished from the supranuclear type. In the latter, the frontalis and orbicularis oculi muscles are involved less than those of the lower part of the face, since the upper facial muscles are innervated by corticobulbar pathways from both motor cortices, whereas the lower facial muscles are innervated only by the opposite hemisphere. In supranuclear lesions there may be a dissociation of emotional and voluntary facial movements and often some degree of paralysis of the arm and leg, or an aphasia (in dominant hemisphere lesions) is present.

Laboratory evaluation

The diagnosis of Bell’s palsy can usually be made clinically in patients with (1) a typical presentation, (2) no risk factors or preexisting symptoms for other causes of facial paralysis, (3) absence of cutaneous lesions of herpes zoster in the external ear canal, and (4) a normal neurologic examination with the exception of the facial nerve. Particular attention to the eighth cranial nerve, which courses near to the facial nerve in the pontomedullary junction and in the temporal bone, and to other cranial nerves is essential. In atypical or uncertain cases, an ESR, testing for diabetes mellitus, a Lyme titer, angiotensin-converting enzyme and chest imaging studies for possible sarcoidosis, a lumbar puncture for possible Guillain-Barré syndrome, or MRI scanning may be indicated. MRI often shows swelling and enhancement of the facial nerve in idiopathic Bell’s palsy (Fig. 34-3).




Axial and coronal T1-weighted images post-Gadolinium with fat suppression demonstrate diffuse smooth linear enhancement of the left facial nerve, involving the genu, tympanic, and mastoid segments within the temporal bone (arrows), without evidence of mass lesion. Although highly suggestive of Bell’s palsy, similar findings may be seen with other etiologies such as Lyme disease, sarcoidosis, and peri-neural malignant spread.

TREATMENT Bell’s Palsy

Symptomatic measures include (1) the use of paper tape to depress the upper eyelid during sleep and prevent corneal drying, and (2) massage of the weakened muscles. A course of glucocorticoids, given as prednisone 60–80 mg daily during the first 5 days and then tapered over the next 5 days, modestly shortens the recovery period and improves the functional outcome. Although two large recently published randomized trials found no added benefit of antiviral agents valacyclovir (1000 mg daily for 5–7 days) or acyclovir (400 mg five times daily for 10 days) compared to glucocorticoids alone, the overall weight of evidence suggests that the combination therapy with prednisone plus valacyclovir may be marginally better than prednisone alone, especially in patients with severe clinical presentations.


Hemifacial spasm consists of painless irregular involuntary contractions on one side of the face. Most cases appear related to vascular compression of the exiting facial nerve in the pons. Other cases develop as a sequela to Bell’s palsy or are secondary to compression and/or demyelination of the nerve by tumor, infection or multiple sclerosis. Mild cases can be treated with carbamazepine, gabapentin, or, if these drugs fail, with baclofen. Local injections of botulinum toxin into affected muscles can relieve spasms for 3–4 months, and the injections can be repeated. Refractory cases due to vascular compression usually respond to surgical decompression of the facial nerve. Blepharospasm is an involuntary recurrent spasm of both eyelids that usually occurs in elderly persons as an isolated phenomenon or with varying degrees of spasm of other facial muscles. Severe, persistent cases of blepharospasm can be treated by local injection of botulinum toxin into the orbicularis oculi. Facial myokymia refers to a fine rippling activity of the facial muscles; it may be caused by multiple sclerosis or follow Guillain-Barré syndrome (Chap. 46).

Facial hemiatrophy occurs mainly in women and is characterized by a disappearance of fat in the dermal and subcutaneous tissues on one side of the face. It usually begins in adolescence or early adult years and is slowly progressive. In its advanced form, the affected side of the face is gaunt, and the skin is thin, wrinkled, and brown. The facial hair may turn white and fall out, and the sebaceous glands become atrophic. Bilateral involvement may occur. A limited form of systemic sclerosis (scleroderma) may be the cause of some cases. Treatment is cosmetic, consisting of transplantation of skin and subcutaneous fat.



This form of neuralgia involves the ninth (glossopharyngeal) and sometimes portions of the tenth (vagus) cranial nerves. It resembles trigeminal neuralgia in many respects but is much less common. The pain is intense and paroxysmal; it originates on one side of the throat, approximately in the tonsil-lar fossa. In some cases the pain is localized in the ear or may radiate from the throat to the ear because of involvement of the tympanic branch of the glossopharyngeal nerve. Spasms of pain may be initiated by swallowing or coughing. There is no demonstrable motor or sensory deficit; the glossopharyngeal nerve supplies taste sensation to the posterior third of the tongue and, together with the vagus nerve, sensation to the posterior pharynx. Cardiac symptoms—brady-cardia or asystole, hypotension, and fainting—have been reported. Medical therapy is similar to that for trigeminal neuralgia, and carbamazepine is generally the first choice. If drug therapy is unsuccessful, surgical procedures—including microvascular decompression if vascular compression is evident—or rhizotomy of glossopharyngeal and vagal fibers in the jugular bulb is frequently successful.

Very rarely, herpes zoster involves the glossopharyngeal nerve. Glossopharyngeal neuropathy in conjunction with vagus and accessory nerve palsies may also occur with a tumor or aneurysm in the posterior fossa or in the jugular foramen. Hoarseness due to vocal cord paralysis, some difficulty in swallowing, deviation of the soft palate to the intact side, anesthesia of the posterior wall of the pharynx, and weakness of the upper part of the trapezius and sternocleidomastoid muscles make up the jugular foramen syndrome (Table 34-2).

TABLE 34-2





When the intracranial portion of one vagus (tenth cranial) nerve is interrupted, the soft palate droops ipsi-laterally and does not rise in phonation. There is loss of the gag reflex on the affected side, as well as of the “curtain movement” of the lateral wall of the pharynx, whereby the faucial pillars move medially as the palate rises in saying “ah.” The voice is hoarse and slightly nasal, and the vocal cord lies immobile midway between abduction and adduction. Loss of sensation at the external auditory meatus and the posterior pinna may also be present.

The pharyngeal branches of both vagal nerves may be affected in diphtheria; the voice has a nasal quality, and regurgitation of liquids through the nose occurs during the act of swallowing.

The vagus nerve may be involved at the meningeal level by neoplastic and infectious processes and within the medulla by tumors, vascular lesions (e.g., the lateral medullary syndrome), and motor neuron disease. This nerve may be involved by infection with varicella zoster virus. Polymyositis and dermatomyositis, which cause hoarseness and dysphagia by direct involvement of laryngeal and pharyngeal muscles, may be confused with diseases of the vagus nerves. Dysphagia is also a symptom in some patients with myotonic dystrophy.

The recurrent laryngeal nerves, especially the left, are most often damaged as a result of intrathoracic disease. Aneurysm of the aortic arch, an enlarged left atrium, and tumors of the mediastinum and bronchi are much more frequent causes of an isolated vocal cord palsy than are intracranial disorders. However, a substantial number of cases of recurrent laryngeal palsy remain idiopathic.

When confronted with a case of laryngeal palsy, the physician must attempt to determine the site of the lesion. If it is intramedullary, there are usually other signs, such as ipsilateral cerebellar dysfunction, loss of pain and temperature sensation over the ipsilateral face and contralateral arm and leg, and an ipsilateral Horner syndrome. If the lesion is extramedullary, the glossopharyngeal and spinal accessory nerves are frequently involved (jugular foramen syndrome). If it is extracranial in the posterior laterocondylar or retroparotid space, there may be a combination of ninth, tenth, eleventh, and twelfth cranial nerve palsies and a Horner syndrome (Table 34-2). If there is no sensory loss over the palate and pharynx and no palatal weakness or dysphagia, the lesion is below the origin of the pharyngeal branches, which leave the vagus nerve high in the cervical region; the usual site of disease is then the mediastinum.


Isolated involvement of the accessory (eleventh cranial) nerve can occur anywhere along its route, resulting in partial or complete paralysis of the sternocleidomastoid and trapezius muscles. More commonly, involvement occurs in combination with deficits of the ninth and tenth cranial nerves in the jugular foramen or after exit from the skull (Table 34-2). An idiopathic form of accessory neuropathy, akin to Bell’s palsy, has been described, and it may be recurrent in some cases. Most but not all patients recover.


The hypoglossal (twelfth cranial) nerve supplies the ipsi-lateral muscles of the tongue. The nucleus of the nerve or its fibers of exit may be involved by intramedullary lesions such as tumor, poliomyelitis, or most often motor neuron disease. Lesions of the basal meninges and the occipital bones (platybasia, invagination of occipital condyles, Paget’s disease) may compress the nerve in its extramedullary course or in the hypoglossal canal. Isolated lesions of unknown cause can occur. Atrophy and fasciculation of the tongue develop weeks to months after interruption of the nerve.


Several cranial nerves may be affected by the same disease process. In this situation, the main clinical problem is to determine whether the lesion lies within the brainstem or outside it. Lesions that lie on the surface of the brainstem are characterized by involvement of adjacent cranial nerves (often occurring in succession) and late and rather slight involvement of the long sensory and motor pathways and segmental structures lying within the brainstem. The opposite is true of primary lesions within the brainstem. The extramedullary lesion is more likely to cause bone erosion or enlargement of the foramens of exit of cranial nerves. The intramedullary lesion involving cranial nerves often produces a crossed sensory or motor paralysis (cranial nerve signs on one side of the body and tract signs on the opposite side).

Involvement of multiple cranial nerves outside the brainstem is frequently the result of trauma, localized infections including varicella zoster virus, infectious and noninfectious (especially carcinomatous) causes of meningitis (Chaps. 40 and 41), granulomatous diseases such as granulomatosis with polyangiitis (Wegener’s), Behçet’s disease, vascular disorders including those associated with diabetes, enlarging saccular aneurysms, or locally infiltrating tumors. Among the tumors, nasopharyngeal cancers, lymphomas, neurofibromas, meningiomas, chordomas, cholesteatomas, carcinomas, and sarcomas have all been observed to involve a succession of lower cranial nerves. Owing to their anatomic relationships, the multiple cranial nerve palsies form a number of distinctive syndromes, listed in Table 34-2. Sarcoidosis is the cause of some cases of multiple cranial neuropathy, and chronic glandular tuberculosis the cause of a few others. Platybasia, basilar invagination of the skull, and the Chiari malformation are additional causes. A purely motor disorder without atrophy always raises the question of myasthenia gravis (Chap. 47). As noted earlier, Guillain-Barré syndrome commonly affects the facial nerves bilaterally. In the Fisher variant of the Guillain-Barré syndrome, oculomotor paresis occurs with ataxia and areflexia in the limbs (Chap. 46). Wernicke encephalopathy can cause a severe ophthalmoplegia combined with other brainstem signs (Chap. 28).

The cavernous sinus syndrome (Fig. 34-4) is a distinctive and frequently life-threatening disorder. It often presents as orbital or facial pain; orbital swelling and chemosis due to occlusion of the ophthalmic veins; fever; oculomotor neuropathy affecting the third, fourth, and sixth cranial nerves; and trigeminal neuropathy affecting the ophthalmic (V1) and occasionally the maxillary (V2) divisions of the trigeminal nerve. Cavernous sinus thrombosis, often secondary to infection from orbital cellulitis (frequently Staphylococcus aureus), a cutaneous source on the face, or sinusitis (especially with mucormycosis in diabetic patients), is the most frequent cause; other etiologies include aneurysm of the carotid artery, a carotid-cavernous fistula (orbital bruit may be present), meningioma, nasopharyngeal carcinoma, other tumors, or an idiopathic granulomatous disorder (Tolosa-Hunt syndrome). The two cavernous sinuses directly communicate via intercavernous channels; thus, involvement on one side may extend to become bilateral. Early diagnosis is essential, especially when due to infection, and treatment depends on the underlying etiology.



Anatomy of the cavernous sinus in coronal section, illustrating the location of the cranial nerves in relation to the vascular sinus, internal carotid artery (which loops anteriorly to the section), and surrounding structures.

In infectious cases, prompt administration of broad-spectrum antibiotics, drainage of any abscess cavities, and identification of the offending organism are essential. Anticoagulant therapy may benefit cases of primary thrombosis. Repair or occlusion of the carotid artery may be required for treatment of fistulas or aneurysms. The Tolosa-Hunt syndrome generally responds to glucocorticoids. A dramatic improvement in pain is usually evident within a few days; oral prednisone (60 mg daily) is usually continued for 2 weeks and then gradually tapered over a month, or longer if pain recurs.

An idiopathic form of multiple cranial nerve involvement on one or both sides of the face is occasionally seen. The syndrome consists of a subacute onset of boring facial pain, followed by paralysis of motor cranial nerves. The clinical features overlap those of the Tolosa-Hunt syndrome and appear to be due to idiopathic inflammation of the dura mater, which may be visualized by MRI. The syndrome is frequently responsive to glucocorticoids.