The trigeminal nerve contains both a sensory and a motor root. The cell bodies of the sensory portion lie in the gasserian (or semilunar) ganglion, with the exception of those for muscle spindle information, which lie in the mesencephalic nucleus in the midbrain. The gasserian ganglion is located in Meckel’s cave near the petrous tip of the temporal bone just behind the internal carotid and the posterior portion of the cavernous sinus. Proximally, the sensory root extends to the pons, where the fibers enter the main sensory nucleus, the nucleus of the spinal tract, and the mesencephalic nucleus (Figs. 1 and 2). The classic teaching that the nucleus of the spinal tract mediates pain and temperature sensation while the main sensory nucleus mediates fine touch is probably an oversimplification; still, the functional organization of the nuclei is not well understood.¹

The mesencephalic nucleus has special distinction because it is the only example in which sensory cell bodies lie within the central nervous system, rather than outside in a sensory ganglion. A collateral branch synapses directly on the motor nucleus of the trigeminal nerve, mediating a monosynaptic reflex for the jaw jerk.

Most of the fibers from the main sensory and spinal tract nuclei cross to the contralateral side and, in a situation analogous to the sensory fibers coming from the spinal cord, travel in the medial lemniscus and trigeminothalamic tract to the ventral posterior nucleus of the thalamus. From there, information is projected to the postcentral gyrus of the parietal lobe. Muscle spindle information from the mesencephalic nucleus projects to the cerebellum.

The motor nucleus of the trigeminal nerve is located in the midpons, and its fibers pass beneath the gasserian ganglion to join the mandibular branch of the fifth nerve to supply the muscles of mastication.

The three sensory divisions of the trigeminal nerve are the ophthalmic (V₁), maxillary (V₂), and mandibular (V₃) (see Fig. 2; Fig. 3). Although autonomic fibers do not originate from the trigeminal nerve, parasympathetic fibers from cranial nerves three (oculomotor), seven (facial), and nine (glossopharyngeal), and sympathetic fibers from cervical ganglia, travel with the widely distributed trigeminal nerve to reach their destination.

Because of its high concentration of free nerve endings, the cornea is one of the most sensitive pain structures in the body. Sensitivity to pain is greatest in the center of the cornea and decreases toward the limbus. Pain receptors are also found in the extraocular muscles, conjunctiva, uvea, sclera, and optic nerve sheaths. The retina, optic nerve, and lens, however, are devoid of pain sensitivity.¹

Several trigeminal reflexes are of clinical importance. It has been known for many years that pressure, or manipulation of, the ocular structures will cause bradycardia. This is usually called the oculocardiac reflex and is responsible for the bradycardia and other arrhythmias seen in ocular surgery, in particular, strabismus surgery.⁵ The oculocardiac reflex, however, is only a portion of the broader trigeminocardiac reflex in which the afferent limb of the reflex is by way of a branch of the trigeminal nerve, and the efferent limb is by way of the vagus nerve.^6,7 Vagal stimulation on the heart causes slowing and, rarely, asystole.

Other reflexes involving the trigeminal nerve include the jaw jerk, snout reflex, and sneeze reflex. Corneal stimulation can produce the corneolacrimal (reflex tearing), corneomandibular, and corneooculogyric reflexes.⁸ Nausea and vomiting may occur during an acute attack of glaucoma or certain intraorbital inflammatory processes.

Corneal sensitivity is tested by the light touch of a cotton-tipped applicator drawn to a fine point. If local cornea disease is present, each quadrant should be assessed separately, because it may be only a portion of the cornea that is denervated; otherwise, it is sufficient to test just the inferior cornea. The response to corneal stimulation is assessed both subjectively through the patient’s report and objectively by observation of the corneal reflex.

Cutaneous sensation is assessed as it is elsewhere in the body by testing light touch with cotton and pain with pin prick. The dermatomes of each of the three divisions of the trigeminal nerve should be tested separately (see Fig. 3). Temperature, vibration, stereognosis, and two-point discrimination can also be demonstrated, but this is usually an unnecessary procedure.

The motor root of the trigeminal nerve is assessed by palpating the temporal and masseter muscles as the patient clenches his or her jaw, and noting pterygoid strength during jaw opening and lateral movement against resistance. Weakness of the pterygoids will produce a deviation of the jaw to the ipsilateral side when the patient opens their mouth. Observation may reveal a more prominent zygomatic arch on the symptomatic side due to muscle wasting. Although more difficult to see, flattening or depression of one side of the palate and deviation of the uvula to the other side at rest may indicate tensor veli palatini dysfunction. Elevation of the palate voluntarily or to gag, however, is mostly a tenth cranial nerve function.

A unilateral supranuclear lesion rarely causes any weakness of the muscles of mastication because cortical innervation of the trigeminal motor nuclei is bilateral. An increased jaw jerk, evaluated by tapping over a finger placed on the middle of the chin with a reflex hammer while the patient relaxes his or her jaw, can be seen in supranuclear lesions. Normally, the jaw jerk is mild or absent in the nondisease state.

Observation for involuntary movements of the jaw is important. Rhythmic jaw tremor can be seen in both essential tremor and Parkinson’s disease. Mouth retraction and jaw opening or closing may be seen in Meige’s syndrome (see elsewhere in these volumes). Fatigable weakness of the jaw, or a history that the patient has to use his or her hand to close the jaw, is a feature of myasthenia gravis. A history of clonic jaw activity or chewing movements may indicate seizure activity. Jaw claudication is a frequent complaint in temporal arteritis. Spasms of the muscles of mastication are called trismus and can be seen in hemimasticatory spasm, tetanus, encephalitis, strychnine poisoning, and hysteria.

Corneal sensation is almost always decreased when a lesion of the trigeminal nerve impairs cutaneous sensation in the ophthalmic division. Direct ocular impairment from surgery, medications, corneal dystrophy, and infection can result in isolated loss of corneal sensation.¹⁵

Neuroparalytic keratitis or widespread loss of corneal epithelium may occur in an eye that becomes denervated (Fig. 6). The etiology of the keratopathy is unknown, but it is presumed that loss of sensory innervation impairs corneal nutrition, surface maintenance, and repair.^16,17 The keratopathy may respond poorly to artificial tear preparation and bandage soft contact lenses, but often the epithelial defect will heal after a tarsorrhaphy, which better protects the corneal epithethelium.¹⁸

Peripheral branches of the trigeminal nerve can be affected by numerous disease processes. Facial trauma may impair branches of any of the three divisions, but most often the infraorbital, supratrochlear, and supraorbital nerves are damaged (see Fig. 3).¹⁹ Dental procedures are an important cause of trigeminal neuropathy, because the dental nerves course in the maxilla and mandible at the same depth as the roots of the teeth.^20,21 Removal of the lower third molar deserves particular note.

Trigeminal pain and numbness are rarely the first sign of tumors of the nasopharynx, paranasal sinuses, oral cavity, and orbit. One retrospective review of 103 cases of orbital disease from all causes found sensory loss in only 3% of the patients.²²

The usual presentation of trigeminal neuropathy is either anesthesia or paresthesias, but after partial regeneration of the nerve, pain may also occur.²³ Even after the inciting cause is removed, return of function is not guaranteed. With trauma, as few as 50% will recover by 12 weeks, with a minority of the rest recovering by 2 years.²¹

In approximately 10% of cases, facial numbness occurs as a self-limited entity of unknown etiology.^24,25,26,27 The term trigeminal sensory neuropathy is used by some authors to indicate this disease, whereas others mean something more broad by trigeminal sensory neuropathy, including conditions that are painful. The second and third trigeminal divisions are affected most often, and a sensory deficit can usually be detected in the involved dermatome. This condition is only rarely bilateral. Trigeminal motor function is typically normal. Involvement of the peripheral trigeminal branches is most likely the cause,²⁵ and many authors have made an analogy with Bell’s palsy. Most patients recover sensory function over a period of a few weeks to months, but it may be recurrent. A diagnosis of idiopathic facial numbness should not be made until a thorough investigation is undertaken.^26,27,28 The main differential is tumor, and there may be transient abnormalities of the trigeminal nerve on magnetic resonance imaging (MRI), furthering the confusion.²⁹ The etiology usually remains in question until the patient shows improvement. If no improvement occurs, frequent clinical evaluations are recommended to detect a pathologic process early.

Hemimasticatory spasm is a condition of unilateral involuntary jaw closure that is often associated with facial hemiatrophy, but not always.^30,31 The contractions may be prolonged but are usually brief, resembling hemifacial spasm. The spasms are painful, and patients may break teeth, develop temporomandibular joint disease, or bite their tongue. Electrodiagnostic investigations have demonstrated peripheral motor nerve demyelination. The EMG does not show denervation. Ephaptic transmission, which refers to the concept of an artificial synapse between contiguous nerves caused by the lateral spread of extraaxonal current through the interstitium, is one possible mechanism. Treatment includes botulinum toxin and carbamazepine, which is the most successful oral medication.

Masses or inflammation in the superior orbital fissure or cavernous sinus may affect the ophthalmic and maxillary divisions of the trigeminal nerve as well as the oculomotor, trochlear, abducens, and sympathetic nerves. Trobe and associates³² reported pain and impaired sensation in one of seven patients with meningiomas and in four of nine with aneurysms in the cavernous sinus. Trigeminal neurinoma or schwannoma can occur anywhere along the nerve and has also been reported in the cavernous sinus.³³

Inflammation in the cavernous sinus has been called the Tolosa-Hunt syndrome.^34,35,36 Pain is a prominent feature and may precede signs of involvement of the other nerves. It is typically described as a constant “boring” ache behind the eye. Loss of sensation in the ophthalmic more than the maxillary dermatomes is frequent. Corticosteroids can help with both pain and the speed of cranial nerve recovery. In a related condition called orbital pseudotumor, the inflammation occurs more anteriorly in the actual orbit, rather than in the cavernous sinus. The distinction between Tolosa-Hunt syndrome and orbital pseudotumor may be difficult to make; the underlying immunopathologic deficit perhaps being the same.

Cranial polyneuropathy is a condition of multiple cranial nerve palsies.^36,37 Involvement is not limited just to the cavernous sinus, as in the Tolosa-Hunt syndrome. The abducens nerve is the one most often affected, but any combination is possible, with the exception of the olfactory nerve. Causes include the Guillain-Barré syndrome, infections, tumors, carcinomatous meningitis, sarcoidosis, collagen vascular disease, and idiopathic causes. A retrospective review by Juncos and Beal³⁶ found the trigeminal nerve to be involved in 5 of 14 cases of idiopathic cranial polyneuropathy they analyzed. Face and head pain were almost invariable, and corticosteroids provided symptomatic benefit.

Tumors at the base of the skull (chondroma, sarcoma, chordoma, meningioma, and nasopharyngeal tumors) can involve the trigeminal nerve, producing pain or a sensory deficit. In most cases, other cranial nerves are also affected.

Facial pain occurring with an oculosympathetic paresis is termed Raeder’s paratrigeminal neuralgia syndrome.³⁸ When this is associated with ocular motor nerve involvement, a mass lesion is usually present in the middle cranial fossa. This syndrome is discussed in more detail later in the section on Facial Pain.

The gasserian ganglion can be affected by infection or tumor. It is a frequent site of varicella zoster reactivation, and the ophthalmic division is most commonly involved.

Herpes zoster ophthalmicus behaves like zoster infections elsewhere in the body. The incidence increases with age. Pain, often severe, may precede, be concurrent with, or follow the vesicular skin eruption. Occasionally no skin lesions occur; this is referred to as zoster sine herpete. The vesicular eruption usually involves only one dermatome, but severe systemic eruptions can occur (the latter appear most often in immunocompromised persons or in persons with malignancy). Fever, malaise, headache, and lymphadenopathy may be present at the onset. Fifty percent of cases have ocular involvement, which can be predicted if vesicles appear on the lid margin or if Hutchinson’s sign is present.^39,40 In 1886, Hutchinson noted that when the nasociliary branch to the tip of the nose is affected, intraocular involvement is likely. Ocular changes include conjunctivitis, episcleritis, scleritis, keratitis, iritis, chorioretinitis, optic neuropathy, glaucoma, ocular motor palsies, and Horner’s syndrome.^39,41,42 On rare occasions, a contralateral hemiplegia may occur (Fig. 7).^39,43,44,45 A virus-induced angiitis of cerebral vessels has been shown by angiography and pathology in several cases. Although patients with neoplastic or other debilitating diseases are predisposed to the development of herpes zoster infections, a neoplasm is discovered in less than 1% of otherwise healthy persons with cutaneous zoster.