The trigeminal ganglion (Gasserian or semilunar ganglion) is the sensory ganglion that contains the nerve cell bodies of the pseudounipolar neurons of the sensory root of the trigeminal nerve. The trigeminal ganglion is located in Meckel’s cave near the apex of the petrous part of the temporal bone just behind the internal carotid artery and the posterior portion of the cavernous sinus.¹ Proximally, the sensory root enters the pons and terminates in the trigeminal nuclei (which receive input from all sensory nerves innervating the face). From rostral to caudal, the trigeminal nuclei are divided into three parts: mesencephalic nucleus (in the midbrain and pons), principal sensory nucleus (in the pons), and spinal nucleus (spanning the pons to the upper cervical cord) (Fig. 36.1).

The mesencephalic nucleus receives muscle spindle information conveying proprioceptive afferents from the muscles of mastication. These are the only primary sensory afferents that have their cell body in the CNS, rather than outside in a sensory ganglion. A collateral branch synapses directly on the motor nucleus of the trigeminal nerve to activate jaw closure through the monosynaptic jaw jerk reflex. However, it also sends projections to the principal sensory nucleus and the spinal nucleus.

The principal sensory nucleus is thought to mediate large fiber modalities such as fine touch or other proprioceptive afferents. The spinal nucleus is thought to mediate small fiber modalities such as pain and temperature. The long spinal nucleus is organized in a somatopic fashion, with the most rostral region receiving innervation from the most midline regions (the mouth and nose), whereas the most caudal region receiving innervation from the most dorsal regions (outer ears). Therein lays the onionskin somatotopic organization of the spinal nucleus.² Furthermore, the spinal nucleus receives proprioceptive information from mesencephalic nucleus projections.

Most of the fibers from the principal sensory and spinal nuclei cross to the contralateral side and ascend in the anterior trigeminothalamic tract to the ventral posteromedial nucleus of the thalamus. The anterior trigeminothalamic tract joins lateral to the medial lemniscus, which carries the analogous sensory fibers from the contralateral body to the ventral posterolateral nucleus of the thalamus. From the thalamus, the secondary neurons project to the primary somatosensory cortex located in the postcentral gyrus of the parietal lobe. There is much overlap of somatotopy of the face in the thalamus, while the inverted facial somatotopy is relatively more preserved in the primary somatosensory cortex (S1 region). From the superior-to-inferior axis in the coronal plane of the postcentral gyrus, the representation of the thumb is the more superior, followed by the most caudal facial region V1, than the more rostral facial regions. Muscle spindle information from the mesencephalic nucleus projects to the cerebellum.

The motor nucleus is ventral and medial to the principal sensory nucleus in the midpons. The motor root exits midpons and is anterior and medial to the larger sensory root. In Meckel’s cave, the motor root travels below the trigeminal ganglion and exits the skull through the foramen ovale along with the mandibular division. The motor nucleus receives input from sensory branches of the trigeminal and other sensory cranial nerves. It also receives input from bilateral motor cortex for voluntary control of chewing.

The three sensory divisions of the trigeminal nerve are the ophthalmic (V₁), maxillary (V₂), and mandibular (V₃) (see Figs. 36.2 and 36.3). Although autonomic fibers do not originate from the trigeminal nerve, parasympathetic fibers from CN III (oculomotor), VII (facial), and IX (glossopharyngeal) and sympathetic fibers from superior 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 pain-sensitive structures in the body. Sensitivity is greatest in the center of the cornea and decreases toward the limbus. Pain receptors are also found in extraocular muscle, conjunctiva, uvea, sclera, and optic nerve sheath. In contrast, the retina, optic nerve, and lens are devoid of pain receptors.

Several trigeminal reflexes are of clinical importance. Pressure, or manipulation, of the ocular structures can result in the oculocardiac reflex, which is responsible for the bradycardia and other arrhythmias seen in ocular surgery, in particular strabismus surgery.³ The oculocardiac reflex, however, is only a portion of the broader trigeminocardiac reflex in which the afferent limb of the reflex is the trigeminal nerve, and the efferent limb is the vagus nerve.^4,5 Vagal stimulation of 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 corneal, corneolacrimal (reflex tearing), corneomandibular, and corneo-oculogyric reflexes.⁶ Nausea and vomiting may occur during an acute attack of glaucoma, with trauma, or with 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 pinprick. The dermatomes of each of the three divisions of the trigeminal nerve should be tested separately (see Fig. 36.3). Temperature, vibration, stereognosis, and twopoint discrimination can also be assessed, but have little clinical relevance.

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 (medial pterygoids) and lateral movement against resistance (lateral pterygoids). 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 CN X function.

A unilateral supranuclear lesion rarely causes any weakness of the masticatory muscles because of bilateral cortical innervation of the trigeminal motor nuclei. 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 disease. Mouth retraction and jaw opening or closing may be seen in Meige 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 (jaw/ear pain while chewing) is a frequent complaint in giant cell arteritis. Spasm of the masticatory muscles, with inability to open the mouth, is called trismus and can be seen in hemimasticatory spasm, tetanus, encephalitis, strychnine poisoning, and hysteria.

Corneal disease can be secondary to a lesion of the trigeminal nerve impairing cutaneous sensation in the ophthalmic division. Corneal nerve fibers and the corneal epithelium exert mutualistic trophic influences on each other with the trigeminal nerves secreting neurotransmitters and neuropeptides (such as substance P and calcitonin gene-related peptide) that maintain tissue integrity, physiologic renewal, and wound healing.

Corneal nerve fiber loss may occur iatrogenically from surgery (for trigeminal neuralgia or acoustic neuroma), medication effect (topical), diabetes, or infections (especially herpes simplex virus or herpes zoster).¹¹ Photorefractive keratectomy and laser-assisted in situ keratomileusis (LASIK) are the newest iatrogenic causes of corneal nerve fiber loss.¹² Loss of corneal sensation almost always accompanies trigeminal nerve lesions that impair cutaneous sensation in the ophthalmic division.¹³ Neurotrophic keratitis is the inflammation or loss of corneal epithelium associated with the loss of corneal nerve fibers (Fig. 36.6). The loss of trophic support from the corneal nerve fibers is thought to be a major factor, and much research is directed at developing treatment with neuropeptides to prevent this disease. However, other factors are thought to contribute, including desiccation of corneal surface due to diminished lacrimation, environmental exposure, inappropriate contact lens use, impaired corneal sensitivity, and therefore decreased protective blink reflexes and abnormal epithelial cell metabolism.

Treatment includes topical lubrication, punctal occlusion, environmental protective measures, and discontinuing topical ocular therapies that can decrease corneal sensitivity (e.g., timolol, betaxolol, sulfacetamide, diclofenac, ketorolac). Surgery may be needed to (1) close the eyelid (which can be by lateral tarsorrhaphy or botulinum A toxin injection into the levator muscle), (2) repair of corneal perforation or descemetocele secondary to severe stromal ulcerations, and (3) treatment of persistent epithelial defect. The second goal can be accomplished by amniotic membrane grafts.^14,15,16

Peripheral branches of the trigeminal nerve can be affected by numerous disease processes, including traumatic, vascular, inflammatory, demyelinating, infectious, or neoplastic processes.¹⁷ Facial trauma may impair branches of any of the three divisions, but most often damaged are the infraorbital, supratrochlear, and supraorbital nerves (see Fig. 36.3).¹⁸ Dental procedures are a common cause of trigeminal neuropathy, because the dental nerves course in the maxilla and mandible at the same depth as the roots of the teeth.^19,20 Specifically, removal of the lower third molar can cause damage to the inferior alveolar nerve (innervating the lower teeth, lower lip, and chin) and the lingual nerve (tongue) at a rate of approximately 4%.²¹ The LASIK procedure has been reported to cause infraorbital nerve damage.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.¹⁹

Trigeminal pain and numbness are rarely the first sign of tumors of the nasopharynx, paranasal sinuses, oral cavity, and orbit. Nasopharyngeal carcinoma has a tendency to spread perineurally from the cavernous sinus,²⁴ as can adenoid cystic carcinomas and dermatologic malignancies.²⁵ Sensory loss in orbital disease of all causes is relatively uncommon, occurring in only approximately 3% of the patients.²⁶ Patients rarely complained of subjective numbness, approximately half complained of pain. This is also true in patients with orbital malignancies. Carcinomatous leptomeningitis can present with cranial neuropathies.²⁷ Amyloidomas are also in the differential.²⁸

Trigeminal neuropathy can be a sequela of autoimmune connective tissue and inflammatory disease (such as undifferentiated and mixed connective tissue diseases, scleroderma,²⁹ Sjögren syndrome,³⁰ and progressive systemic sclerosis³¹). Chronic immune-mediated demyelinating polyneuropathy (CIDP) or acute immune-mediated demyelinating polyneuropathy (Guillain-Barré syndrome) can also have trigeminal neuropathies present (albeit mostly subclinical in CIDP).³² Corticosteroids are not thought to provide symptomatic relief in Sjögren syndrome.^30,33

Infectious etiologies include leprosy,^34,35 Lyme disease,³⁶ neurosyphilis,^37,38 and mucormycosis.³⁹

In approximately 10% of cases, facial numbness occurs as a self-limited entity of unknown etiology.^40,41,42,43 The term “trigeminal sensory neuropathy” is used by some authors to indicate this disease; however, the term is used nebulously and can be used to describe conditions that are also 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,⁴² 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.^41,43,44 The main differential is tumor, and there may be transient abnormalities of the trigeminal nerve on MRI, furthering the confusion.⁴⁵ 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.^46,47 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, but the EMG does not typically 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 associates⁴⁸ 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,⁴⁹ as can metastatic carcinomas.⁵⁰

Inflammation in the cavernous sinus has been called the Tolosa-Hunt syndrome.^51,52,53 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 the 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.^52,54 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 Beal⁵² 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.^55,56

Cavernous hemangiomas may occur at Meckel’s cave and along the trigeminal nerve.⁵⁵ V₁ and V₂ are usually involved; however, V₃ is rarely involved and thought to be related to engorgement of the inferior petrosal sinus and vascular compression at the foramen ovale.⁵⁷

Facial pain occurring with an oculosympathetic paresis is termed Raeder’s paratrigeminal neuralgia syndrome.⁵⁸ When this is associated with ocular motor nerve involvement, a mass lesion is usually present in the middle cranial fossa.

The trigeminal ganglion can be affected by infection or tumor. It is frequently the latent reservoir for the neurotropic herpes family reservoir with herpes simplex virus/human herpes virus 1 (HSV/HHV) reactivating to cause herpes labialis and varicella zoster virus/human herpes virus 3 reactivating to cause herpes zoster ophthalmicus. By age 50, 80% to 90% of the population harbors HSV-1.⁷ Herpes zoster ophthalmicus behaves like zoster infections elsewhere in the body. The incidence is increased in the aged and immunosuppressed. 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.^59,60 In 1865, Hutchinson⁶¹ noted that when the nasociliary branch to the tip of the nose is affected, intraocular involvement is likely. Vesicular lesions at the tip, side, root of the nose, representing the external nasal and infratrochlear branches of the nasociliary nerve, are associated with ocular changes and corneal denervation.⁶² Ocular changes include conjunctivitis, episcleritis, scleritis, keratitis, iritis, chorioretinitis, optic neuropathy, glaucoma, ocular motor palsies, and Horner syndrome.^59,63,64 On rare occasions, a contralateral hemiplegia may occur (Fig. 36.7).^59,65,66,67 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.