Anatomy

The disease is thought to result from compression of the trigeminal fibers as they pass from the brainstem to the face. Sites of nerve compression can be divided into brainstem, prepontine, cavernous sinus or Meckel’s cave, and extracranial. Central nervous system causes of trigeminal neuralgia include multiple sclerosis, in which plaques of demyelination can affect exiting pontine fibers.

The most frequently affected site is the trigeminal nerve root entry zone—the point at which the transition from central to peripheral myelin occurs. There, tortuous or aberrant vessels can compress the nerve. Indeed, vascular compression is thought to account for 80% to 90% of cases. The nerve then passes into the prepontine fossa, where it is vulnerable to ectasias of the basilar or vertebral arteries. Tumors of the cerebellopontine angle, as well as arteriovenous malformations, aneurysms, and dural arteriovenous fistulas can all exert pressure on the nerve.

After continuing to the apex of the petrous portion of the temporal bone, the nerve traverses the dura to enter Meckel’s cave, a CSF-filled cavity posterolateral to the cavernous sinus, which contains the trigeminal or gasserian ganglion. Infiltrative tumors as well as granulomatous disease can impinge on the ganglion.

The nerve then separates into three divisions (Fig. 33-1), each of which can be compressed by local inflammatory conditions or primary neoplastic or metastatic lesions. The ophthalmic nerve (V1) courses anteriorly through the cavernous sinus, where it is accompanied by cranial nerves III, IV, VI, and V.² It exits the skull through the superior orbital fissure and passes into the orbit. From there, it divides to supply the eyeball, lacrimal glands, conjunctiva, part of the nasal mucosa, and skin of the nose, eyelid, and forehead.

Figure 33-1 Anatomy of the trigeminal nerve.

Image from http://www.frca.co.uk/images/trigeminal_nerve.jpg, accessed 2010, March 14, courtesy of AnaesthesiaUK.

The maxillary nerve (V2) also passes through the cavernous sinus and then exits the skull inferolaterally through the foramen rotundum and into the pterygopalatine fossa. The nerve then continues anteriorly in the orbital floor and emerges as the infraorbital nerve, which innervates the middle third of the face and upper teeth.

The mandibular nerve (V3) exits the skull more proximally through the foramen ovale and passes into the masticator space. It supplies the lower third of the face as well as the tongue and floor of the mouth and jaw. The motor root, which bypasses the gasserian ganglion but then rejoins the mandibular nerve provides innervation to the muscles of mastication (see Fig. 33-1).

Pathophysiology

Although Jannetta and colleagues showed that surgical decompression of the nerve root can effectively alleviate the symptoms of trigeminal neuralgia, a pathophysiologic connection between trigeminal nerve compression and the intermittent nature of the disease has not been well elucidated.⁴ A disease mechanism must also explain how nonnoxious peripheral mechanical stimuli trigger pain within different regions of the face. In a number of patients who undergo surgical exploration, no compressing vessel or lesion has been identified.

Pathologic rhizotomy specimens have demonstrated focal loss of myelin with close apposition of the demyelinated axons.^5,6 Hilton found five patients without microvascular compression who did not show demyelinating features. In the study by Devor and colleagues, 1 of the 12 patients was not found to have vascular compression, and the rhizotomy specimen from this patient showed only “modest dysmyelination”.

How the demyelination—if indeed that is not an epiphenomenon—contributes to the pain is also not clear. One possibility is that the compressed and demyelinated neurons may have increased ephaptic transmission, spread from axon to axon versus along an individual axon.

Devor and his colleagues proposed their “ignition hypothesis” by which nerve compression leads to an increase in neuronal activity and reduced firing thresholds.⁶ In support of this hypothesis, Vos and colleagues showed in rats that mild compression of the infraorbital nerve produces a facial pain syndrome.⁷

There are case reports of bilateral trigeminal neuralgia. Many of these cases result from demyelinating lesions of multiple sclerosis. Other cases have occurred in patients with Charcot-Marie-Tooth disease, presumably due to an increased sensitivity to nerve compression.

Diagnosis

The White and Sweet criteria for trigeminal neuralgia⁸ were a major advance that facilitated research and enabled early and accurate clinical recognition of the syndrome (Tables 33-2 through 33-4). The criteria were incorporated, largely unchanged, into the official research diagnostic framework criteria published by the International Association for the Study of Pain (IASP)⁹ and the International Headache Society (IHS).³

Table 33-2 Sweet Diagnostic Criteria for Trigeminal Neuralgia

From White JC, Sweet WH: Pain and the Neurosurgeon. Springfield, Ill. Charles C Thomas, 1969.

Table 33-3 ICHD Criteria for Classic Trigeminal Neuralgia

ICHD, International Classification of Headache Disorders.

Table 33-4 ICHD Criteria for Symptomatic Trigeminal Neuralgia

ICHD, International Classification of Headache Disorders.

The current IHS criteria (International Classification of Headache Disorders II [ICHD-II])³ establishes trigeminal neuralgia as a discrete clinical diagnosis under the general classification of “cranial neuralgias and central causes of facial pain” (ICHD-II diagnostic code 13). The diagnosis ‘‘trigeminal neuralgia’’ (diagnostic code 13.1) replaces the earlier term, tic douloureux. ICHD-II further subdivides trigeminal neuralgia into ‘‘classic trigeminal neuralgia’’ and ‘‘symptomatic trigeminal neuralgia.’’ Classic trigeminal neuralgia (Table 33-3) is the most common idiopathic form of the disorder (although it also includes cases associated with vascular compression). Classic trigeminal neuralgia is defined as ‘‘a unilateral disorder characterized by brief electric shocklike pains, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve. Pain is commonly evoked by trivial stimuli including washing, shaving, smoking, talking and/or brushing the teeth (trigger factors) and frequently occurs spontaneously. Small areas in the nasolabial fold and/or chin may be particularly susceptible to the precipitation of pain (trigger areas). The pains usually remit for variable periods.’’ The ICHD-II specific diagnostic criteria for classic trigeminal neuralgia are listed in Table 33-3. Symptomatic trigeminal neuralgia has the same key features of trigeminal neuralgia but results from another disease process (such as multiple sclerosis or a cerebellopontine angle tumor). Symptomatic trigeminal neuralgia is defined by IHS as ‘‘Pain indistinguishable from classic trigeminal neuralgia but caused by a demonstrable structural lesion other than vascular compression.’’ The ICHD-II diagnostic criteria for symptomatic trigeminal neuralgia are listed in Table 33-4.

Because a significant percentage of patients have symptomatic trigeminal neuralgia resulting from another disease process, diagnostic brain imaging studies should be part of the initial evaluation of any patient with trigeminal neuralgia symptoms.^10,11 The study should visualize the anatomic landmarks around the trigeminal (gasserian) ganglion and the cerebellopontine angle. Although a routine brain CT scan is usually adequate to screen for a cerebellopontine tumor, an MRI scan often better demonstrates multiple sclerosis plaques and the anatomic relationships of the trigeminal root. High-resolution imaging techniques are also increasingly able to visualize subtle vascular anomalies that may be the source of root compression in certain patients with classic trigeminal neuralgia. Other diagnostic studies, such as blood studies, lumbar puncture, and evoked potentials, are generally not necessary.

Medical Treatment

Carbamazepine has been the mainstay of medical treatment for trigeminal neuralgia for many years.¹² A Cochrane review on this subject confirmed that carbamazepine with a number needed to treat (the number of people who would need to be treated to see benefit in one person) of 2.5 was the recommended initial treatment for trigeminal neuralgia.¹³ Antiepileptic drugs were first used in the treatment of trigeminal neuralgia when Bergouignan in 1942 noted that the anticonvulsant phenytoin effectively controlled attacks of pain in the condition.¹⁴ Studies on various antiepileptic drugs have revealed that although carbamazepine and lamotrigine are superior to placebo in trials, most others drugs thought to be useful do not have trials to support their use.¹⁵ Baclofen is another choice for monotherapy for trigeminal neuralgia as was evidenced in data from Fromm and colleagues.¹⁶ In many instances where carbamazepine is not tolerated, initial therapy with baclofen has been successful.

Clonazepam is a benzodiazepine with anticonvulsant properties and is also effective for suppression of pain attacks. Gabapentin, topiramate, oxcarbazepine, tiagabine, levetiracetam, and zonisamide have also been effective in treatment of trigeminal neuralgia, although the number of published clinical studies with these agents is presently small.

Therapy routinely begins with one agent, given in gradually increasing doses until pain attacks are suppressed or reduced in intensity. When a patient only partially responds to single-drug therapy at dosages that evoke side effects, rotation to another agent or adding a second drug may enhance the therapeutic response.

Although the drugs are classified as anticonvulsants, they have differing mechanisms of action as well as side effect patterns. In a retrospective study of anticonvulsant therapy, Scrivani and coworkers found that 50% of patients reported satisfactory pain relief while taking a single antiepileptic drug, whereas 70% of those taking two drugs reported a satisfactory response.¹⁷

Interventional Approaches

These can be broadly classified as peripheral techniques and those directed at the gasserian ganglion. In general, when surgical options are considered, techniques directed at the gasserian ganglion have largely replaced peripheral techniques. We will also approach neurostimulation and its role in the management of trigeminal neuralgia.

There is a paucity in the literature directly comparing medical management with surgical management. Given inconsistency in outcome measurements, poor quality of studies (most do not have independent assessment), and lack of direct comparisons, this leads to a limited ability to truly assess. Zakrzewska and associates compared the medical and surgical management of intractable trigeminal neuralgia. This is a long-term prospective longitudinal study comparing 15 patients who were followed for a mean duration of 15 years on the effectiveness of medical (oxcarbazepine) versus surgical therapy. The study indicated that mean time to recurrence of pain following oxcarbazepine therapy was 8 months and with surgical therapy it was 28 months. Clinical and patient global analysis of the outcome measures suggested that patients could benefit substantially from having surgery earlier, rather than later, in the disease process to improve the quality of life, freedom from medication, and the need for regular follow-up. Remember: this was a study group of only 15 patients.¹⁹

Block of the Ophthalmic Nerve

The ophthalmic nerve per se is not blocked in the treatment of trigeminal neuralgia because it leads to keratitis. The supraorbital and supratrochlear branches can be individually blocked. The supraorbital nerve block is described elsewhere in this text. The supratrochlear nerve can be injected at the superior medial corner of the orbital ridge with 1 mL of local anesthetic with or without corticosteroid. The inferior orbital nerve can be injected at the inferior orbital foramen which is 1 cm below the orbit and is usually located with a needle inserted about 2 cm lateral to the nasal and directed superiorly, posteriorly, and slightly laterally (Fig. 33-2).

Figure 33-2 Supraorbital, supratrochlear, infratrochlear, and infraorbital nerve blocks.

Block of the Maxillary Nerve and its Branches

With the patient’s mouth opened, a 3.5-inch, 25-gauge needle can be inserted between the zygomatic arch and the notch of the mandible. At about 3 to 4 cm in depth, contact will be made with the lateral pterygoid plate. Withdraw the needle 1 cm and angle it superiorly and anteriorly to pass into the pterygopalatine fossa. Local anesthetic (4 to 6 mL) can then be instilled here after negative aspiration. This technique anesthetizes the maxillary nerve and the sphenopalatine ganglion. There is a risk of hemorrhage when blocking the maxillary nerve with this technique (Fig 33-3).

Figure 33-3 Maxillary nerve block.

Gasserian Ganglion Techniques

Techniques targeting the gasserian ganglion can broadly be classified into ablative and decompressive approaches. Percutaneous trigeminal ablation of the gasserian ganglion is usually performed by a specially designed device inserted into the cheek or through the mouth. Under radiographic guidance with fluoroscopy or CT, the device is directed through the foramen ovale into the gasserian ganglion or retrogasserian rootlets. The methods of ablation typically include radiofrequency coagulation, glycerol injection, and mechanotrauma by balloon ablation. The results from any of these modalities depends on the duration and intensity of denervation (Fig. 33-4).

Figure 33-4 Percutaneous needle to the gasserian ganglion.

(Image from http://www.umanitoba.ca/cranial_nerves/trigeminal neuralgia/manuscript/rhizotomies.html; © 2001, The Centre for Cranial Nerve Disorders.)

Radiofrequency Thermocoagulation

Radiofrequency thermocoagulation is the most common surgical treatment for trigeminal neuralgia. A meta-analysis of the literature confirmed the efficacy of this procedure.²⁶ The recurrence rate quoted ranges from 4% to 65%.This wide variation in part was due to differing standards for defining recurrence. Some studies classified recurrence as pain severe enough to require surgery, and others as in recurrence of symptoms. The most important factors influencing recurrence are the duration of follow-up and the degree of denervation.

Taha and Tew reviewed the therapy in 500 patients that were followed for 2 to 12 years with patients who had undergone other surgical treatments for trigeminal neuralgia.²⁷ The authors found a 100% technical success rate for completion of the radiofrequency procedure, the highest rates for initial pain relief, and one of the lowest pain recurrence rates for RT (radiofrequency treatment) when compared with other surgical procedures. A recurrence rate of only 20% in 9 years was reported (Fig 33-5).

Figure 33-5 Radiofrequency lesioning of trigeminal nerve.

(Image from http://www.spinesurgeon.com.au/Neurological_Conditions/images/trigeminal_Neuralgia_clip_image009.jpg, accessed 2010, March 14.)

Glycerol Injections

Percutaneous injection of glycerol was described initially by Hakanson.²⁸ Glycerol injection involves the injection of sterile glycerol into the gasserian ganglion and retrogasserian rootlets. Placement of the needle adjacent to the ganglion is confirmed with contrast cisternogram. The procedure results in significant initial pain relief.

North, in 1990, reviewed 109 percutaneous retrogasserian glycerol rhizotomies in 85 patients, 11 with atypical features (constant pain and/or significant sensory loss unexplained by prior procedures).²⁹ They were followed for 6 to 54 months. The endpoints were recurrence requiring medication and recurrence refractory to medication requiring further intervention. Mean duration for primary endpoint was 2 years, and 3 years for secondary endpoint. Mean time to failure of repeat treatment was 1 year. There were two reported cases of corneal anesthesia and three of hyperesthesia.

As initially described, there was a low incidence of complications, dysesthesia, or keratitis, and little loss of sensation. In fact, glycerol injection replaced neurolysis by ethanol and phenol, both of which caused significant sensory loss. However, many recent larger series have shown that complications do occur frequently, and the recurrence rate is relatively high, up to 50%.^30–32

Balloon Microcompression

Balloon microcompression of the trigeminal ganglion is done with a Fogarty balloon catheter that can be inserted under fluoroscopy. This requires the use of a larger needle (14 gauge) from which a catheter is threaded through the foramen ovale. The balloon is inflated to predetermined pressure. This can cause temporary motor loss. There are also reports of bradyarrhythmias and blood pressure variation from the trigeminal cardiac reflex. Fewer studies have been done for this technique compared with radiofrequency thermocoagulation and glycerol injection.

Lichtor and colleagues reported a 10-year follow-up in a series of 100 patients. At 5 years, the recurrence rate was 20%, and at 10 years, it is estimated that 70% of patients will still be pain free.³³ One of the main advantages of this procedure is that the corneal reflex is maintained in most cases. However, dysesthesia occurs in 7% to 19% of the cases and may be related to compression time.

Skirving and coworkers in a retrospective review of balloon compression found there was prompt pain relief in 521/522 patients.³⁴ The recurrence rate was 19.2% within 5 years. There were symptomatic dysesthesias in 3.8% of patients (Fig 33-6).

Figure 33-6 Balloon decompression gasserian ganglion.

(Image from http://fns.med.upatras.gr/images/image100.jpg, accessed 2010, March 14; courtesy of Constantine Constantoyannis, MD, Functional Neurosurgery, University of Patras, Greece. © 2008.)

Stereotactic Radiosurgery

Stereotactic radiosurgery is becoming more widely practiced and is the least invasive of these procedures. A stereotactic head frame is screwed onto the skull, and stereotactic imaging is performed. The trigeminal system is irradiated. A maximum radiosurgical dose of 70 Gy or greater was associated with a greater chance of complete pain relief. Pain relief begins approximately 3 to 6 months after the procedure. Disadvantages of this technique include a roughly 20% to 30% risk of decreased sensation in the nerve after the treatment. Radiosurgery involves the application of ionizing radiation to a portion of the brain. The long-term effects of targeted radiation to the brain have not been studied.

Most patient series enrolled fewer than 100 patients with follow-up of less than 1 year. Kondziolka and associates reported 80% initial pain relief in 106 patients who were followed for 18 months.³⁵ Ten percent of the patients developed dysesthesia as a complication (Fig 33-7).

Figure 33-7 Gamma knife surgery.

(Image from http://www.umanitoba.ca/cranial_nerves/trigeminal_neuralgia/manuscript/rhizotomies.html; © 2001, The Centre for Cranial Nerve Disorders.)

Decompressive Procedures

These procedures are based on the concept that compression of the trigeminal nerve causes trigeminal neuralgia.³⁶ The compression of the trigeminal nerve from blood vessels or tumors is thought to result in demyelination of the nerve. There is evidence from clinical and anatomic studies that supports the neurovascular compression theory of trigeminal neuralgia.^37,38 However, there are many patients who do not experience pain relief following trigeminal nerve decompression, suggesting that there are etiologies other than compression of the nerve that could cause trigeminal neuralgia (Fig 33-8).

Figure 33-8 Posterior fossa with trigeminal nerve (V) shown.

(Image from http://www.mayfieldclinic.com/PE-AnatBrain.htm, accessed 2010, March 14; © Mayfield Clinic.)

Microvascular Decompression

Microvascular decompression is indicated in patients who are unable to achieve adequate relief through medical management and have an anticipated survival greater than 5 years and are considered candidates for a craniotomy under general anesthesia.

Walter Dandy was the first to put forth the posterior fossa approach for the treatment of trigeminal neuralgia.³⁹ In 1934, Dandy proposed his theory of vascular compression as a cause, but also acknowledged that vascular contact occasionally occurs without the production of pain and may be absent when neuralgia is present. Dandy identified the major compressing vessel as the anterior inferior cerebellar artery. Peter Jannetta documented the frequent occurrence of vascular channels compressing the trigeminal nerve in patients with trigeminal neuralgia and devised a technique for nondestructive microvascular decompression of the nerve.⁴⁰

Microvascular decompression involves a craniotomy to expose the nerve at the base of the brainstem and to then insert a tiny polytetrafluoroethylene (Teflon) pad between the compressing vessel and the nerve. This Teflon pad isolates the nerve from the pulsating effect and pressure of the blood vessel.

Barker and colleagues have reported an excellent long-term (20 years) prospective longitudinal study on the outcome of microvascular decompression for trigeminal neuralgia in 1185 patients. Ten years after surgery, 70% of the patients had excellent final results; they were free of pain without need for medication. Major complications included deaths (0.2%), brainstem infarction (0.1%), and ipsilateral hearing loss (1%). Initial relief of neuralgia pain was present in 98% of patients⁴¹ (Fig. 33-9).

Figure 33-9 Microvascular decompression.

(Image from http://www.health-res.com/EX/07-27-22/ph.mvdsurgery.gif, accessed 2010, March 14.)

Conclusion

Trigeminal neuralgia is estimated to affect 1 in 15,000 people. Diagnosis especially with atypical presentations can be challenging and diagnostic nerve blocks as described earlier can be helpful. Although the mainstay of therapy is still medications, neurolysis, surgical options, and neuromodulation have all been employed to treat advanced presentations.