Etiology and Pathogenesis

Tic douloureux can be caused by any of a number of conditions affecting the ipsilateral trigeminal system. In the vast majority, the cause seems to be compression of the trigeminal nerve at its exit from the pons by an adjacent artery or vein that has elongated and kinked to become wedged against the nerve. In about 1% to 2% of cases, the pain results from a benign tumor in the cerebellopontine angle, such as a meningioma, epidermoid tumor, or acoustic neuroma, or even an arteriovenous malformation.⁸ Other authors have indicated that 1% to 8% of patients with trigeminal neuralgia have multiple sclerosis.^9–13 Very infrequently, trigeminal neuralgia may be the presenting symptom of multiple sclerosis.¹⁴ A variety of other rare etiological associations have been reported, but all of these together probably do not account for more than a low percentage of cases. In a significant number of patients, the cause of the tic douloureux is not apparent.

The pathogenesis of trigeminal neuralgia remains uncertain, as are the mechanisms by which treatments are effective. For example, some authors have postulated that nerve root demyelination resulting from neural compression by a blood vessel or tumor or resulting from multiple sclerosis is an important feature, perhaps permitting ephaptic transmission or ectopic impulse generation between adjacent denuded axons. Both peripheral and central mechanisms are most likely required for the production of tic douloureux. Calvin and colleagues presented a comprehensive theory that utilizes two known physiological mechanisms: the trigeminal dorsal root reflex and repetitive firing of extra action potentials from a focal region of altered axonal size or myelination.¹⁵ Altered central connectivity and neuronal hyperactivity caused by deafferentation (centralist concept) as well as changes in the trigeminal myelin and axons can lead to altered peripheral sensitivity to chemical and mechanical stimuli (peripheralist concept).^15,16 However, as attractive as such ideas are, no theory has yet been postulated that explains all aspects of tic douloureux, such as the pain-free periods, which may last for months or years early in the course of the condition, the triggering of tic pain by non-noxious stimuli, the separation of the trigger areas from the painful region, and the response to anticonvulsants. Elimination of root compression by adjacent vessels does not take into account the effectiveness of numerous other surgical procedures, most of which injure the root or ganglion, but decompression of the root may relieve pain by facilitating remyelination.

Clinical Features

Tic douloureux is diagnosed almost exclusively on the basis of the patient’s history (Box 48.1). The International Headache Society defined trigeminal neuralgia as a “sudden, usually unilateral, severe, brief, stabbing, and recurrent pain in the distribution of one or more branches of the fifth cranial nerve.”^17,18 The three divisions of the trigeminal nerve are the ophthalmic, maxillary, and mandibular. For the accurate diagnosis of facial pain, a detailed knowledge of the anatomy of the fifth cranial nerve is essential. By definition, the pain of tic douloureux is confined to the distribution of one trigeminal nerve (Fig. 48.1) and more commonly affects the lower part of the face than the upper.¹⁶ The maxillary division of the fifth cranial nerve (V2) is the site of pain alone or in combination with other divisions, most commonly the mandibular division (V3) in 45% of cases. The ophthalmic division (Vl) is least likely to be affected in trigeminal neuralgia (Fig. 48.2). A small number of patients have similar pain syndromes in the territories of the nervus intermedius, glossopharyngeal nerve, or vagus nerve. The pain of untreated tic douloureux occurs unpredictably and is sudden in onset, severe in degree, and short in duration. Often the patient can experience many paroxysms of pain within a single hour, and such bouts may go on for days, with some fluctuation in frequency from hour to hour and day to day. Early in the course of the syndrome, pain-free periods lasting months are common, but as time goes on these natural remissions tend to become less frequent and less prolonged. Although tic pain is ordinarily spontaneous in onset, it can frequently be triggered by a non-noxious stimulus, such as touching the skin on that side of the face, chewing, swallowing, or talking. Some patients are sensitive in certain areas of the face, called trigger zones, which when touched cause an attack of pain. Even a gentle breeze can trigger pain in some patients. The pain has been described as lancinating, lightning-like, or electrical in quality, and has been likened to the pain experienced when a dentist drills into the pulp of a tooth.⁷ The patient may wince in response to the pain, hence the name tic douloureux. A history of bilateral tic pain can be elicited in 3% of patients, although no patient has bilateral tic pain during one episode.¹⁶

FIGURE 48.1 The peripheral and central aspects of the trigeminal nerve and its branches.

FIGURE 48.2 Distribution of pain among divisions of the trigeminal nerve in patients with tic douloureux

(Data from Loeser J. Tic douloureux. Pain Res Manage 2001;6:156-165.)

Often the patient who develops tic douloureux sees the dentist first, because lancinating lower facial pain seems to be arising from a certain tooth or teeth. Dentists are often fixated on peripheral lesions as the cause for pain. A diseased tooth in the upper jaw can cause headache on the same side, which may radiate into the orbit or face. A diseased tooth in the lower jaw may cause considerable pain in the distribution of the mandibular division of the nerve, including pain deep in the ear. In addition, dental pain is much more common than tic douloureux. Teeth may be extracted or other dental procedures performed without providing any relief of the pain of tic douloureux. The patient may also consult more than one physician before the correct diagnosis is made. In the majority of patients, the trigeminal neuralgia is idiopathic in that there is no identifiable cause.⁸ However, the presence of sensory loss mandates a thorough search for structural pathology. Patients with idiopathic trigeminal neuralgia can develop more atypical features with time in the absence of efficacious therapy. In all likelihood, this development coincides with ongoing neuropathic injury. Pain that is continuous, lacks a shock-like quality, or is associated with objective evidence of cranial nerve dysfunction should raise the suspicion of diseases other than idiopathic trigeminal neuralgia. However, the most likely cause of this type of pain is a prior ablative procedure that damages the trigeminal nerve. Atypical facial pain is described as deep, burning, and continual. There is no jabbing onset as occurs in tic douloureux. The pain can radiate behind the ear, down onto the neck, or across to the opposite maxillary area. These patients, in contrast, often clutch their face, unlike the patient with tic douloureux who shields her face but is very careful not to actually touch it (Table 48.1). Myofascial pains involving the muscles of mastication and temporomandibular joint pain occur predominantly in the lateral face. They are also described as aching, burning, or cramping pains, and are often associated with tenderness to palpation of the involved muscles.¹⁶

Deviations from the typical picture of tic douloureux can occur, although the more unusual features the patient manifests, the less likely is a favorable response to either medical or surgical therapies. Furthermore, surgical procedures that damage the trigeminal nerve can produce changes in the findings and in the patient’s symptoms. Nerve damage can lead to a burning component of the pain, although these iatrogenically acquired changes in the pain syndrome do not alter the original diagnosis. It is therefore essential to ascertain what the symptoms were prior to any intervention.

Diagnosis

The diagnosis of tic douloureux is based almost exclusively on the history; as this disease consists only of pain, no diagnostic imaging or physiological studies currently available will substitute for the history. The neurological examination is ordinarily normal except for mild sensory changes in a minority of patients in the region of their pain, with the exception that those few patients with multiple sclerosis or a large structural lesion such as a tumor in the cerebellopontine angle usually have altered trigeminal sensation and other evidence that heralds the underlying disorder. Traditionally, diagnostic radiological studies such as computed tomography or magnetic resonance imaging have been normal in the usual patient with tic douloureux, but they have been performed to identify the exceptional patient with a recognizable etiological condition such as those just mentioned.⁷ Patients with a Chiari malformation may also develop trigeminal neuralgia, thought to be the result of venous or arterial compression of the cranial nerves along with the tonsillar ectopia. Recent advances in magnetic resonance imaging and magnetic resonance angiography have improved the sensitivity and specificity of diagnosing neurovascular compression of the nerve by evaluating the anatomical relationships of the arterial and venous structures with the trigeminal nerve at the root entry zone in the cerebellopontine angle.¹⁶ However, so far these studies have been more used as a preoperative adjunct than for diagnostic purposes.^19,20 Continued development of MRI is likely to lead to the ability to discern if there is a vascular impingement on the nerve and thereby may influence choice of treatment.

Treatment

Despite the relative lack of understanding of pathophysiological mechanisms of trigeminal neuralgia, very effective medical and surgical treatments have been developed. Although generally effective treatments are available for tic douloureux, none is successful in all cases. Few or no randomized trials exist comparing medical, surgical, and interventional techniques, and therefore, treatment decisions for these patients with neuropathic pain can be challenging and are largely empiric. Furthermore, the individual patient frequently requires more than one form of treatment during the course of the disease. The psychosocial and behavioral response patterns of patients with chronic facial pain are similar to those of other patients with chronic pain.

In those few patients with an abnormality along the path of the trigeminal nerve that can be detected radiologically, such as a neoplasm in the cerebellopontine angle, the treatment is directed against the lesion that has been demonstrated. This approach ordinarily will also relieve the tic douloureux. However, the overwhelming majority of patients does not fall into this category and their symptoms must be treated in spite of the absence of structural pathology other than an adjacent blood vessel.

Surgical Treatment

Medical management should always precede a surgical procedure and no surgical procedure is warranted unless pharmacological therapy has failed either because of inadequate pain relief or unacceptable side effects. The three primary surgical treatments are gangliolysis, stereotactic radiosurgery, and suboccipital craniectomy with microvascular decompression (Box 48.2).

BOX 48.2 Surgical Management Options for Trigeminal Neuralgia

Radiofrequency gangliolysis

Balloon gangliolysis

Glycerol gangliolysis

Gamma Knife radiosurgery

Microvascular decompression

Trigeminal rhizotomy

Trigeminal tractotomy

Gasserian Gangliolysis

Trigeminal gangliolysis avoids the risks of a craniotomy and its objective is to destroy selectively the A-δ and C fibers (nociceptive) while preserving the A-α and β fibers (touch). It can be repeated easily if the pain recurs, and is associated with minimal rate of morbidity. In the gangliolysis procedure, the gasserian ganglion and adjacent sensory root of the trigeminal nerve are injured, with the expectation that a more permanent effect can be achieved than following a neurectomy because neural regeneration is less likely to occur in these areas than in the peripheral trigeminal branches. In the past, an anterior trigeminal rhizotomy was performed by exposing and dividing or otherwise injuring part or all of the main trigeminal sensory root adjacent to the gasserian ganglion.^4,5 The radiofrequency gangliolysis procedure is performed by inserting a needle through the cheek into the third division of the trigeminal nerve at the foramen ovale, and then advancing the needle under fluoroscopic guidance into the gasserian ganglion and sensory root (Fig. 48.3).^3,22,24–26 The entry point is 2.5 cm lateral to the corner of the mouth in the occlusal plane and the needle is aimed toward the intersection of the coronal plane halfway between the external auditory meatus and the lateral canthus and the sagittal plane centered at the pupil. The needle is advanced through the foramen ovale at the petrosphenoid junction and positioned at the level appropriate for the affected trigeminal branch. The third, second, and first divisions can then be stimulated in sequence by slowly advancing the needle tip. Generally, the mandibular division of the root is encountered 1 cm after penetration of the foramen ovale, V2 is located at 2 cm, and V1 is at 3 cm and at the level of the clivus. Once the needle is ideally situated, the patient is awakened and the relevant nerve root is stimulated to confirm stimulus-provoked cutaneous paresthesia in the painful trigeminal division. Contractions of the masseter and pterygoid muscles can occur at a low stimulation threshold with a medial trajectory. The patient is then reanesthetized and the neural destruction is produced by using a radiofrequency current to create a thermal lesion. Gangliolysis can also be performed under general anesthesia using a Fogarty catheter balloon to damage the ganglion mechanically, or by injecting glycerol into the cistern of the trigeminal ganglion. The goal is to produce the least neurological deficit that will control the patient’s pain.

FIGURE 48.3 Percutaneous trigeminal/gasserian rhizolysis. Lateral fluoroscopic skull image shows the needle is inserted through the cheek into the third division of the trigeminal nerve at the foramen ovale and is advanced into the gasserian ganglion and sensory root. The fibers of V3, then V2, and finally V1 are encountered in sequence as the needle is advanced toward the clivus.

Gangliolysis by any method produces pain relief for a longer period than by the injection or avulsion of a peripheral branch. Radiofrequency gangliolysis offers an 80% chance of 1-year pain relief and a 50% chance of 5-year success.^16,27 Approximately 5% to 10% will not obtain relief initially or will have an early recurrence of pain; during the 5 years after the procedure, about 25% will experience recurrence.^28,29 The complication rate of radiofrequency gangliolysis is 0.5% to 1% and can include meningitis, damage to other cranial nerves, corneal anesthesia, masseter weakness, and anesthesia dolorosa (total sensory loss). Anesthesia dolorosa is the most dreaded complication of ablative lesions of the trigeminal nerve and refers to pain in an anesthetic region. Unfortunately, no pharmacological or ablative surgical treatment is effective for this complication.²²

Balloon compression is performed under general anesthesia. Using fluoroscopic control, a large 14-gauge guide needle is inserted until it just penetrates the foramen ovale and the balloon is slowly inflated. Balloon compression is technically easier than radiofrequency thermocoagulation; it produces similar results and does not require patient participation. However, bradycardia should be anticipated during the procedure. For this reason, glycopyrrolate should be administered prior to insertion of the needle when performing any type of gangliolysis. Some authors believe that the risk of corneal hypoesthesia and anesthesia dolorosa is lower with balloon compression and therefore is the procedure of choice in patients with ophthalmic division involvement or in patients who are not good awake surgical candidates for radiofrequency gangliolysis.

Glycerol gangliolysis is less often performed today than the radiofrequency or balloon gangliolysis. Because the location of the glycerol cannot be precisely targeted after injection, the results are somewhat unpredictable; however, overall there is a lower incidence of sensory loss and anesthesia dolorosa than with the radiofrequency lesion. With glycerol gasserian rhizolysis, the long-term results are not quite as good: there is a 5% to 15% incidence of early failure and about a 20% to 30% incidence of later failure.^27,29

In general, patients are relieved for a longer period after gangliolysis than they are by the injection of alcohol into or avulsion of a peripheral branch. Therefore, peripheral neurectomy is indicated only when gangliolysis has failed and the patient cannot or will not tolerate a suboccipital microvascular decompression. Alternatively, a local anesthetic block into the trigger area or region of pain may provide transient relief until definitive therapy can be undertaken.^2,16,22

Microvascular Decompression

Vascular compression of the trigeminal nerve at its entrance into the pons is the common etiological factor in trigeminal neuralgia. Jannetta developed an operation to move the offending vessel(s) away from the nerve.^30,31 This procedure is referred to as microvascular decompression because it involves an operating microscope and microsurgical technique. The area is exposed through a lateral posterior fossa craniectomy (retromastoid craniectomy), and after the vessel or vessels are separated from the nerve, a material such as a synthetic sponge or Teflon felt is inserted to maintain the separation (Fig. 48.4). The trigeminal nerve must be carefully and circumferentially inspected along its entire intracranial course from the root entry zone to its entrance laterally into Meckel’s cave. This procedure ordinarily provides pain relief without any facial sensory loss and has a greater potential for producing long-lasting pain relief. It is interesting to note that the tic pain does not always stop immediately following a microvascular decompression, but instead may take several days. Furthermore, nerve manipulation without moving the artery will transiently stop the tic pain although it will soon recur thereafter.

FIGURE 48.4 Retromastoid craniectomy with microvascular decompression of the trigeminal nerve.

Review of the literature suggests that definite neurovascular compression is found in 88.6% of cases, but an average of 7.5% of explorations reveal no pathology intraoperatively.¹⁹ The results of microvascular decompression are excellent if arterial compression is identified. The superior cerebellar artery is the most common (70-80%) cause of trigeminal neuralgia. When the pain is perceived in V2 or V3 divisions, the usual finding intraoperatively is compression of the rostral and anterior portion of the nerve. The anterior inferior cerebellar artery is the compressive vessel in 10% of cases and occurs in the caudal and posterior portion of the nerve closest to nerve VI. Veins impact the nerve in 5% to 13% of cases.²⁵ Among 68 personal patients followed for an average of 54 months, 72% had excellent pain relief and 6% had good relief that did not lead to any sensory loss.²¹ The initial failure rate for microvascular decompression is in the 5% to 10% range.^23,28,29,32 Subsequently, the rate of pain recurrence averages about 3.5% per year. This procedure is contraindicated in patients with atypical facial pain because of the poor results achieved. Magnetic resonance angiographic imaging effectively excludes secondary causes of trigeminal neuralgia, which warrant nonmicrovascular decompression management. If no significant vascular compression is identified at operation, the main sensory root of the trigeminal nerve can be partially divided adjacent to the pons (posterior trigeminal rhizotomy). This has a similar probability of providing pain relief, but will cause some degree of facial hypoesthesia. The intrinsic somatotopic organization of the nerve tends to spare the superiorly located ophthalmic segment when performing a partial sensory rhizotomy of the lateral two thirds of the nerve.

When compared with other surgical treatments, it is widely accepted that microvascular decompression is associated with the lowest rates of recurrence and sensory loss, although more serious risks of morbidity (5%) and mortality (0.5%) are encountered than after Gamma Knife radiosurgery or gangliolysis. It has the best long-term success rate of any of the available surgical treatments. In the event of a recurrence after microvascular decompression, reexploration of the nerve can be performed, with less rewarding results, but pathological vessel impingement may not be found and a partial rhizotomy still needs to be considered.³³

Stereotaxic Radiosurgery

Gamma Knife radiosurgery has been advocated as a minimally invasive alternative surgical approach to microvascular decompression or percutaneous surgeries. The short-term results are as good as gangliolysis for tic douloureux, although as is true for all other types of treatments for this disorder, atypical clinical features or a history of prior tic surgery lowers the success rate. Currently there are two types of radiosurgery technologies: linear accelerators (linacs) and Gamma Knife. A 2009 report indicates that over 2800 patients had been treated with the Gamma Knife throughout the world by 1999. From 70% to 80% of patients are pain-free in the short-term, although up to 50% relapse. Doses of 60 to 90 Gy were used in a single session and most of the patients responded to radiosurgery within 6 months of the procedure, with a median of 2 months and a low incidence of complications.^34–38 These results are promising, although the recurrence rate and long-term morbidity rate remain to be seen. In another recent study of 102 patients, despite an 81% early response rate, 56% of patients who experienced initial pain relief suffered treatment failure. Side effects also include facial dysesthesias, corneal irritation, vascular damage, hearing loss, and facial weakness, varying with dose plan and target areas. Oddly, pain relief usually does not occur for 2 to 12 weeks after radiosurgery.^37,38

Peripheral Neurectomy

Resection or avulsion of a branch of the trigeminal nerve has a long history in the treatment of tic douloureux, but it is rarely a procedure of choice today in countries with developed health care. It produces complete anesthesia in the distribution if the avulsed branch, which can be a significant disability for the patient.³⁹ Pain relief rarely lasts more than a year or so, and repeating the procedure does not produce as good results as the original. However, if gangliolysis is not available or has failed in a patient who has also failed stereotactic radiosurgery, it could be considered.

Trigeminal Tractotomy

When all other measures have failed, sectioning of the descending trigeminal tract in the medulla produces loss of pain and temperature sensation in the ipsilateral face and pharynx but spares touch. It is carried out through a small suboccipital craniectomy and C1 and C2 laminectomy and requires both anatomical and physiological localization techniques. It is not commonly performed today, although a percutaneous method has also been described.

Conclusion

A patient with trigeminal neuralgia who has no discernible mass along the trigeminal pathways should first receive a trial of appropriate pharmacological therapy. Medical management is successful in about one half of patients. If this fails, one of the surgical approaches should then be considered, with the selection based on the location of the pain, the patient’s age and health, and the experience and preference of the surgeon. For example, for an elderly patient or one with multiple medical comorbid conditions with medically refractory trigeminal neuralgia Gamma Knife or gangliolysis should be offered as primary surgical procedures. Secondary ablative procedures, such as avulsion of peripheral branches of the trigeminal nerve or trigeminal rhizotomy or trigeminal tractotomy, need to be considered when the three primary procedures have failed.

The patient with trigeminal neuralgia may need different forms of treatment during his or her lifetime. The physician should be aware of the options, selecting the one most likely to help at that particular time, with the least risk.

Acknowledgment

This chapter contains material from the first edition of this text, and we are grateful to the author of that chapter for his contribution.