AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Trigeminal neuralgia (TN) is a common and potentially disabling pain syndrome, the precise pathophysiology of which remains obscure. Although neurologic examination findings are normal in patients with the idiopathic variety, the clinical history is distinctive. The initial response to carbamazepine therapy typically is diagnostic and successful. Despite obtaining this satisfying early relief with medication, patients may experience breakthrough pain that requires additional drugs and, in some patients, one or more of a variety of surgical interventions.

Historical note

In 1900, in a landmark article, Cushing reported a method of total ablation of the gasserian ganglion to treat TN.

In 1912 Osler described TN as follows:

• In patients with advanced TN, the paroxysms follow one another rapidly without any assignable cause, and in the intervals the patient may never be quite free from pain.
• They are initiated by almost any form of external stimulus, for example by a draught of air; movement of the facial muscles or tongue while speaking; touching the skin, particularly over those points from which the pain seems to take its origin; and the act of swallowing, especially when the pain involves the mucous membrane field of distribution of the nerve.
• It is not a self-limited disease. In some instances, the neuralgia reaches such a frightful intensity that it renders the patient's life unbearable. In earlier times, suicide was not an uncommon consequence.

Pathophysiology

Usually no structural lesion is present, although many investigators agree that vascular compression, typically venous or arterial loops at the trigeminal nerve entry into the pons, is critical to the pathogenesis of the idiopathic variety. This compression results in focal trigeminal nerve demyelination.

Since the exact pathophysiology remains controversial, TN may have either a central and/or peripheral etiology.

Frequency

United States

According to Penman in 1968, the prevalence of TN is approximately 107 men and 200 women per 1 million people. Mauskop states that approximately 40,000 patients in the US suffer from this condition at any particular time. The incidence is 4-5 cases per 100,000.

Rushton and Olafson found that approximately 1% of patients with multiple sclerosis (MS) develop TN, whereas Jensen et al stated that 2% of patients with TN have MS.

Mortality/Morbidity

• TN is not associated with a shortened life. However, the morbidity associated with the chronic and recurrent facial pain can be considerable if the condition is not controlled adequately.
• Individuals may choose to limit activities that precipitate pain, such as chewing, possibly losing weight in extreme circumstances.
• TN may evolve into a chronic pain syndrome, and patients may suffer from depression and related loss of daily functioning.

Race

No racial risk factors have been identified.

Sex

The male-to-female ratio is 2:3.

Age

• Age of onset typically is 60-70 years; thus, advanced age is a major risk factor.
• Patients who present with the disease when aged 20-40 years are more likely to suffer from a demyelinating lesion in the pons secondary to MS.
• MS and hypertension are the 2 risk factors found in epidemiologic studies.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Clinical presentation
• • TN presents as a stabbing unilateral facial pain that is triggered by chewing or similar activities or by touching affected areas on the face.
  • Patients can localize their pain precisely. The pain is not confined exclusively to one of the 3 divisions of the nerve but more commonly runs along the line dividing either the mandibular and maxillary nerves or the mandibular and ophthalmic portions of the nerve.
    • Of patients, 60% complain of lancinating pain shooting from the corner of the mouth to the angle of the jaw.
    • Jolts of pain from the upper lip or canine teeth to the eye and eyebrow, sparing the orbit itself, are experienced by 30% of patients. This distribution falls between the division of the first and second portions of the nerve.
    • According to Patten, less than 5% of patients experience ophthalmic branch involvement.
  • Strictly unilateral, the disorder affects the right side of the face 5 times more frequently than the left.
  • Pain quality is characteristically severe, paroxysmal, and lancinating.
    • It commences with a sensation of electrical shocks in an affected area, then quickly crescendos in less than 20 seconds to an excruciating discomfort felt deep in the face, often contorting the patient's expression.
    • The pain then begins to fade within seconds, only to give way to a burning ache lasting seconds to minutes.
  • During attacks, patients may grimace; hence the term "tic douloureux."
  • The number of attacks may vary from less than one per day, to a dozen or more per hour, up to hundreds per day. Outbursts fully abate between attacks, even when they are severe and frequent.
  • TN is an exception to the rule that nerve injuries typically produce symptoms of constant pain and allodynia. If the pain is particularly frequent, patients may be difficult to examine during the height of an attack.
  • A valuable clue to the diagnosis is the triggering of the pain with certain activities. Patients carefully avoid rubbing the face or shaving a trigger area, in contrast to other facial pain syndromes, in which they massage the face or apply heat or ice.
    • According to Sands, trigger zones, or areas of increased sensitivity, are present in one half of patients and often lie near the nose or mouth.
    • Chewing, talking, smiling, or drinking cold or hot fluids may initiate TN pain. Touching, shaving, brushing teeth, blowing the nose, or encountering cold air from an open automobile window also may elicit pain.
  • In contrast to migrainous pain, persons with TN rarely suffer attacks during sleep, which is a key point in the history.
  • Patients with MS and TN have similar complaints to those with the idiopathic variety, except that they present at a much younger age (often <40 y).
    • Some present with atypical facial pain, without trigger zones, and without the lancinating brief paroxysms of discomfort.
    • As previously noted, TN is not unusual in MS, but it is rarely the first manifestation. Typically, it occurs in the advanced stages of MS.
• Natural history and prognosis
• • After an initial attack, the disorder may remit for months or even years. Thereafter the attacks may become more frequent, more easily triggered, more disabling, and may require long-term medication.
  • Patients may find immediate and satisfying relief with one medication, typically carbamazepine. However, over the years, they may require a second or third drug to control breakthrough episodes and finally may need surgical intervention.
  • Simpler, less invasive procedures are well tolerated but usually provide only short-term relief.
    • At this point, further and perhaps more invasive operations may be required, and with these procedures the risk of the disabling adverse effect of anesthesia dolorosa increases.
    • The long-term prognosis of this disorder varies.
  • According to Fromm et al, some patients may present with pretrigeminal neuralgia syndrome for a period of weeks or even years before developing the customary symptoms of TN. They complain of an unrelenting sinus pain or toothache lasting for hours, triggered by moving the jaw or drinking fluids. Not surprisingly, they first seek dental care. Some find benefit from baclofen or carbamazepine.

Physical

• In idiopathic TN, neurologic examination findings are normal.
• • Facial sensation, masseter bulk and strength, and corneal reflexes should be intact.
  • No sensory loss is found unless checked immediately after a burst of pain. Any permanent area of numbness excludes the diagnosis.
  • The corneal reflex also should be intact. Loss of this reflex also excludes the diagnosis of idiopathic TN, unless a previous trigeminal nerve section procedure has been performed.
  • The diagnosis of idiopathic TN is tenable only if no physical findings of fifth nerve dysfunction are present.
  • Any jaw or facial weakness or swallowing difficulties suggests another etiology.
  • In patients with MS or a structural lesion and TN, sensory loss often is found on examination.
• Any objective abnormalities in the neurologic examination exclude the diagnosis of idiopathic TN.

Causes

Other diagnostic considerations are relevant with TN.

• Other syndromes with paroxysmal lancinating head pain include the less common glossopharyngeal neuralgia (GN) and occipital neuralgia (ON) syndromes.
• • GN causes pain in the tonsillar fossa, posterior pharynx, and ear and may be initiated by coughing, yawning, or swallowing cold liquids.
    • During acute attacks of this disease, which frequently is associated with an underlying pathology, the patient may be unable to speak and tries to avoid moving the lips or tongue.

    • An involuntary startle during an attempt to touch the affected side of the face is diagnostic.
  • ON causes pain in the posterior head region.
    • Thus, the distribution easily distinguishes it from TN.

    • Confusion arises only if the patient cannot provide a clear history.

• According to Goadsby and Lipton, paroxysmal hemicrania syndromes typically last only seconds, similar to TN, but occur in and around one eye.
• • Intense unilateral conjunctival injection and lacrimation signal an autonomic component, which further distinguishes this condition.
  • This condition does not respond to carbamazepine.

• Migraine and cluster headaches may produce severe unilateral pain but are not triggered by movement or contact with the face; nor do they respond promptly to carbamazepine.
• According to Turp and Gobetti, atypical face pain usually extends beyond the distribution of the fifth cranial nerve, rarely is triggered, and presents with a steady unrelenting discomfort lasting hours to days.
• Secondary TN is a consideration.
• • When pain is associated with hyperesthesia along the course of the fifth nerve or is observed with other cranial neuropathies, symptomatic or secondary TN is much more likely than the idiopathic form.
  • Further investigation may reveal MS, a tumor in the posterior fossa, or a tumor on the trigeminal nerve.
  • Acoustic neuromas, cerebral aneurysms, trigeminal neuromas, and meningiomas can produce syndromes similar to idiopathic TN. Consider these conditions in patients with onset of pain when younger than 40 years, those with predominant forehead and/or orbit pain (ie, first division of the trigeminal nerve), or those with bilateral facial pain.
  • Further, consider secondary TN in patients with bilateral sensory loss or weakness of the facial muscles or jaw.
  • Patients with prominent hemifacial spasm, especially if it is continuous, may have tic convulsif, a condition associated with a dilated and ectatic basilar artery or other vascular malformation compressing the trigeminal nerve.
  • Brain MRI with and without contrast is critical in diagnosing the secondary causes of TN.

• Trigeminal neuropathy also is a consideration.
• • As noted, idiopathic TN presents as episodic, unilateral, lancinating, triggerable, often shocklike facial pain with pain-free intervals.
  • Trigeminal neuropathic pain, by contrast, presents as a constant, unilateral, often mild facial pain with prominent sensory loss. It is nontriggerable and unremitting. It may be either symptomatic or idiopathic.
  • To further complicate diagnostic matters, the clinician may encounter atypical TN, a syndrome that overlaps TN and trigeminal neuropathy.
    • This syndrome consists of constant pain that episodically intensifies.

    • According to Burcheil, these patients experience both lancinating triggered pain and a baseline, constant, dull and throbbing discomfort.

    • The atypical form may occur in up to 5% of people after facial surgery or significant trauma and in 1-5% after the removal of impacted teeth.

    • In the experience of many neurosurgeons, atypical trigeminal neuralgic pain results from lesions or injuries of the trigeminal nerve root distal to the route entry zone but with even greater compression than found in the idiopathic form of TN.

• In contrast to trigeminal neuropathy, whether typical or atypical, atypical facial pain is distinguished by the extension of discomfort beyond the distribution of the fifth cranial nerve and by the frequent lack of triggers.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Glossopharyngeal neuralgia
Occipital neuralgia
Tic convulsif
Trigeminal neuropathy
Acoustic neuroma
Brainstem syndromes
Chronic pain programs
Granulomatous angiitis
Malignant and non-malignant pain syndromes
Ramsay-Hunt syndrome
Sarcoidosis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No laboratory, electrophysiologic, or radiologic testing routinely is indicated for diagnosis.

Imaging Studies

• Brain MRI with and without contrast helps to distinguish secondary causes of TN from the idiopathic form. The study is indicated in patients presenting with the condition when younger than 60 years, principally to exclude tumor.
• In patients older than 60 years, the clinician may first choose to assess the response to a therapeutic trial of medication before considering imaging. A clear relief of pain with carbamazepine or another anticonvulsant confirms the diagnosis of idiopathic TN.
• Rarely, MS presents with TN. Consider MS in the diagnostic evaluation of individuals who display other features of this demyelinating disorder.

Other Tests

• No other diagnostic testing is indicated.

Procedures

• No further procedures are indicated for the diagnosis of this disorder.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Since most patients incur TN when older than 60 years, medical management is the logical initial therapy. Medical therapy often is sufficient and effective, allowing surgical consideration only if pharmacologic treatment fails.
• Because this disorder may remit spontaneously after 6-12 months, patients may elect to discontinue their medication in the first year following the diagnosis. Most must restart medication in the future.
• Serum levels of carbamazepine (but not necessarily phenytoin) in ranges appropriate for epilepsy may be necessary, at least to control initial symptoms, although a much smaller maintenance dosage may be adequate thereafter.
• According to Dalessio, medications work by interrupting the temporal summation of afferent impulses that precipitate the attack.
• Once a patient experiences breakthrough pain on a single agent, a second and even third additional medication may be required to restore relief.
• Carbamazepine is the drug of choice for TN. A 100-mg tablet may produce significant and complete relief within 2 hours, and for this reason it is a suitable agent for initial trial.
  • So predictable and powerful is the relief that if the patient does not respond at least partially to carbamazepine, reconsider the diagnosis of idiopathic TN.
  • If this dosage does not relieve the discomfort adequately, administer a higher dose.

• Gabapentin has demonstrated effectiveness.

• In 1997, Sist et al reported 2 patients with TN responsive to gabapentin. One previously was unresponsive to carbamazepine.
• In 1998, Khan reported complete relief of secondary TN in 6 of 7 patients with MS receiving gabapentin doses from 900-2400 mg/d.
  • The patients previously had not responded to a variety of drugs.
  • Once on gabapentin, 2 subjects were able to discontinue all other pain medications, and the remaining 5 could stop all but one other pain medication.
  • All patients maintained the response at 1 year of therapy with minimal adverse effects.
• In a similar, uncontrolled, small study of patients with MS, Solaro et al reported that 5 of 6 individuals found complete and sustained relief with gabapentin.

• Lamotrigine, another new antiseizure medication, was reported by Lunardi et al to provide impressive and sustained relief of TN in one small, open-label, prospective study.

• All 5 patients with symptomatic TN associated with MS and 11 of 15 patients with idiopathic disease gained complete relief.
• This was maintained during a follow-up period of 3-8 months.
• Drug levels closely predicted pain relief, although the dosage required for adequate relief varied widely from 100-400 mg/d.

• To date, the efficacy of gabapentin and lamotrigine versus placebo or their efficacy in patients whose pain is refractory to carbamazepine has not been established. As stated by Carrazana and Schachter, of these 2 new agents, gabapentin has advantages, which include faster titration, no known drug interactions, and no known idiosyncratic skin reaction.
• Phenytoin, although not approved by the FDA for idiopathic TN and believed to be less effective than carbamazepine, probably is effective for some patients with this disorder according to Loesser.

• It has the same mechanism of action as carbamazepine and poses a similar risk panel, except for the risk of aplastic anemia. Of those who fail to attain relief with carbamazepine alone, an additional 8-20% of patients may respond adequately if phenytoin is added to the treatment regimen.
• According to one small study by Braham, phenytoin produced complete relief of pain in 30-40% of 43 patients and partial relief in an additional 30-40% at 300-600 mg/d.
• Blom stated that doses of 300 mg/d were less effective, although doses of 400-600 mg caused more adverse effects.
• No correlation has been found between blood levels of phenytoin and therapeutic effect. Loesser recommends that the dose can be increased until relief is obtained or undesirable adverse effects appear (eg, dizziness, ataxia, diplopia, nystagmus, nausea).
• Raskin reports relief of intolerable pain with 250 mg of intravenous phenytoin over 5 minutes, allowing relief for hours to 3 days, sufficient for an adequate history and re-examination.

• Other anticonvulsant agents possibly useful in the treatment of this disorder include sodium valproate and clonazepam. According to Zakrzewska et al, their therapeutic efficacy has not been confirmed by formal studies.
• The National Institute of Health (NIH) currently is sponsoring studies of topiramate.
• Baclofen may be effective in patients with TN.

• Commonly, baclofen is added to anticonvulsants when breakthrough symptoms occur.
• In 1980, Fromm et al demonstrated baclofen to be useful in a small, uncontrolled study. Of the 14 patients with idiopathic TN resistant to carbamazepine, 10 found relief with 60-80 mg/d of baclofen.
• The starting dosage is 10 mg/d, which can be increased, if needed, to 60-80 mg/d administered 3-4 times per day (it has a short half-life of 3-4 h).
• According to Parkeh et al and Raskin, the dose of carbamazepine then may be reduced to 500 mg/d to maintain a putative synergistic effect.
• A novel purified version, L-baclofen, currently is under investigation at the University of Pittsburgh. L-baclofen may prove more effective in TN.

• The NIH also is investigating the use of dextromethorphan in doses much higher than those used in over-the-counter cough preparations.
• Tricyclic antidepressants (eg, amitriptyline, nortriptyline) have not been studied formally.

Surgical Care

Over time, the drugs used for the treatment of TN often lose effectiveness as patients experience breakthrough pain. For patients in whom medical therapy has failed, surgery is a viable and effective option. According to Dalessio, 25-50% of patients eventually stop responding to drug therapy and require some form of alternative treatment. The clinician then may consider referral to a surgeon for one of the procedures discussed below. Among patients who develop TN when younger than 60 years, surgery is the definitive treatment.

Neurosurgery is generally most helpful in those patients with paroxysmal rather than constant pain, and pain following the anatomic distribution of one or more trigeminal distributions, rather than spread diffusely. The various operations often fail after 1 or several years of initial relief. This requires a repeat procedure, often with improved but still incomplete results. Thus, many patients eventually restart pain medication after surgery.

Surgery appears to be less effective for TN secondary to MS.

Surgery exposes the patient to operative risks and the risk of permanent, residual facial numbness and dysesthesias. The primary complications of surgery include permanent anesthesia over the face or the troubling dysesthetic syndrome of anesthesia dolorosa—often disabling, occasionally is worse than the original TN, and often is untreatable.

Many operations have been offered to patients in recent decades. Local ablation of the peripheral nerve and wide sectioning of the sensory roots largely have been abandoned. Three operative strategies now prevail: percutaneous procedures, gamma knife surgery (GSK), and microvascular decompression (MVD). Ninety percent of patients are pain-free immediately or soon after any of the operations, although the relief is much more long-lasting with MVD. Pain-free intervals after percutaneous procedures (PRGR and PBM) last 1.5-2 years, 3-4 years after another (PRTG), and 15 years commonly after MVD (Sweet, 1988). Percutaneous surgeries make sense for older patients with medically unresponsive TN. Younger patients and those expected to do well under general anesthesia should first consider microvascular decompression–presently the most cost-effective surgery.

The cost per quality adjusted pain-free year was $6,342, $8,174, and $8,269 for glycerol rhizotomy, microvascular decompression, and stereotactic radiosurgery, respectively, according to Pollack. Approximately 8000 patients with TN undergo surgery each year in the United States, at an estimated cost exceeding $100 million, as of 2005.

Many patients require pain medication even after surgery.

The primary complications of surgery include permanent anesthesia over the face or the troubling dysesthetic syndrome of anesthesia dolorosa. Anesthesia dolorosa can be disabling, occasionally is worse than the original TN, and often is untreatable. For this reason, procedures with the best long-term success and the least risk of a residual facial dysesthetic syndrome are the most promising.

• Percutaneous surgeries
• • Percutaneous procedures usually can be performed on an outpatient basis under local or brief general anesthesia at acceptable or minimal risk of morbidity. For these reasons, they commonly are performed in debilitated persons or those older than 65 years. Zakrzweska and Thomas described 3 types of procedures: percutaneous radiofrequency trigeminal gangliolysis (PRTG), percutaneous retrogasserian glycerol rhizotomy (PRGR), and percutaneous balloon microcompression (PBM). Patients are left with minor, local, residual facial numbness after PRTG; may occasionally lose sensation after PRGR; and rarely do so after PBM. In each procedure, the surgeon introduces a trocar or needle lateral to the corner of the mouth and, under fluoroscopic guidance, into the ipsilateral foramen ovale. The ganglion is lysed at this location.
  • In PRTG, a radiofrequency heating tip sears the ganglion until the area of facial pain becomes numb. In PRGR, a spinal needle likewise penetrates the face, this time to the trigeminal cistern, at which point a cisternogram is obtained with water-soluble contrast material. After removing this material, the surgeon instills anhydrous glycerol, asking the patient to remain seated for an additional 2 hours to fully ablate the nerve.
  • With PBM, the operator inserts a balloon catheter through the foramen ovale into the region of the ganglion and inflates it for 1-10 minutes. PRTG has gained wide acceptance according to several investigators, because the patient is awake during the procedure, recovers quickly, and goes home the day of the procedure or the next day. According to Tan et al, the recurrence rate approaches 25% with PRTG, and occasionally patients suffer complications of jaw weakness and corneal anesthesia.
  • As related by Meglio and Cioni, some surgeons report excellent results with PBM, which are comparable to those with PRTG. PRGR may be the favored procedure, as it includes only a minimal risk of disturbed facial sensitivity postoperatively. However, Cappiabianca et al and Taha and Tew, who favor the radiofrequency rhizotomy, argue that PRGR has the highest rate of pain recurrence.
• Gamma knife surgery
  • Gamma knife surgery (GKS) has become more widely available since 2000. It appears about as effective as the percutaneous procedures but takes weeks to months to bring relief and costs slightly more.
  • Kondziolka and Lunsford report that progress with this technique has been slow but has accelerated as surgeons have learned to target the nerve precisely with stereotactic MRI, have determined the proper radiation dose to quickly relieve pain without incurring facial sensory loss, and have ascertained the length of the nerve to be radiated.
  • In Kondziolka et al's study of 106 subjects, most patients already had no relief with either microvascular decompression or glycerol rhizotomy. At a median follow-up point of 18 months, 60% of patients were pain free, 17% were moderately improved, and 23% were minimally or not improved.
  • Kondziolka concludes that this technique is minimally invasive, is associated with a low risk (10%) of facial paresthesias or sensory loss, and offers a high rate (86%) of significant, initial pain relief.
  • The pain recurrence rate is low for patients who initially attain complete relief. It is generally effective, even in patients in whom prior surgery or medication trials failed. Patients must wait 1 month for the pain to resolve.
  • Stereotactic GSK is less technically demanding, less operator-dependent, and less invasive than the percutaneous procedures.
  • In 1953, Leskell irradiated the trigeminal nerve in 2 patients with good initial success but did not publish this data until 1971. Progress really began when, in the 1990s, surgeons learned to target the nerve precisely with stereotactic MRI, determine the proper radiation dose to quickly relieve pain without incurring facial sensory loss, and ascertain the length of nerve to be radiated.
• • Henson compared GSK to PRGR in 188 patients and concluded that GSK improved pain more consistently and induced less residual facial paresthesia. Pollack reviewed a group of 121 individuals who underwent one or the other procedure and found the rates of complete pain relief similar, about 60% at 6 months and 54% at 24 months. Sheehan reported in a study of 151 patients that 47% were pain-free after 1 year and 34% after 3 years. Nine percent suffered incurred new facial numbness after the procedure. In a similar but smaller study (N=49) of patients followed for a mean of 49 months, one third of whom had also failed either MVD or PRGR, GKS provided complete relief, even off medications, in 14 patients (32%) and partial but durable relief in 27 patients (61%) (McNatt). Others report rather disparate complete pain relief, from 42% (Jawahar) to 59 % (Drzymala) to 60% (Pollack) to 80% (Urgosik).
  • In these prospective but open and uncontrolled trials, complete pain relief predictably waned substantially by year 3-5, as with the percutaneous procedures.
  • Pain relief also arrives much more slowly, often coming only 3-12 weeks after the procedure, too long a wait perhaps for some individuals.
  • New facial numbness or paresthesias develop slowly over the first 12-15 months after GSK, reaching bothersome levels in 9-20% of patients.
• Microvascular decompression
• • Microvascular decompression commonly is performed in younger, healthier patients, especially those with pain isolated to the ophthalmic division or in all 3 divisions of the trigeminal nerve and in those with secondary TN.
  • Surgeons perform the operation under general anesthesia, incising the skin behind the ear and performing a 3-cm craniectomy. After retracting the dura to expose the trigeminal nerve, they identify an arterial loop compressing the nerve as it enters the pons. They then pad the vascular structure with Teflon felt.
  • Patients spend 4-10 days in the hospital and another week convalescing at home. Thus, recovery is more prolonged than with percutaneous procedures.
  • Mortality for this more invasive procedure approaches 0.5%. Serious morbidity includes dizziness, cerebrospinal fluid leaks, meningitis, cerebellar stroke, and hearing loss, which may occur in 1-5% of cases.
• Effectiveness of surgical procedures in TN has been studied.
• • Burcheil reports that 90% of patients are pain free after any of the operations mentioned above. Those in whom the first percutaneous procedure fails may undergo a repeat procedure, which usually provides relief.
  • Sweet reports that pain-free intervals after PRGR and PBM procedures last 1.5-2 years, and they last 3-4 years after PRTG. For the microvascular decompression procedure, 15 years of relief is typical.

Consultations

• Neurosurgical consultation is needed when medical treatment does not effectively control episodes of breakthrough facial pain.

Diet

No dietary guidelines are known to improve the outcome in TN.

Activity

• Patients learn quickly to avoid activities that trigger episodes of trigeminal pain, such as rubbing the face. Men may choose to grow beards to avoid regular shaving.
• A patient information guide is available at Trigeminal Neuralgia Association, PO Box 340, Barnegat Light, NJ 08006. Phone: 609-361-0982; Fax: 609-361-0982.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Please see Medical Care section.

For most patients, those incurring TN after age 60 years, medical management is the logical initial therapy. Medical therapy often is sufficient and effective, allowing surgical consideration only if pharmacologic treatment fails. The overlap between the underlying pathophysiologic mechanisms of some epilepsy models and neuropathic pain models supports their use in neuropathic pain in general and in TN specifically. Their exact mechanisms of action remain unclear.

Antiepileptic drugs (AEDs) work well and have been known to do so since a study was completed with phenytoin (PHE) in 1942 (Bergouignan) and another with carbamazepine (CBZ) in 1962 (Blom, 1962). With 3 placebo-controlled crossover studies validating its efficacy in TN, providing relief by roughly 75% versus only 25% in the placebo arms (Killian, Nicol, Campbell), CBZ is the best studied drug for this disorder and the only one with FDA approval in the setting. Since the CBZ studies, however, newer second- and third-generation AEDs have expanded the choice of AED in TN, having demonstrated their efficacy in a variety of neuropathic pain syndromes, including TN, as well as in painful diabetic polyneuropathy and postherpetic neuralgia.

Because patients with TN will be using medications for years, perhaps decades, their cost is relevant. Generic CBZ is the cheapest; costs vary widely for the other agents, depending on the source, but approach a 4-fold increase for generic gabapentin (GBP), 8-fold for lamotrigine (LTG), 10-fold for topiramate (TPM), and 20-fold for oxcarbazepine (OCB) in moderate daily doses. To justify these hugely higher costs, providers can point to the promise of improved tolerability of the new agents, often a determining factor in a person with multiple sclerosis or with advanced age. Some drugs do not affect serious idiosyncratic hepatic and hematopoietic reactions, eliminating the burden and cost of routine laboratory monitoring. Some offer more linear pharmacokinetics and fewer drug-drug interactions, facilitating combination therapy. Some pose less long-term risk for osteoporosis. Further, some do not autoinduce their metabolism, simplifying dose titration and adjustment.

Most of the literature on medications for TN consists of case series, uncontrolled studies with less than a dozen subjects, or small randomized clinical trials, so the apparent efficacy of the drugs requires confirmation through well-designed, large, phase III trials. The controlled data published for LTG and BCF is promising but derives from studies with only 14 and 10 subjects, respectively. No controlled data exist for the use of phenytoin, clonazepam, sodium valproate, oxcarbazepine, gabapentin, or mexiletine in TN; similarly, no controlled data exist for the common practice of adding a second drug when the first fails, except for the addition of LTG to CBZ. No head-to-head comparison studies of these agents exists, and only one surgery versus medication study has been published, limited to refractory TN, a small (N=15) trial. Only one Cochran review of medications for TN exists, and it looks only at CBZ, the traditional favorite. Confusion arises over outcome measures, as researchers accept only

complete relief of pain while others accept partial relief.

Serum levels of the anticonvulsants in ranges appropriate for epilepsy may be necessary, at least to control initial symptoms; a much smaller maintenance dosage may be adequate thereafter. Because this disorder may remit spontaneously after 6-12 months, patients may elect to discontinue medication, only to restart it when the pain recurs. Once a patient experiences breakthrough pain on a single agent, a second and even third additional medication may be required to restore relief, at which point, many seek a surgical solution. Resistance develops anywhere from 2 months to 10 years after treatment begins with the most studied and successful drug, CBZ.

Botulinum toxin was shown to be successful for at least 90 days in a single case report (Allam, 2005) in a patient in whom CBZ and rhizolysis had previously failed. Dextromethorphan failed in 2 patients with TN in a randomized, double-blind, crossover trial of patients with various facial neuralgias (Gilron, 2000). Tricyclic antidepressants (eg, amitriptyline, nortriptyline), as well as sodium valproate or pregabalin, have not been well studied. Anecdotal reports exist for success with clonazepam. Trials of newer N-methyl-D-aspartate receptor blockers have not been done. An NSAID, misoprostol, has shown modest efficacy in a small prospective open study in patients with MS (DMKG study group, 2003).

Drug Category: Anticonvulsants

Reduce excitability of gasserian ganglion neurons, preventing anomalous discharges and related lancinating volleys of pain.

Drug Category: Antispasmodic agents

Several small, uncontrolled studies in the 1970s and 1980s, including those by Parekh et al and Fromm et al, demonstrated effectiveness of baclofen, particularly when added to an existing regimen of carbamazepine that is not providing adequate pain control. Once baclofen is added to an anticonvulsant, the dosage of the anticonvulsant often can be reduced.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• TN is treated on an outpatient basis unless neurosurgical intervention is required.

Further Outpatient Care

• Patients who experience breakthrough pain may need an increase in the dosage of their medication, if tolerated, or the addition of a second anticonvulsant medication or baclofen. No published data from randomized, prospective, controlled studies are available to guide clinicians regarding multidrug therapy, leaving providers to empiric trials of one agent or another.
• Neurologists caring for younger patients ( <60 y at onset) should consider early neurosurgical consultation, even after a negative MRI of the brain. Surgical procedures occasionally can afford complete relief, delaying the need for anticonvulsant medications for many years, if not permanently.

In/Out Patient Meds

• Outpatient medications customarily used are reviewed in the Medication section.

Deterrence/Prevention

• No known methods of deterrence exist.

Complications

• The chief complication is the adverse effects and toxicity experienced routinely with long-term use of anticonvulsants.
• Another complication is the waning efficacy over several years of these anticonvulsants in controlling neuralgia, necessitating the addition of a second anticonvulsant, which may cause more drug-related adverse reactions.
• As noted in the Surgical Care section, both the percutaneous neurosurgical procedures and the microvascular decompression procedures pose risks of long-term complications. Perioperative risks also exist.
• Patients may have to wait for weeks or months after the operation for relief. Some find relief only for 1-2 years and then must weigh the option of a second operation.
• Many may need to continue long-term anticonvulsant therapy, although perhaps at lower dosages.
• Some patients permanently lose sensation over a portion of the face or mouth. Occasionally, patients may suffer jaw weakness and/or corneal anesthesia.
• The worst complication is anesthesia dolorosa, an intractable facial dysesthesia, which may be more disabling than the original TN.

Prognosis

• After an initial attack, the disorder may remit for months or even years. Thereafter the attacks may become more frequent, more easily triggered, disabling, and may require long-term medication.

Patient Education

• Patients benefit from an explanation of the natural history of the disorder, including the possibility that the syndrome may remit spontaneously for months or even years before they need to consider long-term anticonvulsants. For this reason, some may elect to taper off their medication after the initial attack subsides.
• Patients should avoid maneuvers that trigger pain. Once the diagnosis is established, advise them that dental extractions do not afford relief, even if pain radiates into the gums.
• Some may wish to contact the Trigeminal Neuralgia Association (Phone: 609-361-0982).
• For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education articles Trigeminal Neuralgia (Facial Nerve Pain), Tic Douloureux, and Pain Medications.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to properly assess for secondary TN is a major potential pitfall. A careful examination of the cranial nerves and an MRI of the brain, especially in an individual who develops the disorder when younger than 60 years, should protect against missing structural lesions (eg, tumor, cerebral aneurysm, acoustic neuroma).
• Anticonvulsant medications pose risks of sedation and ataxia, particularly in elderly patients, which may make driving or operating machinery hazardous. They also may pose risks to the liver and the hematologic system. Thus, documentation of patient education about these potential risks is important.
• Patients also need to understand that medications for TN are only palliative and often are of limited and temporary value. They also must be informed thoroughly of the risks involved with neurosurgical interventions, including anesthesia dolorosa.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Jun 8, 2006