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Home , Neuralgia, Trigeminal neuralgia

Clinical Evidence Handbook A Publication of BMJ Publishing Group

Trigeminal JOANNA M. ZAKRZEWSKA, Eastman Dental Hospital, London, United Kingdom MARK E. LINSKEY, University of California Irvine, Irvine, California

This is one in a series of is a sudden, unilateral, over time and become less responsive to chapters excerpted from brief, stabbing, recurrent in the distri- , despite dose increases and add- the Clinical Evidence Handbook, published by bution of one or more branches of the fifth ing further agents. the BMJ Publishing Group, cranial . The diagnosis is made using Treatment success is defined differently in London, U.K. The medical the history alone, based on characteristic studies of medical and surgical therapies for information contained features of the pain. trigeminal neuralgia. herein is the most accurate available at the date of • Pain occurs in paroxysms, which can • Treatment success in medical studies publication. More updated last from a few seconds to several minutes. is usually defined as at least 50% pain relief and comprehensive infor- The frequency of the paroxysms ranges from from baseline. However, complete pain relief mation on this topic may a few to hundreds of attacks per day. is the measure of treatment success in surgi- be available in future print editions of the Clinical Evi- • Periods of remission can last for months cal studies. dence Handbook, as well to years, but tend to get shorter over time. is considered the first-line as online at http://www. • The condition can impair activities of medication for the initial medical treatment clinicalevidence.bmj.com daily living and lead to . of trigeminal neuralgia symptoms. (subscription required). • The annual incidence in the United • Carbamazepine has been shown to This series is coordinated Kingdom (based on physician practice lists increase pain relief compared with placebo, by Kenny Lin, MD, MPH, Associate Deputy Editor and rather liberal diagnostic criteria) has but also increases adverse effects, such as for AFP Online. been reported to be 26.8 per 100,000. How- drowsiness, dizziness, rash, liver damage, A collection of Clinical ever, studies in other countries with stricter and ataxia. Evidence Handbook pub- definitions, such as the United States and • Studies evaluating durability of response lished in AFP is available the Netherlands, have reported much lower with carbamazepine are lacking, but consen- at http://www.aafp.org/ incidence rates ranging between 5.9 and sus expert opinion suggests that it may have afp/bmj. 12.6 per 100,000. a greater than 50% failure rate for long-term CME This clinical content Experts find that symptoms worsen (five to 10 years) pain control. conforms to AAFP criteria • for continuing medical education (CME). See CME Quiz Questions on What are the effects of ongoing treatments in persons with trigeminal page 90. neuralgia? Author disclosure: Joanna M. Zakrzewska and Mark Likely to be beneficial (in persons with who develop trigeminal E. Linskey are authors of neuralgia)* references cited in this Carbamazepine review. * Trade-off between Microvascular decompression* benefits and harms Nonpercutaneous destructive neurosurgical techniques (stereotactic radiosurgery)* Percutaneous destructive neurosurgical techniques (radiofrequency thermocoagulation, glycerol rhizolysis, or balloon compression)* Unknown effectiveness

*—Categorization based on observational studies and/or consensus.

July 15, 2016 ◆ Volume 94, Number 2 www.aafp.org/afp American Family Physician 133 Clinical Evidence Handbook

• Based on the strength of published evi- We found no RCT evidence comparing dence, carbamazepine remains the best- percutaneous destructive neurosurgical supported standard medical treatment for techniques (radiofrequency thermocoag- trigeminal neuralgia. ulation, glycerol rhizolysis, balloon com- There is consensus that oxcarbazepine is an pression) or nonpercutaneous destructive effective treatment in persons with trigemi- neurosurgical techniques (stereotactic nal neuralgia and may have fewer adverse radiosurgery) vs. placebo/no treatment or effects than carbamazepine, although there other treatments covered in this review in is a lack of data from randomized controlled persons with trigeminal neuralgia. trials (RCTs) to confirm this. • Observational data suggest that radio- • Oxcarbazepine rarely provides complete frequency thermocoagulation may offer or long-term pain relief, although studies higher rates of complete pain relief than evaluating durability of response with this glycerol rhizolysis and stereotactic radiosur- drug are lacking. gery, but may also be associated with higher We found no sufficient evidence to judge rates of complications (e.g., facial numbness, the effectiveness of baclofen or lamotrigine. corneal insensitivity). • Lamotrigine is often used in persons • In contrast with stereotactic radiosur- who cannot tolerate carbamazepine, but the gery, pain relief with microvascular decom- dose must be increased slowly to avoid rashes, pression and percutaneous destructive thus making it unsuitable for acute use. neurosurgical techniques is immediate, but • There is consensus that baclofen may they require sedation and/or to be useful for persons with multiple sclerosis perform, which are not required for stereo- who develop trigeminal neuralgia. tactic radiosurgery. We found no evidence comparing gaba- pentin vs. placebo/no treatment or other Definition treatments covered in this review in persons Trigeminal neuralgia is a characteristic pain with trigeminal neuralgia. in the distribution of one or more branches • Gabapentin does have support for use in of the fifth cranial nerve. The diagnosis is treating other conditions, made on the history alone, based on char- particularly multiple sclerosis. acteristic features of the pain. It occurs in Despite a lack of RCT data, observational paroxysms, with each lasting from a few evidence supports the use of microvascular seconds to several minutes. The frequency of decompression to relieve symptoms of tri- paroxysms is highly variable, ranging from geminal neuralgia. hundreds of attacks per day to long periods • Microvascular decompression has been of remission that can last years. Between shown in at least two prospective com- paroxysms, the person is asymptomatic. The parative cohort trials to have superiority pain is severe and described as intense, sharp, over stereotactic radiosurgery for complete superficial, stabbing, or shooting, often like pain relief, durability of response (up to an electric shock. It can be triggered by light five years), and preservation of trigeminal touch in any area innervated by the trigemi- sensation. nal nerve, including from eating, talking, • However, microvascular decompression washing the , or brushing the teeth. The requires general anesthesia and is rarely condition can impair activities of daily living associated with surgical complications, of and lead to depression. which a less than 5% risk of ipsilateral hear- In some persons, there remains a back- ing loss appears to be the most common. ground pain of lower intensity for 50% of •Well-conducted observational stud- the time. This has been termed atypical tri- ies have demonstrated that microvascular geminal neuralgia or type 2 trigeminal neu- decompression has a greater magnitude of ralgia. The International Classification for therapeutic effect than any medical and Disorders refers to this condition surgical therapy for trigeminal neuralgia. As as trigeminal neuralgia with concomitant such, this procedure is unlikely to be com- pain. Other causes of facial pain may need pared with best medical therapy in an RCT. to be excluded. In trigeminal neuralgia, the

134 American Family Physician www.aafp.org/afp Volume 94, Number 2 ◆ July 15, 2016 Clinical Evidence Handbook neurologic examination is usually normal (relative risk = 1.53; 95% confidence interval, but sensory and autonomic symptoms may 0.30 to 4.50). be reported, and persons with longer histo- ries may demonstrate subtle sensory loss on Prognosis careful examination. One retrospective cohort study found no reduction in 10-year survival in persons Incidence and Prevalence with trigeminal neuralgia. We found no evi- Most evidence about the incidence and prev- dence about the natural history of trigeminal alence of trigeminal neuralgia is from the neuralgia. However, the TNA Facial Pain United States. The annual incidence (age Association continues to periodically receive adjusted to the 1980 age distribution of the individual isolated reports of persons with United States) is 5.9 per 100,000 women and trigeminal neuralgia who either die from 3.4 per 100,000 men. The incidence tends to overdose of , take their own be slightly higher in women at all ages, and life, or both. The illness is characterized by increases with age. In men older than 80 recurrences and remissions. Many persons years, the incidence is 45.2 per 100,000. One have periods of remission with no pain last- questionnaire survey of neurologic disease in ing months or years. At least 50% of persons a French village found one out of 993 per- with trigeminal neuralgia will have remis- sons had trigeminal neuralgia. A retrospec- sions lasting at least six months. tive cohort study in UK primary care, which Collective expert experience suggests examined the histories of 6.8 million persons, that, in many persons, trigeminal neuralgia found that 8,268 persons had trigeminal neu- becomes more severe and less responsive ralgia, giving it an incidence of 26.8 per to treatment over time, despite increas- 100,000 person-years. A similar primary care ing medication doses and adding additional study carried out in the Netherlands reported agents. Most persons with trigeminal neu- an incidence of 12.6 per 100,000 person- ralgia are initially managed medically, and years when trained neurologists reviewed the some eventually have a surgical procedure. data. A population-based study in Germany We found no good evidence about the pro- reported a lifetime prevalence of 0.3%. portion of persons who require surgical treatment for pain control. Anecdotal evi- Etiology and Risk Factors dence indicates that pain relief is better The cause of trigeminal neuralgia remains after surgery than with medical treatment. unclear, but the most common hypothesis is Furthermore, responses from a question- that of the ignition theory. More peripheral naire taken by persons who had surgery and central mechanisms may be involved, for trigeminal neuralgia indicated that the and microstructure may be majority of respondents wished they had altered. It is more common in persons with surgery earlier. multiple sclerosis (relative risk = 20.0; 95% SEARCH DATE: September 2013 confidence interval, 4.1 to 59.0) and . Hypertension is a risk factor in women (rela- Adapted with permission from Zakrzewska JM, Linskey ME. Trigeminal neuralgia. Clin Evid Handbook. December tive risk = 2.1; 95% confidence interval, 1.2 2015:452-454. Visit http://www.clinicalevidence.bmj. to 3.4), but the evidence is less clear for men com for full text and references. ■

July 15, 2016 ◆ Volume 94, Number 2 www.aafp.org/afp American Family Physician 135