Trigeminal neuralgia is a characteristic pain in the distribution of one or more branches of the fifth cranial nerve. The diagnosis is made on the history alone, based on characteristic features of the pain. It occurs in paroxysms, with each pain lasting from a few seconds to several minutes. The frequency of paroxysms is highly variable, ranging from hundreds of attacks a day to long periods of remission that can last years. Between paroxysms, the person is asymptomatic. The pain is severe and described as intense, sharp, superficial, stabbing, or shooting — often like an electric shock. It can be triggered by light touch in any area innervated by the trigeminal nerve, including eating, talking, washing the face, or cleaning the teeth. The condition can impair activities of daily living and lead to depression. In some people there remains a background pain of lower intensity for 50% of the time. This has been termed atypical trigeminal neuralgia or type 2 trigeminal neuralgia. The International Classification for Headache Disorders (ICHD) refers to this condition as trigeminal neuralgia with concomitant pain. Other causes of facial pain may need to be excluded. In trigeminal neuralgia, the neurological examination is usually normal but sensory and autonomic symptoms may be reported, and people with longer histories may demonstrate subtle sensory loss on careful examination.
Most evidence about the incidence and prevalence of trigeminal neuralgia is from the US. The annual incidence (age adjusted to the 1980 age distribution of the US) is 5.9/100,000 women and 3.4/100,000 men. The incidence tends to be slightly higher in women at all ages, and increases with age. In men aged over 80 years, the incidence is 45.2/100,000. One questionnaire survey of neurological disease in one French village found one person with trigeminal neuralgia among 993 people. A retrospective cohort study in UK primary care, which examined the histories of 6.8 million people, found that 8268 people had trigeminal neuralgia, giving it an incidence of 26.8/100,000 person-years. A similar primary care study carried out in the Netherlands reported an incidence of 12.6/100,000 person-years when trained neurologists reviewed the data. A population-based study in Germany reported a lifetime prevalence of 0.3%.
Aetiology/ Risk factors
The cause of trigeminal neuralgia remains unclear but the most common hypothesis is that of the ignition theory. More peripheral and central mechanisms may be involved, and trigeminal nerve microstructure may be altered. It is more common in people with multiple sclerosis (RR 20.0, 95% CI 4.1 to 59.0) and stroke. Hypertension is a risk factor in women (RR 2.1, 95% CI 1.2 to 3.4), but the evidence is less clear for men (RR 1.53, 95% CI 0.30 to 4.50).
One retrospective cohort study found no reduction in 10-year survival in people with trigeminal neuralgia. We found no evidence about the natural history of trigeminal neuralgia. However, the TNA Facial Pain Association continues to periodically receive individual isolated reports of people with trigeminal neuralgia who either die from overdose of medications, take their own life, or both. The illness is characterised by recurrences and remissions. Many people have periods of remission with no pain lasting months or years. At least 50% of people with trigeminal neuralgia will have remissions lasting at least 6 months in duration. Collective expert experience suggest that, in many people, trigeminal neuralgia becomes more severe and less responsive to treatment over time, despite increasing medication doses and adding additional agents. Most people with trigeminal neuralgia are initially managed medically, and a proportion eventually have a surgical procedure. We found no good evidence about the proportion of people who require surgical treatment for pain control. Anecdotal evidence indicates that pain relief is better after surgery than with medical treatment. Furthermore, responses from a questionnaire taken by people who had surgery for trigeminal neuralgia indicated that the majority of respondents wished they had surgery earlier.
Aims of intervention
To relieve pain, with minimal adverse effects.
Pain relief: pain frequency and severity scores; psychological distress; ability to perform normal activities; adverse effects.
Clinical Evidence search and appraisal September 2013. The following databases were used to identify studies for this systematic review: Medline 1966 to September 2013, Embase 1980 to September 2013, and The Cochrane Database of Systematic Reviews 2013, issue 8 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. An information specialist identified the titles and abstracts in an initial search, which an evidence scanner then assessed against predefined criteria. An evidence analyst then assessed full texts for potentially relevant studies against predefined criteria. An expert contributor was consulted on studies selected for inclusion. An evidence analyst then extracted all data relevant to the review. Study design criteria for inclusion in this review were: published systematic reviews and RCTs, at least single-blinded and containing more than 10 individuals, of whom more than 80% were followed up. There was no minimum length of follow-up. We included systematic reviews and RCTs where harms on an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are continually added to the review as required. The contributors have also used results from their own database, collated from 1990 to September 2007, which includes case series reports; further studies after this date have been added to the Comment sections. As Clinical Evidence was unable to perform a second appraisal of results retrieved by the contributor's search, we may have missed studies that could affect our overall assessment of the interventions in this review. As Clinical Evidence reports only systematic reviews and RCTs, studies from the additional searches that did not meet this criteria (e.g., case series reports) are reported in the Comment sections, and not the Benefits and Harms tables of this review. Trigeminal neuralgia is a very painful condition and, therefore, placebo-controlled trials are considered unethical. Trials using active controls have important limitations. The gold-standard drug for treating trigeminal neuralgia is carbamazepine, but it is difficult to be sure that its effects have been totally eliminated before crossover when compared with other drug treatments in trials with crossover designs. This is because carbamazepine alters liver enzymes, and reversal of this takes about 3 weeks. The choice of active control is limited because few drugs have been subjected to high-quality trials. An enhanced, enriched, randomised control trial has been suggested as a method of overcoming these obstacles. Another limitation of trigeminal neuralgia trials is that outcomes for treatment success differ for medical (drug) therapies and surgical interventions. For example, treatment success in medical studies is usually defined as at least 50% pain relief from baseline. However, complete pain relief is the measure of treatment success in surgical studies. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as RRs and ORs. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).