Trigeminal neuralgia (TN) or tic douloureux is a paroxysmal, usually unilateral disorder, characterized by brief painful episodes commonly described as intense, sharp, stabbing, shock-like pains within one or more divisions of the trigeminal nerve (ophthalmic V1, maxillary V2 and mandibular V3). The classification system and diagnostic criteria are as follows.
The International Association for the Study of Pain suggests three variants:
- Classical trigeminal neuralgia
- Symptomatic trigeminal neuralgia
- Idiopathic trigeminal neuralgia1,2,3,4
The International Classification of Headache Disorders, Third Edition (ICHD-3) suggests the diagnostic criteria for TN as below:
A) Recurrent paroxysms of unilateral facial pain in the distribution(s) of one or more divisions of the trigeminal nerve, with no radiation beyond, and fulfilling criteria B and C
B) Pain has all the following characteristics:
- Lasting from a fraction of a second to two minutes
- Severe intensity
- Electric shock-like, shooting, stabbing, or sharp in quality
C) Precipitated by innocuous stimuli within the affected trigeminal distribution
D) Not better accounted for by another ICHD-3 diagnosis
Etiologies of TN may be idiopathic or caused by focal compression of the trigeminal root by tortuous or aberrant vessels in the posterior fossa.1,2,3,4 Other causes are slowly growing tumors, saccular aneurysms or arteriovenous malformations compressing the trigeminal nerve root near the dorsal root entry zone.1,2,3,4
Epidemiology including risk factors and primary prevention
TN is a rare disease. Epidemiological studies showed that approximately 4 to 28.9/100,000 persons worldwide experience TN.1,4,5,6
In the United States, there are approximately 15,000 new cases each year.5,6 Classic TN accounts for 80% of cases, secondary TN 15% and idiopathic TN 5-10%.30,31
Females are 1.5 times more likely to have trigeminal neuralgia.2,5,6
The disease can appear at any age, however it is rare in children and it occurs after age 40 in more than 90% of cases, with peak age between 52-58 years for the classical type and 30-35 years for the symptomatic form of TN.2,3
Familial cases, though rare, have also been reported.28,29
Preliminary data for risk factors has hypothesized that hypertension and migraines may be risk factors for developing TN.32,33,34
No methods for primary prevention have been proposed.
To elaborate on the three variants of TN
- Classical trigeminal neuralgia is the most common variant and occurs often with no apparent cause although this may be explained by compression of the trigeminal nerve root close to the brainstem (dorsal root entry zone) by a tortuous blood vessel (artery or vein). Compression can lead to mechanically twisted nerve fibers, can cause secondary focal demyelination, which may also be mediated by microvascular ischemic changes. These changes lower the excitatory threshold of affected fibers and promotes ephaptic cross-talk between adjacent nerve fibers. Tactile stimulus from fast-myelinated (A-beta) fibers can directly activate slow nociceptive (A-delta fibers), resulting in the high frequency discharges that TN is known for.1,3,6
- Symptomatic or secondary trigeminal neuralgia (STN) is caused by a structural lesion other than vascular compression such as from tumors (either benign or malignant), multiple sclerosis, or arteriovenous malformations.1,3,4
- Idiopathic trigeminal neuralgia is when no pathological finding is found.4
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time):
There is no evidence showing increase in frequency of the paroxysmal attacks of TN or duration of the attacks with the disease duration. Additionally, unlike other forms of neuropathic pain, TN can enter periods of complete remission in up to 63% of patients. These periods may last from weeks to years.4 Early prediction of outcomes is difficult because there is significant variability in recurrence. Significant predictors of recurrence include female sex, symptoms lasting more than eight years, venous compression of the trigeminal-root entry zone, and the lack of immediate postoperative cessation of tic, which is described as involuntary wincing due to intense pain.2,13
Specific secondary or associated conditions and complications
TN pain often provokes muscle spasm on the affected side, known as tic douloureux.1,2,3,4 Lacrimation and rhinorrhea are rare. While approximately 2.4% of MS patients develop TN, patients with other demyelinating disorders such as Charcot-Marie-Tooth develop TN rarely.1,2,3
Essentials of Assessment
The diagnosis of TN can be made usually by history alone. It should be distinguished from other causes of facial pain.1
TN is typically unilateral but a few patients develop bilateral symptoms which occur most commonly in individuals diagnosed with multiple sclerosis.
The pain strictly follows the distribution of the trigeminal nerve branches and does not extend to the posterior third of the scalp, posterior portion of the external ear, or the angle of the mandible.
Stimulus-evoked pain is a striking feature of TN; triggers and trigger zones are non-noxious mechanical stimuli within the trigeminal territory over the face, lips, gums, including the oral cavity. Such stimuli include light touch, a whiff of air, shaving, application of makeup, brushing, eating, drinking, usual movements such as smiling, talking. This pain paroxysm resembles allodynia in other conditions of neuropathic pain but unlike allodynia, TN has limited trigger zones and characteristic brisk facial muscle contractions (tics).
The physical examination is typically normal in TN which is a more useful finding exclude other diagnoses. A thorough neurological examination as well as head and neck examination should be performed, given the association of MS and tumors with TN. The ears, mouth, teeth, and temporomandibular joint should be evaluated for other causes of facial pain.9 Atypical features of the disease such as abnormal neurologic examination, ataxia, sensory abnormalities in the trigeminal area, abnormal trigeminal reflexes (corneal reflex, blink reflex, masseter inhibitory periods, jaw-jerk), focal weakness, abnormal oral, dental or ear examination, hearing abnormality or visual changes suggest secondary trigeminal neuralgia or an alternative diagnosis.5,9,15 The finding of typical trigger areas, which are most frequently perioral, is pathognomonic for TN.9
Using a multidisciplinary approach, the patient should be evaluated to determine how debilitated or limited he/she is by TN pain. Different therapeutic approaches may be used to establish baseline function and to educate the patient about pain management, such as Graded Exposure Therapy. The functional assessment may be determined using the Functional Independence Measure or other functional scales, depending on the rehabilitation team’s preference.
High resolution MRI with thin cuts through the trigeminal ganglion and heavy T2 weighting helps demonstrate neurovascular compression and confirm morphologic changes of the trigeminal nerve root for classical TN. Of note, 3D time-of-flight MRA is the most optimal study for visualizing arteries and neurovascular contact. 3,4,37
MRI readily identifies major neurologic diseases such as cerebellopontine angle tumors or multiple sclerosis plaques that may be the culprit for secondary TN.
A meta-analysis from 2014 further delineated imaging features on MRI that could diagnose symptomatic TN. Contact with the trigeminal root alone had a sensitivity of 66% and specificity of 90% diagnosis of TN, whereas when nerve atrophy co-existed, sensitivity was 52%, but specificity was increased to 100%.35
Supplemental assessment tools
Other exams such as neurophysiologic recording of trigeminal reflexes and trigeminal evoked potentials are options for patients who cannot undergo MRI.
Neurophysiological recording of trigeminal reflexes can differentiate classical TN from secondary TN. The trigeminal reflexes consist of the R1 and R2 components of the blink reflex after electrical stimulation of the ophthalmic division, SP1 and SP2 components of the masseter inhibitory reflex after electrical stimulation of the maxillary or mandibular division, and the jaw jerk to chin taps.8,11 These reflexes assess function of the trigeminal afferents from all trigeminal territories as well as the trigeminal central circuits in the brainstem.7 Typically, all reflexes are normal in classical TN but the short-latency oligosynaptic reflexes may be abnormal in secondary TN.7,8,9,11 Sensory changes in TN are usually not clinically significant and may be detected only with quantitative somatosensory testing comparisons with the unaffected side.12
Early predictions of outcomes
Early prediction of outcomes is difficult, because there is significant variability in recurrence. Significant predictors of recurrence include female sex, symptoms lasting more than eight years, venous compression of the trigeminal-root entry zone, and the lack of immediate postoperative cessation of tic.13
Environmental factors that could incite TN symptoms should be assessed.
Social role and social support system
Patients should be questioned as to how they are coping with chronic pain. Inquiries should be made into whether they would be receptive to support groups or psychological services. Patients can be directed to resources, such as the TNA Facial Pain Association website (http://www.fpa-support.org/).
Changes in location, severity, or quality of pain should alert the physician to the possibility of an alternative diagnosis (9). Nutritional consultation may be necessary, as the pain of TN may limit oral intake.16
Rehabilitation Management and Treatments
Available or current treatment guidelines
Treatment of TN is based on the use of antiepileptic drugs. First line therapy should be carbamazepine (200-1200mg/day) or oxcarbazepine (600-1800mg/day). There have been multiple Class I and II studies that established carbamazepine as effective, less so for oxcarbazepine but patients may tolerate the latter better.2,3 An additional consideration exists for patients with Asian ancestry who carry the HLA-B*15:02 gene which indicates a genetic susceptibility to developing Steven-Johnson syndrome and/or toxic epidermal necrolysis with use of carbamazepine, thus should be avoided in these patients.36
Second-line treatment for refractory cases is based on little evidence. Other seizure medications such as valproate, lamotrigine, gabapentin, pimozide, anti-spasticity agents such as tizanidine, baclofen, botulinum toxin A and topical capsaicin have been tried. Typically, lamotrigine can be added on (400mg/day) or patient may be transitioned to lamotrigine or baclofen (80mg/day max).2, 3, 38,39
For analgesia while oral medications are titrated, intravenous infusion of lidocaine (5 mg/kg administered over one hour), phenytoin (15 mg/kg administered over 30-120 minutes), fosphenytoin or subcutaneous sumatriptan (3mg injection subcutaneous followed by one week of 50mg daily oral for one week) may be used, though the evidence for this is low-grade. 40,41,42,43
Topical ophthalmic anesthesia has been found to be ineffective for controlling pain in patients with classic TN, hence should not be prescribed.3
In terms of managing secondary TN, not enough evidence has been found to support or to refute the effectiveness of any medication to treat it. There have been no placebo-controlled studies for this type of TN and existing ones are small, open label trials of MS-associated TN using lamotrigine, gabapentin, topiramate or misoprostol.2
At different disease stages
There are no distinct disease stages in TN. Occasionally episodes of TN may present without the typical characteristics but will respond well to carbamezapine. This is known as pre-TN, a dull, continuous, aching pain most often in the jaw which later develops the hallmark signs.17
Coordination of care
An interdisciplinary team approach is strongly recommended, with initial pharmacologic management by physiatrist or pain specialist. Connecting patients to resources is important. Consultations with a neuropsychologist and an occupational therapist may prove helpful.
Complementary and alternative medicine (CAM), such as acupuncture, relaxation techniques and meditation, can be considered as adjunct or alternative to pharmacotherapy.
Consultation with nutritionist is indicated if poor oral intake stems from severe pain.14
Referral to neurosurgery is indicated for cases refractory to medical management.2,4
Patient & family education
Referral to support group services should be offered. They should be educated about uncertainty of prognosis.
Measurement of Treatment Outcomes including those that are impairment-based, activity participation-based and environmentally-based
A multidisciplinary team approach that includes physical and occupational therapy and neuropsychology is indicated. This approach should incorporate consistent use of Cognitive Behavioral Therapy, Graded Exposure Therapy, desensitization techniques. Patient functional changes can be measured with Functional Independent Measurement scores or other functional grading measures.
Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills
Some experts recommend expedited referral for surgery or an interventional procedure. This should be done in a timely manner so as not to result in marked deterioration in activities of daily living.
Such interventions include:
- Peripheral techniques like cryotherapy, neurotomies, alcohol injection, phenol injection, peripheral acupuncture, radiofrequency ablation, thermocoagulation: these target portions of the trigeminal nerve distal to the Gasserian ganglion.1,2,3,4
- Percutaneous Gasserian ganglion techniques: these are destructive interventions targeting the Gasserian ganglion itself through radiofrequency thermocoagulation or percutaneous glycerol rhizolysis, or balloon compression.1,2,3,4
- Gamma knife radiosurgery uses a beam of radiation to target the trigeminal root. It remains an option for patients who cannot undergo open surgery or who have blood coagulation problems (e.g., patients who are taking warfarin).1,2,3,4
- Posterior fossa microvascular decompression of the nerve/ vessel contact or destruction of the Gasserian ganglion provides most sustain pain relief.3
Peripheral nerve stimulation has recently been gaining ground and growing evidence as a treatment option for chronic pain syndromes unresponsive to other interventions. It entails a subcutaneous insertion of one or several electrodes in the painful area and subsequent electrical stimulation.15,16
Cutting Edge/ Emerging and Unique Concepts and Practice
Cutting edge concepts and practice
Voltage gated potassium channel openers are being examined as potential therapeutic agents for TN pain.26 There is also some preliminary data that the development of selective sodium channel blockers for the Nav1.7 sodium receptor may prove more beneficial than carbamazepine or oxcarbmazepine.30More randomized controlled studies on botulinum toxin in the treatment of TN are needed to prove efficacy, though preliminary reports are promising.39
Research conducted on Schwann cell activation has identified two signaling pathways including NGF-trkA and BDNF-trkB as key in promoting myelin repair mechanisms after trigeminal nerve injury and can be further targeted in the future to develop novel methods of treating TN.44
There are reports of deep brain stimulation, electric stimulation of structures deep in the brain by an implanted pacemaker, successfully treating post-herpetic TN.27 Additionally, use of peripheral nerve stimulation is gaining favor in some pain and neurosurgical circles.
Gaps in the Evidence-Based Knowledge
While the clinical presentation of TN is well characterized, more research can be done to establish a link between other comorbid pathologies such as hypertension and migraines.32,33,34
Novel approaches to treatment including development of sodium channel blockers of the Nav 1.7 sodium receptor, botulinum toxin and research into signaling pathways of the trigeminal nerve should also be explored to develop more targeted therapies for TN.
In summary, TN is a clinical diagnosis that, as the name states, has symptoms confined within the trigeminal area.
Neurologic exam is typically normal and if not, secondary causes of TN or other causes of a patient’s signs and symptom should be considered.
- Classical TN is unusual under the age of 40 years.
- Carbamazepine is the drug of choice for initial treatment.
- Microvascular decompression is the gold standard surgical technique for classical TN.
- The finding of typical trigger areas, which are most frequently perioral, is pathognomonic for TN.
- A multidisciplinary approach, which includes the patient, physiatrist, PT, OT, neuropsychologist, and other specialties such as neurology or neurosurgery would be the most appropriate for patients with TN.
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- Chmielewska B, Keszek KM. Progression of preexisting trigeminalgia to Tolose-Hunt-like syndrome. The importance of neuroimaging for early diagnosis. Neurological Sciences. 2003;24:281–285.
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- Neto HS, Camilli JA, Marques MJ. Trigeminal neuralgia is caused by maxillary and mandibular nerve entrapment: greater incidence of right-sided facial symptoms is due to the foramen rotundum and foramen ovale being narrower on the right side of the cranium. Medical Hypotheses. 2005;65(6):1179–1182.
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- Kimura J, Rodnitzky RL, Van Allen WM. Electrodiagnostic study of trigeminal nerve: orbicularis oculi reflex and masseter reflex in trigeminal neuralgia, paratrigeminal syndrome, and other lesions of the trigeminal nerve. Neurology. 1970;20:574–583.
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- Takeda, at al. Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain. Molecular Pain. 2011;7.
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Original Version of the Topic
Marykatharine Nutini, DO, Dennis Nutini, MD. Trigeminal Neuralgia. 7/17/2013.
Previous Revision(s) of the Topic
Ada Lyn Yao, MD, Ashot Kotcharian, MD. Trigeminal Neuralgia. 3/27/2017.
Kirk Lercher, MD
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Prathusha Maduri, DO
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