Trigeminal neuralgia

Author(s): Ada Lyn Yao, MD and Ashot Kotcharian, MD

Originally published:07/17/2013

Last updated:03/27/2017

1. DISEASE/DISORDER

Definition

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.

The International Association for the Study of Pain suggests three variants:

  1. Classical trigeminal neuralgia
  2. Symptomatic trigeminal neuralgia
  3. Idiopathic trigeminal neuralgia1,2,3,4

Etiology

With the three types of TN, TN may be idiopathic or caused by focal compression of the trigeminal root by tortuous or aberrant vessels in the posterior fossa1,2,3,4. Other causes are slowly growing tumors, saccular aneurysms or arteriovenous malformations compressing the trigeminal nerve root near the dorsal root entry zone1,2,3,4.

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 year5,6.

Females are 1.5 times more likely to have trigeminal neuralgia2,5,6.

The disease can appear at any age, though 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 TN2,3.

Patho-anatomy/physiology

To elaborate on the three variants of TN,

  1. 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 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 for1,3,6.
  2. 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
  3. Idiopathic trigeminal neuralgia is when no pathological finding is found4.

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

History

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).

Physical examination

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

Functional assessment

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.

Imaging

High resolution MRI helps demonstrate neurovascular compression and confirm morphologic changes of the trigeminal nerve root for classical TN.3,4

MRI readily identifies major neurologic diseases such as cerebellopontine angle tumors or multiple sclerosis plaques that may be the culprit for secondary TN.

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

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/).

Professional Issues

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

2. 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

Second-line treatment for refractory cases is based on little evidence. Other seizure medications such as baclofen, valproate, lamotrigine, anti-spasticity agents such as tizanidine, 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

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 and 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 a 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:

  1. 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
  1. Percutaneous Gasserian ganglion techniques: these are destructive interventions targeting the Gasserian ganglion itself throughradiofrequency thermocoagulation or percutaneous glycerol rhizolysis, or balloon compression.1,2,3,4
  1. 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
  1. 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 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

Gaps in the evidence-based knowledge

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.
  • Carbamezapine 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.

REFERENCES

1. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia: An international Journal of Headache. 2004;24(1):1–160.

2. Truini A, Galeotti F, Cruccu G. New insight into trigeminal neuralgia. Journal of Headache and Pain. 2005;6:237–239.

3. Cruccu G, Truini A. Trigeminal neuralgia and orofacial pains. In: Pappagallo M, ed. The Neurological Basis of Pain. New York, NY: McGraw-Hill; 2004:401–414.

4. Cruccu G, et al. Diagnosis of trigeminal neuralgia: a new appraisal based on clinical and neurophysiological findings. Brainstem Function and Dysfunction. Amsterdam, the Netherlands: Elsevier; 2006:171-186.

5. Barker FG, et al. The long-term outcome of microvascular decompression for trigeminal neuralgia. NEJM.1996;334:1077–1083.

6. Love S, Coakham HB. Trigeminal neuralgia pathology and pathogenesis. Brain. 2001;124:2347-2360.

7. Jensen TS, Rasmussen P, Reske-Nielsen E. Association of trigeminal neuralgia with multiple sclerosis: clinical and pathological features. Acta Neurologica Scandinavica. 1982;65:182–189.

8. 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.

9. Gupta, et al. Familial trigeminal neuralgia. Neurology India. 2001;50(1):87-89.

10. Krafft, R. Trigeminal Neuralgia. American Family Physician. 2008;7:9:1291-1296.

11. Katusic S, Beard CM, Bergstralh E, Kurland LT. Incidence and clinical features of trigeminal neuralgia, Rochester, Minnesota, 1945–1984. Annals of Neurology. 1990;27(1):89–95.

12. 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.

13. Burchiel KJ. Abnormal impulse generation in focally demyelinated trigeminal roots. Journal of Neurosurgery. 1980;53:674–683.

14. Dubner R, Sharav Y, Gracely RH, Price DD. Idiopathic trigeminal neuralgia: sensory features and pain mechanisms. Pain. 1987;31:23–33.

15. Tanaka, et al. Trigeminal neuralgia associated with tentorial agenesis and temporal lobe herniation: a case report. Neurol Med Chir. 2000;40(2):124-127.

16. Gronseth, et al. Practice Parameter: The diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology. 2008;71(15):1183-1190.

17. Bennetto, et al. Trigeminal neuralgia and its management. BMJ. 2007;334:201-205.

18. Nurmikko TJ, Eldridge PR. Trigeminal neuralgia pathophysiology, diagnosis and current treatment. British Journal of Anaesthesia. 2001;87:117-132.

19. Deuschl G, Eisen A. Recommendations for the practice of clinical neurophysiology: IFCN Guidelines. Electroencephalography and Clinical Neurophysiology. 1999;52:1-304.

20. Cruccu G, et al. EFNS guidelines on neuropathic pain assessment. European Journal of Neurology. 2004;11:153–162.

21. 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.

22. Nurmikko TJ. Altered cutaneous sensation in trigeminal neuralgia. Archives of Neurology. 1991;48:523–527.

23. Barker, et al. The long-term outcome of microvascular decompression for trigeminal neuralgia. NEJM. 1996;334(17):1077-1083.

24. Piovesan EJ, et al. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology. 2005;65(8):1306–1308.

25. Fromm GH, et al. Pre‐trigeminal neuralgia. Neurology. 1990;40:1493-1495.

26. Takeda, at al. Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain. Molecular Pain. 2011;7.

27. Green D, et al. Post-herpetic trigeminal neuralgia treated with deep brain stimulation. Journal of Clinical Neuroscience. 2003;10:512-514.

Original Version of the Topic 

Marykatharine Nutini, DO, Dennis Nutini, MD. Trigeminal Neuralgia. 07/17/2013.

Author Disclosure

Ada Lyn Yao, MD
Nothing to Disclose
Ashot Kotcharian, MD
Nothing to Disclose

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