> Table of Contents > Trigeminal Neuralgia
Trigeminal Neuralgia
Noah M. Rosenberg, MD
image BASICS
DESCRIPTION
  • Disorder of the sensory nucleus of the trigeminal nerve (cranial nerve [CN] V) that produces episodic, paroxysmal, severe, lancinating facial pain lasting seconds to minutes in the distribution of >1 divisions of the nerve
  • Often precipitated by stimulation of well-defined, ipsilateral trigger zones: usually perioral, perinasal, and, occasionally, intraoral (e.g., by washing, shaving)
  • System(s) affected: nervous
  • Synonym(s): tic douloureux; Fothergill neuralgia; trifacial neuralgia; prosopalgia
EPIDEMIOLOGY
Incidence
  • Women: 5.9/100,000/year
  • Men: 3.4/100,000/year
  • >70 years of age: ˜ 25.6/100,000/year
  • Predominant age:
    • >50 years; incidence increases with age
    • Rare: <35 years of age (consider another primary disease; see “Etiology”)
  • Predominant sex: female > male (˜2:1)
Prevalence
16/100,000
Pediatric Considerations
Unusual during childhood
Pregnancy Considerations
Teratogenicity limits therapy for 1st and 2nd trimesters.
ETIOLOGY AND PATHOPHYSIOLOGY
  • Demyelination around the compression site seems to be the mechanism by which compression of nerves leads to symptoms.
  • Demyelinated lesions may set up an ectopic impulse generation causing erratic responses: hyperexcitability of damaged nerves and transmission of action potentials along adjacent, undamaged, unstimulated sensory fibers
  • Compression of trigeminal nerve by anomalous arteries or veins of posterior fossa, compressing trigeminal root
  • Etiologic classification:
    • Idiopathic (classic)
    • Secondary: cerebellopontine angle tumors (e.g., meningioma); tumors of CN V (e.g., neuroma, vascular malformations), trauma, demyelinating disease (e.g., multiple sclerosis [MS])
RISK FACTORS
Unknown
COMMONLY ASSOCIATED CONDITIONS
  • Sjögren syndrome; rheumatoid arthritis
  • Chronic meningitis
  • Acute polyneuropathy
  • MS
  • Hemifacial spasm
  • Charcot-Marie-Tooth neuropathy
  • Glossopharyngeal neuralgia
image DIAGNOSIS
PHYSICAL EXAM
All exam findings typically are negative due to the paroxysmal nature of the disorder.
DIFFERENTIAL DIAGNOSIS
  • Other forms of neuralgia usually have sensory loss. Presence of sensory loss nearly excludes the diagnosis of TN (if younger patient, frequently MS).
  • Neoplasia in cerebellopontine angle
  • Vascular malformation of brain stem
  • Demyelinating lesion (MS is diagnosed in 2-4% of patients with trigeminal neuralgia.)
  • Vascular insult
  • Migraine, cluster headache
  • Giant cell arteritis
  • Postherpetic neuralgia
  • Chronic meningitis
  • Acute polyneuropathy
  • Atypical odontalgia
  • SUNCT syndrome (short-lasting, unilateral, neuralgiform pain with conjunctival injection, and tearing)
DIAGNOSTIC TESTS & INTERPRETATION
  • The International Headache Society diagnostic criteria for classic trigeminal neuralgia (TN) are as follows:
    • Paroxysmal attacks of pain lasting from a fraction of 1 second to 2 minutes, affecting ≥ 1 divisions of the trigeminal nerve
    • Pain has at least an intense, sharp, superficial, or stabbing characteristic; or is precipitated from trigger areas or by trigger factors.
    • Attacks are stereotyped in the individual patient.
    • No clinically evident neurologic deficit found.
    • Not attributed to another disorder
  • Secondary TN is characterized by pain that is indistinguishable from classic TN but is caused by a demonstrable structural lesion other than vascular compression.
    • Indicated in all first-time-presenting patients to rule out secondary causes
  • MRI versus CT scan: MRI, with and without contrast, offers more detailed imaging and is preferred, if not contraindicated.
  • Routine head imaging identifies structural causes in up to 15% of patients.
  • No positive findings are significantly correlated with diagnosis.
Test Interpretation
  • Trigeminal nerve: inflammatory changes, demyelination, and degenerative changes
  • Trigeminal ganglion: hypermyelination and microneuromata
image TREATMENT
GENERAL MEASURES
  • Outpatient
  • Drug treatment is first approach.
  • Invasive procedures are reserved for patients who cannot tolerate, fail to respond to, or relapse after chronic drug treatment.
  • Avoid stimulation (e.g., air, heat, cold) of trigger zones, including lips, cheeks, and gums.
MEDICATION
First Line
  • Carbamazepine (Tegretol) (1)[A]: Start at 100 to 200 mg BID; effective dose usually 200 mg QID; max dose 1,200 mg/day:
    • 70-90% of patients respond initially.
    • By 3 years, 30% are no longer helped (number needed to treat [NNT] = 1.7) (1)[A]
    • Most common side effect: sedation
  • Contraindications: concurrent use of monoamine oxidase inhibitors (MAOIs)
  • Precautions: caution in the presence of liver disease
  • Significant possible medication interactions: macrolide antibiotics, oral anticoagulants, anticonvulsants, tricyclics, oral contraceptives, steroids, digitalis, isoniazid, MAOIs, methyprylon, nabilone, nizatidine, other H2 blockers, phenytoin, propoxyphene, benzodiazepines, and calcium channel blockers
  • Oxcarbazepine (Trileptal): Start at 150 to 300 mg BID; effective dose usually 375 mg BID; max dose 1,200 mg/day:
    • Efficacy similar to carbamazepine
    • Faster, with less drowsiness and fewer drug interactions than carbamazepine
    • May cause hyponatremia
    • Most common side effect: sedation
Second Line
  • Antiepileptic drugs: Insufficient evidence from randomized, controlled trials to show significant benefit from antiepileptic drugs in TN (2)[A].
  • Phenytoin (Dilantin): 300 to 400 mg/day (synergistic with carbamazepine):
    • Potent P450 inducer (enhanced metabolism of many drugs)
    • Various CNS side effects (sedation, ataxia)
  • Baclofen (Lioresal): 10 to 80 mg/day; start at 5 to 10 mg TID with food (as an adjunct to phenytoin or carbamazepine); side effects: drowsiness, weakness, nausea, vomiting
  • Gabapentin (Neurontin): Start at 100 mg TID or 300 mg at bedtime; can increase dose up to 300 to 600 mg TID-QID. Can be used as monotherapy or in combination with other medications and reduces the cost of illness.
  • Lamotrigine: Titrate up to 200 mg BID over weeks; side effect: 10% experience rash
  • P.1063

  • Antidepressants, including amitriptyline, fluoxetine, trazodone:
    • Used especially with anticonvulsants
    • Particularly effective for atypical forms of TN
  • Clonazepam (Klonopin) frequently causes drowsiness and ataxia.
  • Sumatriptan (Imitrex) 3 mg SC reduces acute symptoms and may be helpful after failure of conventional medical therapy.
  • Capsaicin cream topically
  • Botulinum toxin injection into zygomatic arch
  • Valproic acid (Depakene, Depakote)
ISSUES FOR REFERRAL
Initial treatment failure or positive findings on imaging studies
ADDITIONAL THERAPIES
  • Radiotherapy
  • Stereotactic radiosurgery, such as gamma knife radiosurgery, has been shown to be effective after drug failure:
    • Produces lesions with focused gamma knife radiation
    • Therapy aimed at the proximal trigeminal root
    • Minimal clinically effective dose: 70 Gy
    • ˜ 60-80% of patients achieve complete relief within 1 year; by 3 years, ˜ 30-40% maintain complete relief (3)[B].
    • Most common side effect: sensory disturbance (facial numbness)
    • Failure rates are higher in patients with past TN-related invasive procedures.
SURGERY/OTHER PROCEDURES
  • Microvascular decompression of CN V at its entrance to (or exit from) brain stem:
    • 98% of patients achieve initial pain relief; by 20 months, 86% maintain complete relief (NNT = 2) (4)[B].
    • Surgical mortality across studies was 0.3-0.4%.
    • Most common side effect: transient facial numbness and diplopia, headache, nausea, vomiting
    • Pain relief after procedure strongly correlates with the type of TN pain: Type 1 (shocklike pain) results in better outcomes than type 2 (aching pain between paroxysms).
  • Peripheral nerve ablation (multiple methods):
    • Higher rates of failure and facial numbness than decompression surgery
    • Radiofrequency thermocoagulation
    • Neurectomy
    • Cryotherapy: high relapse rate
    • Partial sensory rhizotomy
  • 4% tetracaine dissolved in 0.5% bupivacaine nerve block (only a few case reports to date; ropivacaine)
  • Alcohol block or glycerol injection into trigeminal cistern: unpredictable side effects (dysesthesia and anesthesia dolorosa); temporary relief
  • Peripheral block or section of CN V proximal to Gasserian ganglion
  • Balloon compression of Gasserian ganglion
  • Evidence supporting destructive procedures for benign pain conditions remains limited (5)[A].
COMPLEMENTARY & ALTERNATIVE MEDICINE
Acupuncture, moxibustion (herb): weak evidence for efficacy (6)[B]
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Regular outpatient follow-up to monitor symptoms and therapeutic failure.
Patient Monitoring
  • Carbamazepine and/or phenytoin serum levels
  • If carbamazepine is prescribed: CBC and platelets at baseline, then weekly for a month, then monthly for 4 months, then every 6 to 12 months if dose is stable (regimens for monitoring vary)
  • Reduce drugs after 4 to 6 weeks to determine whether condition is in remission; resume at previous dose if pain recurs. Withdraw drugs slowly after several months, again to check for remission or if lower dose of drugs can be tolerated.
DIET
No special diet
PATIENT EDUCATION
  • Instruct patient regarding medication dosage and side effects, risk-to-benefit ratios of surgery, or radiation therapy.
  • Support organizations:
    • The Facial Pain Association (formerly the Trigeminal Neuralgia Association): www.fpa-support.org
    • Living with Trigeminal Neuralgia: www.livingwithtn.org
PROGNOSIS
  • 50-60% eventually fail pharmacologic treatment.
  • After having microvascular decompression surgery, most patients wish they had undergone the procedure sooner.
  • Of those, relapse is seen in ˜ 50% of stereotactic radiosurgeries and ˜ 27% of surgical microvascular decompressions.
REFERENCES
1. Wiffen PJ, Derry S, Moore RA, et al. Carbamazepine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014;(4):CD005451.
2. Zhang J, Yang M, Zhou M, et al. Non-antiepileptic drugs for trigeminal neuralgia. Cochrane Database Syst Rev. 2013;(12):CD004029.
3. Karam SD, Tai A, Wooster M, et al. Trigeminal neuralgia treatment outcomes following Gamma Knife radiosurgery with a minimum 3-year follow-up. J Radiat Oncol. 2014;3:125-130.
4. Sekula RF Jr, Frederickson AM, Jannetta PJ, et al. Microvascular decompression for elderly patients with trigeminal neuralgia: a prospective study and systematic review with meta-analysis. J Neurosurg. 2011;114(1):172-179.
5. Zakrzewska JM, Akram H. Neurosurgical interventions for the treatment of classical trigeminal neuralgia. Cochrane Database Syst Rev. 2011;(9):CD007312.
6. Liu H, Li H, Xu M, et al. A systematic review on acupuncture for trigeminal neuralgia. Altern Ther Health Med. 2010;16(6):30-35.
Additional Reading
&NA;
  • Attal N, Cruccu G, Baron R, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17(9):1113-e88.
  • Gronseth G, Cruccu G, Alksne J, 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.
Codes
&NA;
ICD10
  • G50.0 Trigeminal neuralgia
  • B02.22 Postherpetic trigeminal neuralgia
Clinical Pearls
&NA;
  • Patients with TN typically have a normal physical exam.
  • The long-term efficacy of pharmacotherapy for TN is 40-50%.
  • If pharmacotherapy fails, stereotactic radiosurgery or surgical microvascular decompression often is successful.