1. Aetna considers the following surgical procedures for the treatment of trigeminal neuralgia medically necessary when the condition has persisted for at least 6 months despite conservative treatment with pharmacotherapies (carbamazepine, phenytoin, and baclofen) or the member is unable to tolerate the side effects of the medications. 

   1. Balloon compression
   2. Gamma knife (see CPB 0083 - Stereotactic Radiosurgery)
   3. Microvascular decompression
   4. Percutaneous glycerol rhizotomy (or injections)*
   5. Percutaneous radiofrequency rhizolysis/rhizotomy*
       

2. Aetna considers surgery for trigeminal neuralgia not meeting the afore-mentioned criteria experimental and investigational. 

3. Aetna considers pulsed radiofrequency for the treatment of trigeminal neuralgia experimental and investigational because its effectiveness has not been established (see CPB 0735 - Pulsed Radiofrequency).

4. Aetna considers motor cortex stimulation for the treatment of trigeminal neuralgia experimental and investigational because its effectiveness has not been established (see CPB 0755 - Motor Cortex Stimulation).

5. Aetna considers transection of the auriculo-temporal nerve, zygomatico-temporal nerve, and/or other branches of the mandibular nerve or trigeminal nerve for the treatment of trigeminal neuralgia experimental and investigational because its effectiveness has not been established.

6. Aetna considers percutaneous neuroablation experimental and investigational for the treatment of trigeminal neuralgia.

7. Aetna considers trigeminal nerve blocks medically necessary for refractory cases of trigeminal neuralgia.

8. Aetna considers electrical stimulation of the occipital nerve or trigeminal nerve experimental and investigational for the treatment of trigeminal neuralgia.

9. Aetna considers adipose-derived stem cells experimental and investigational for the treatment of trigeminal neuralgia because their effectiveness has not been established.

10. Aetna considers botulinum toxin experimental and investigational for the treatment of trigeminal neuralgia because its effectiveness has not been established.

* Note: These peripheral procedures refer to techniques that target portions of the trigeminal nerve distal to the Gasserian ganglion or techniques that target the Gasserian ganglion itself.

See also CPB 0707 - Headaches: Invasive Procedures.

Trigeminal neuralgia (TN), also known as tic douloureux, is a neuropathic pain syndrome characterized by paroxysmal, triggered, trigeminally distributed pain.  It affects more women than men (3:1 ratio), and is more common in the elderly.  The anti-epileptic drug carbamazepine (Tegretol) is the drug of choice for the management of TN.  Tegretol, at a dose of 600 to 1,200 mg per day, has been demonstrated to inhibit or shorten the duration of attacks.  Phenytoin (Dilantin), is also effective in treating TN, but less so than carbamazepine.  For patients who can not tolerate carbamazepine because of its adverse side effects (poor liver function, confusion, ataxia, drowsiness, and allergic responses), baclofen and other anti-convulsant drugs such as clonazepam (Klonopin) may be useful.  If pharmacotherapy fails, surgical intervention may be necessary.

Surgical treatment can be divided into 2 categories: (i) percutaneous, and (ii) open.  The former approaches include radiofrequency rhizolysis, glycerol injection, and balloon compression techniques.  The principal open approach is microvascular decompression, which entails posterior fossa craniotomy and has a small incidence of serious neurological morbidity.  In general, elderly or medically debilitated patients, patients with multiple sclerosis, or individuals who have failed to attain pain relief from the open approach are encouraged to use the percutaneous approaches, while the open approach is recommended for younger and healthier subjects.

The gamma knife, one type of stereotactic radiosurgery, is also used as a means of treating patients with TN.  It was developed in the 1950's by Larsson and Leksell, and is primarily used as a non-invasive alternative treatment for certain types of brain lesions such as intra-cranial arteriovenous malformations and brain tumors.  When the gamma knife is used to treat TN, the beams are focused on the root of the trigeminal nerve.  The stereotactic coordinates of the target site are often determined by computed tomography and/or magnetic resonance imaging.  Patients undergoing gamma knife radiosurgery are usually given local anesthesia with a mild sedative.

Pulsed radiofrequency (PRF) treatment entails the application of short bursts of RF energy to nervous tissue.  It is a minimally destructive procedure that may serve as an alternative to traditional RF heat lesion.  In a review on PRF treatment, Gallagher (2006) stated that "we should cautiously prescribe this promising intervention following clinical algorithms that are based upon the best clinical evidence available.  However, it is critically important to avoid the mistake of creating a "carte blanche" environment for those practitioners who would abuse the privilege and opportunity presented by this new technology, besmirching our credibility and ultimately impeding the opportunity to use this treatment to the benefit of the public.  Ultimately, evidence, not reimbursement, should determine whether PRF finds a place in our clinical toolbox".

Cahana et al (2006) stated that PRF, a non- or minimally-neurodestructive technique, has been used as alternative to radiofrequency heat lesions.  Clinical advantages and mechanisms of PRF remain unclear.  These investigators reviewed current clinical and laboratory data on PRF.  The final analysis yielded 58 reports on the clinical use of PRF in different applications: 33 full publications and 25 abstracts.  They also retrieved 6 basic science reports, 5 full publications, and 1 abstract.  The authors concluded that the accumulation of these data showed that the use of PRF generates an increasing interest of pain physicians for the management of a variety of pain syndromes.  Although the mechanism of action has not been completely elucidated, laboratory reports suggested a genuine neurobiological phenomenon altering the pain signaling, which some researchers have described as neuromodulatory.  No side effects related to PRF were reported to date.  They stated that further research in the clinical and biological effects of this technique is justified.

In the only controlled clinical trial of PRF for TN published to date, Erdine et al (2007) concluded that PRF is not an effective treatment for TN.  Erdine et al (2007) reported on a prospective, randomized, double-blinded study to compare PRF to conventional radiofrequency (CRF) in the treatment of idiopathic TN.  A total of 40 patients with idiopathic TN were randomly assigned to PRF or CRF.  Visual Analog Scale (VAS) scores decreased significantly (p < 0.001) and Patient Satisfaction Scale (PSS) scores improved significantly (p < 0.001) after the procedure in subjects assigned to CRF.  The VAS score decreased in only 2 of 20 patients from the PRF group and pain recurred 3 months after the procedure.  The investigators reported that, at the end of 3 months, they performed CRF in patients assigned to PRF, because all patients in this group still had intractable pain.

Cheshire (2007) staetd that many treatments have been developed for TN.  Anti-epileptic drugs are superior to traditional analgesics with carbamazepine being the drug of first choice.  Additional drugs for which there is evidence of efficacy include oxcarbazepine, baclofen, gabapentin, lamotrigine and phenytoin.  However, many patients eventually experience tachyphylaxis or may not tolerate effective doses.  Surgical interventions include microvascular decompression; balloon compression; RF thermocoagulation or glycerol rhizotomies; and subcutaneous alcohol branch blockade.  Stereotactic gamma knife radiosurgery is a further option.  Motor cortex stimulation and transcranial magnetic stimulation, although having shown initial promise for trigeminal neuropathic pain, seem to be ineffective for classical TN.

The Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies' practice parameter on the diagnostic evaluation and treatment of TN (Gronseth et al, 2008) stated that for patients with TN refractory to medical therapy, Gasserian ganglion percutaneous techniques, gamma knife, and microvascular decompression may be considered.

Adler et al (2009) stated that although stereotactic radiosurgery is an established procedure for treating TN, the likelihood of a prompt and durable complete response is not assured.  Moreover, the incidence of facial numbness remains a challenge.  To address these limitations, a new, more anatomic radiosurgical procedure was developed that uses the CyberKnife (Accuray, Inc., Sunnyvale, CA) to lesion an elongated segment of the retro-Gasserian cisternal portion of the trigeminal sensory root.  Because the initial experience with this approach resulted in an unacceptably high incidence of facial numbness, a gradual dose and volume de-escalation was performed over several years.  In this single-institution prospective study, these researchers assessed clinical outcomes in a group of TN patients who underwent lesioning with seemingly optimized non-isocentric radiosurgical parameters.  A total of 46 patients with intractable idiopathic TN were treated between January 2005 and June 2007.  Eligible patients were either poor surgical candidates or had failed previous microvascular decompression or destructive procedures.  During a single radiosurgical session, a 6-mm segment of the affected nerve was treated with a mean marginal prescription dose of 58.3 Gy and a mean maximal dose of 73.5 Gy.  Monthly neurosurgical follow-up was performed until the patient became pain-free.  Longer-term follow-up was performed both in the clinic and over the telephone.  Outcomes were graded as excellent (pain-free and off medication), good (greater than 90 % improvement while still on medication), fair (50 to 90 % improvement), or poor (no change or worse).  Facial numbness was assessed using the Barrow Neurological Institute Facial Numbness Scale score.  Symptoms disappeared completely in 39 patients (85 %) after a mean latency of 5.2 weeks.  In most of these patients, pain relief began within the first week.  Trigeminal neuralgia recurred in a single patient after a pain-free interval of 7 months; all symptoms abated after a second radiosurgical procedure.  Four additional patients underwent a repeat rhizotomy after failing to respond adequately to the first operation.  After a mean follow-up period of 14.7 months, patient-reported outcomes were excellent in 33 patients (72 %), good in 11 patients (24 %), and poor/no improvement in 2 patients (4 %).  Significant ipsilateral facial numbness (Grade III on the Barrow Neurological Institute Scale) was reported in 7 patients (15 %).  The authors concluded that optimized non-isocentric CyberKnife parameters for TN treatment resulted in high rates of pain relief and a more acceptable incidence of facial numbness than reported previously.  Moreover, they stated that longer follow-up periods will be needed to establish whether or not the durability of symptom relief after lesioning an elongated segment of the trigeminal root is superior to isocentric radiosurgical rhizotomy.

Fariselli et al (2009) reported the safety and effectiveness and safety of CyberKnife robotic radiosurgery as a first-line treatment against pharmacologically refractory TN.  These investigators treated 33 patients with the frameless CyberKnife system as a monotherapy.  The retro-Gasserian portion of the trigeminal nerve (a length of 4 mm, 2 to 3 mm anterior to the root entry zone) was targeted. Doses of 55 to 75 Gy were prescribed to the 100 % isodose line, according to a dose escalation protocol.  Patients were evaluated for the level of pain control, time to pain relief, hypesthesia, and time to pain recurrence.  The median age was 74 years.  All but 2 patients (94 %) achieved a successful treatment outcome.  The follow-up period was 9 to 37 months (mean of 23 months).  The Barrow Neurological Institute Pain Intensity Scale (BPS) score before radiosurgery was III in 2 patients (6 %), IV in 8 patients (24 %), and V in 23 patients (70 %).  The time to pain relief was 1 to 180 days (median of 30 days).  No facial numbness was observed. Only 1 patient developed a transitory dysesthesia of the tongue.  After treatment, the BPS score was I, II, or III in 31 patients (97 %).  Pain recurred in 33 % (11 patients) at a mean of 9 months (range of 1 to 43 months).  Three patients with recurrences had low pain control by medication (BPS score, IV), and 1 patient (BPS score, V) needed a RF lesioning (BPS score, I at 12 months).  The authors concluded that CyberKnife radiosurgery for TN allows pain relief at safe doses and is suggested for pharmacologically refractory TN.  It should be noted that the rate of pain recurrence is rather high in this study (33 %).

Kouzounias et al (2010) compared percutaneous balloon compression (PBC) and percutaneous retrogasserian glycerol rhizotomy (PRGR) for the treatment of TN in terms of effectiveness, complications, and technical aspects.  A total of 66 consecutive PBC procedures were performed in 45 patients between January 2004 and December 2008, and 120 PRGR attempts were performed in 101 patients between January 2006 and December 2008.  The PRGR procedures were not completed due to technical reasons in 19 cases.  Five patients in the PBC group and 9 patients in the PRGR group were lost to follow-up and were excluded from the study.  The medical records as well as the intra-operative fluoroscopic images from the remaining cases were retrospectively examined, and the follow-up was completed with telephone contact, when necessary.  The 2 groups were compared in terms of initial effect, duration of effect, and rates of complications as well as severity and type of complications.  The rates for immediate pain relief were 87 % for patients treated with glycerol injection and 85 % for patients treated with balloon compression.  The Kaplan-Meier plots for the 2 treatment modalities were similar.  The 50 % recurrence time was 21 months for the balloon procedure and 16 months for the glycerol procedure.  When the groups were broken down by the "previous operations" criterion, the 50 % recurrence time was 24 months for the Glycerol First Procedure Group, 6 months for the Balloon First Procedure Group, 8 months for the Glycerol Previous Procedures Group, and 21 months for the Balloon Previous Procedures Group.  The rates of complications (excluding numbness) were 11 % for PRGR and 23 % for PBC, and this difference was statistically significant (chi-square test, p = 0.04).  The authors concluded that both PRGR and PBC are effective techniques for the treatment of TN, with PRGR presenting some advantages in terms of milder and fewer complications and allowing lighter anesthesia without compromise of analgesia.  For these reasons the authors consider PRGR as the first option for the treatment of TN in patients who are not suitable candidates or are not willing to undergo microvascular decompression, while PBC is reserved for patients in whom the effect of PRGR has proven to be short or difficult to repeat due to cisternal fibrosis.

A Cochrane review on “Neurosurgical interventions for the treatment of classical trigeminal neuralgia” (Zakrzewska and Akram, 2011) noted that surgical treatments for refractory trigeminal neuralgia are divided into 2 main categories: (i) ablative (destructive) and (ii) non-ablative.  These treatments can be done at 3 different sites: (i) peripherally, (ii) at the Gasserian ganglion level, and (iii) within the posterior fossa of the skull.  The authors concluded that “There is very low quality evidence for the effectiveness of most neurosurgical procedures for trigeminal neuralgia because of the poor quality of the trials.  All procedures produced variable pain relief, but many resulted in sensory side effects …. Well-designed studies are urgently needed”.

An UpToDate review on "Trigeminal neuralgia" (Bajwa et al, 2013) states that “Peripheral neurectomy can be performed on the branches of the trigeminal nerve, which are the supraorbital, infraorbital, alveolar, and lingual nerves.  Neurectomy is accomplished by incision, alcohol injection, radiofrequency lesioning, or cryotherapy.  Cryotherapy involves freezing of the nerve using special probes, in theory to selectively destroy the pain fibers.  The AAN/EFNS practice parameter noted that the evidence regarding peripheral techniques for the treatment of TN is either negative or inconclusive”.

Collet et al (2013) stated that the etiology of TN remains unclear and several theories have been proposed.  Many medical and surgical methods have been applied with only partial effectiveness and several side effects.  New hypotheses and therapeutic methods are urgently needed.  Using evidence presented in a literature review and in the authors’ case report, these researchers hypothesized that pain resulting from TN can be caused by demyelinating lesions in the trigger zone.; and that these lesions can be repaired through the injection of fat containing adipose-derived stem cells.

Parmar et al (2013) stated that pharmacotherapy still remains the first line therapy for the management of TN.  However, often the patients become refractory to the pharmacotherapy and need surgical interventions.  There is a wide array of surgical treatment modalities available for TN.  These investigators evaluated the various surgical modalities by employing a comparative analysis with respect to patient selection, success rate, complications and cost-effectiveness.  For the evaluation, a critical review of literature was done with pre-defined search terms to obtain the details of individual procedures, which were then compared, under similar parameters.  The results suggested that microvascular decompression seem to be the most effective treatment in terms of patient satisfaction and long term cost-effectiveness.  However, if patient factors do not permit, then the peripheral procedures may be employed as a substitute, though they have higher recurrence rate and complications and have relatively lower long-term cost effectiveness.  The authors noted that newer modalities like stereotactic radiosurgery and botulinum toxin have promising results and further refinement in these procedures will provide additional options for the patients suffering from TN.

Hu and colleagues (2013) systematically reviewed the therapeutic safety and effectiveness of botulinum toxin type A (BTX-A) in the treatment of TN.  PubMed, EMBASE, Cochrane Library Clinical Trials and Web of Science from January 1966 to March 2013 were searched with the terms of "botulinum toxin" and "trigeminal neuralgia", and references of related articles were traced.  Data on the safety and effectiveness of BTX-A in this disorder were extracted and analyzed by at least 2 reviewers.  Data for individual studies were reported, and pooled data were analyzed if appropriate.  A total of 5 prospective studies and 1 double-blind, randomized, placebo-controlled study were identified.  Response was achieved in approximately 70 to 100 % of patients, and the mean pain intensity and frequency were reduced by approximately 60 to 100 % at 4 weeks after treatment in most studies.  Major adverse events were not reported.  Available studies showed BTX-A may be effective in treatment of TN.  However, the authors concluded that well-designed randomized, controlled, double-blinded trial is still lacking.  They stated that future BTX-A treatment studies on optimal dose, duration of the therapeutic effectiveness, common adverse events, and the time and indications for repeat injection would be promising.

Fontaine et al (2013) stated that although most patients suffering from TN respond to medical or surgical treatment, non-responders remain in very severe painful condition.  These researchers described for the first time a case of severe refractory classical TN treated successfully (follow-up 1 year) by chronic bilateral occipital nerve stimulation (ONS), because other classic medical and surgical options failed or could not be performed.  The authors concluded that this single case suggested that ONS might be offered to TN patients who are refractory both to standard drugs and interventions, with a favorable risk/benefit ratio, although its long-term effectiveness remains unknown.  This preliminary finding needs to be validated by well-designed studies.