Headaches: Invasive Procedures

Number: 0707

Policy

1. Aetna considers the following interventions experimental and investigational for the treatment of cervicogenic headache because their effectiveness for this indication has not been established:

   1. Botulinum toxin (however, botulinum toxin is considered medically necessary for chronic migraine headache when criteria in CPB 0113 - Botulinum Toxin are met)
   2. C2 ganglion nerve block
   3. Cryodenervation
   4. Decompressive neck surgery
   5. Electrical stimulation
   6. Ganglionectomy 
   7. Local injections of anesthetics or corticosteroids
   8. Radiofrequency denervation of cervical facet joints

2. Aetna considers the following interventions experimental and investigational for the treatment of occipital neuralgia and other types of headache because their effectiveness for this indication has not been established:

   1. Auriculotemporal nerve block
   2. Cervical rhizotomy
   3. Cryodenervation
   4. Decompression or microdecompression of the occipital nerves
   5. Dorsal column stimulation (see CPB 0194 - Spinal Cord Stimulation)
   6. Electrical stimulation of the occipital nerve (examples of devices for occipital nerve stimulation are ONSTIM and PRISM)
   7. Ganglionectomy
   8. Intradural rhizotomy
   9. Neurectomy
   10. Neurolysis of the great occipital nerve with or without section of the inferior oblique muscle
   11. Neuroplasty
   12. Occipital nerve block (also known as occipital infiltration)
   13. Pulsed radiofrequency ablation (see CPB 0735 - Pulsed Radiofrequency)
   14. Radiofrequency ablation (including the occipital nerve) / radiofrequency denervation / radiofrequency neurotomy
   15. Resection or partial resection of muscle or tissue from the forehead, peri-orbital, occipital or other facial or scalp areas
   16. Resection or partial resection of the semispinalis capitus muscle
   17. Supraorbital nerve block
   18. Suprascapular nerve block
   19. Surgical release of the lesser occipital nerve within the trapezius and other procedures to decompress occipital nerves
   20. Transection/avulsion of the occipital nerve
   21. Thermal neurolysis (thermal and cryodenervation)
        

3. Aetna considers surgery and the following interventions experimental and investigational for the treatment of cluster headache and other chronic headaches including migraines because their effectiveness for these indications has not been established.  Surgical interventions include some of the procedures listed below (not an all-inclusive list):

   • Ablation or electrical stimulation or topical anesthesia of the sphenopalatine ganglion (sphenopalatine ganglion block//sphenopalatine nerve block)
   • Bariatric surgery
   • Closure of patent foramen ovale
   • Decompression of the greater occipital, supra-orbital and supra-trochlear nerves
   • Deep brain stimulation
   • Gamma knife (stereotactic) radiosurgery
   • Nerve decompression
   • Occipital nerve stimulation
   • Resection of the right and left supra-orbital, supra-trochlear and infra-trochlear nerves
   • Resection of musculature, including but not limited to the corrugator supercilii muscle, or any soft tissue from the forehead, peri-orbital, occipital or other facial or scalp areas; manipulation or repositioning of any muscle or other soft tissue within these areas
   • Resection of any portion of the trigeminal nerve or its branches
   • Sensory nerve decompression
   • Sphenopalatine nerve block
   • Spinal accessory nerve block
   • Stellate ganglion block
   • Suboccipital nerve stimulation 
   • Supraorbital nerve stimulation
   • Topical anesthesia of the sphenopalatine ganglion
   • Transposition of cranial sensory nerves
   • Trigeminal nerve block
   • Vascular ligation of superficial extracranial arteries.
     
     
4. Aetna considers subcutaneous peripheral nerve field stimulation for the treatment of nummular headache experimental and investigational because the effectiveness of this approach has not been established.

Note: For closure of patent foramen ovale for migraine prophylaxis, see CPB 0292 - Transcatheter Closure of Septal Defects.

Background

A number of procedures or treatments have been proposed for headaches and occipital neuralgia, including injections/blocks, ablative techniques, occipital nerve stimulation, peripherally implanted nerve stimulation or surgical procedures.  

Injection therapy delivers local anesthetics, steroids or other agents into the region of the affected nerve(s) thereby reducing pain and inflammation. Examples of injections/blocks used to treat headaches or occipital neuralgia include, but may not be limited to, occipital nerve block, greater occipital nerve block, C2 ganglion nerve block, sphenopalantine nerve block, stellate ganglion block, supraorbital nerve block or supratrochlear nerve block.

Ablative procedures (eg, pulsed radiofrequency ablation, radiofrequency ablation, radiofrequency denervation, radiofrequency neurotomy, cryodenervation, neurolysis, rhizotomy) may be performed in attempt to denervate the occipital nerve (greater or lesser), upper cervical nerve (eg, second cervical nerve, also known as C2), supraorbital, supratrochlear or sphenopalatine ganglion. The proposed goal of denervation is to "shut off" the pain signals that are sent to the brain from the nerves. An additional purported objective is to reduce the likelihood of, or to delay, any recurrence that may occur by selectively destroying pain fibers without causing excessive sensory loss, motor dysfunction or other complications.

Surgical interventions are proposed as a treatment option to relieve impingement of the nerve root(s) and thereby eliminate symptoms caused by compression and injury to the cervical nerves. Examples of surgical interventions include, but may not be limited to, occipital nerve decompression, microdecompression of the occipital nerve, transection/avulsion of the occipital nerve, resection/partial resection of the semispinalis capitus muscle, neuroplasty, sensory nerve decompression, transposition of cranial sensory nerve or ganglionectomy. Another surgical approach is vascular ligation of superficial extracranial arteries (eg, superficial branches of the external carotid artery, main trunk of the superficial temporal artery, frontal branch of the superficial temporal artery, occipital artery or posterior auricular artery) which are theorized as an origin of headache pain in some individuals.

Cervicogenic Headache

Cervicogenic headache (CGH) is a relatively common and still controversial form of headache caused by disease or dysfunction of structures in the cervical spine (e.g., congenital anomalies of the cranio-vertebral junction such as basilar invagination, and atlanto-axial dislocation; injury of the ligaments, muscles, or joints of the neck).  It can be triggered by vascular or scar tissue compression of the C2 root and ganglion as well as irritation of other upper cervical nerve roots (e.g., C3, C4).  In patients with CGH, attacks or chronic fluctuating periods of neck/head pain may be provoked and/or worsened by sustained neck movements or stimulation of ipsilateral tender points.  There are no diagnostic imaging techniques of the cervical spine and associated structures that can determine the exact source of pain.  Although it has been advocated by some headache clinicians that the use of nerve blocks is an important confirmatory evidence for diagnosing CGH, the standardization of diagnostic nerve blocks in the diagnosis of CGH remains to be defined.  Differential diagnoses of CGH include hemicrania continua, chronic paroxysmal hemicrania, occipital neuralgia, migraine headache and tension headache.  Moreover, there is considerable overlap in symptoms and findings between CGH and migraine/tension headaches.

A curative treatment for CGH is unlikely to be developed until the etiology of this disorder has been elucidated.  Since CGH appears to be refractory to common headache medication, other treatments have been used in the management of CGH.  These entail non-invasive therapies such as  paracetamol and non-steroidal anti-inflammatory drugs; manual modalities and transcutaneous electrical nerve stimulation; local injections of anesthetic, corticosteroids, or botulinum toxin type A (Botox); as well as invasive surgical therapies such as decompression and radiofrequency lesions of the involved nerve structures (Jansen, 2000; Haldeman and Dagenais, 2001; Martelletti and van Suijlekom, 2004).

In a Cochrane review, Langevin et al (2011) evaluated the literature on the treatment effectiveness of botulinum toxin (BoNT) intra-muscular injections for neck pain, disability, global perceived effect and quality of life in adults with neck pain with or without associated cervicogenic headache, but excluding cervical radiculopathy and whiplash associated disorder.  These researchers included randomized and quasi-randomized controlled trials in which BoNT injections were used to treat sub-acute or chronic neck pain.  A minimum of 2 review authors independently selected articles, abstracted data, and assessed risk of bias, using the Cochrane Back Review Group criteria.  In the absence of clinical heterogeneity, these investigators calculated standardized mean differences (SMD) and relative risks, and performed meta-analyses using a random-effects model.  The quality of the evidence and the strength of recommendations were assigned an overall grade for each outcome.  They included 9 trials (503 subjects).  Only BoNT type A (BoNT-A) was used in these studies.  High quality evidence suggested there was little or no difference in pain between BoNT-A and saline injections at 4 weeks (5 trials; 252 subjects; SMD pooled -0.07 (95 % confidence intervals ([CI]: -0.36 to 0.21)) and 6 months for chronic neck pain.  Very low quality evidence indicated little or no difference in pain between BoNT-A combined with physiotherapeutic exercise and analgesics and saline injection with physiotherapeutic exercise and analgesics for patients with chronic neck pain at 4 weeks (2 trials; 95 subjects; SMD pooled 0.09 [95 % CI: -0.55 to 0.73]) and 6 months (1 trial; 24 subjects; SMD -0.56 [95 % CI: -1.39 to 0.27]).  Very low quality evidence from 1 trial (32 subjects) showed little or no difference between BoNT-A and placebo at 4 weeks (SMD 0.16 [95 % CI: -0.53 to 0.86]) and 6 months (SMD 0.00 [95 % CI: -0.69 to 0.69]) for chronic cervicogenic headache.  Very low quality evidence from 1 trial (31 subjects), showed a difference in global perceived effect favouring BoNT-A in chronic neck pain at 4 weeks (SMD -1.12 [95 % CI: -1.89 to -0.36]).  The authors concluded that current evidence fails to confirm either a clinically important or a statistically significant benefit of BoNT-A injection for chronic neck pain associated with or without associated cervicogenic headache.  Likewise, there was no benefit seen for disability and quality of life at 4 week and 6 months.

In a review on CGH, Pollmann et al (1997) stated that neither pharmacological nor surgical or chiropractic procedures lead to a significant improvement or remission of CGH.  These investigators concluded that until controlled studies on large and homogeneous groups of patients are performed, operative intervention can not be recommended for CGH.  Edmeads (2001) noted that although expertly administered local anesthetic blocks applied in a rational fashion can be of diagnostic value, their value as treatment for CGH is much less clear.  Furthermore, Evers (2004) stated that for the prophylactic treatment of migraine headache, tension headache, and CGH, no sufficient positive evidence for treatment with Botox is obtained from randomized, double-blind, placebo-controlled trials to date.

Stovner et al (2004) reported on the results of a randomized, double-blind, placebo-controlled study of radiofrequency denervation of facet joints C2 through C6 in cervicogenic headache.  A total of 12 patients with disabling, long-standing and treatment-resistant unilateral headache were randomly assigned to receive either sham treatment or radiofrequency neurotomy of facet joints C2 through C6 ipsilateral to the pain.  Patients were followed for 2 years by self-assessed pain ratings, measurements of sensitivity to pain and neck mobility measurements for two years following treatment.  The investigators reported that subjects treated with neurotomy were somewhat improved by 3 months after treatment, but later there were no marked differences between groups.  This led the investigator to conclude that radiofrequency denervation of cervical facet joints is probably not beneficial in cervicogenic headache.

Occipital Neuralgia

Occipital neuralgia, occurring more often in women than men, is defined as a paroxysmal jabbing pain in the distribution of the greater or lesser occipital nerves.  It is characterized by pain in the cervical and posterior areas of the head that may/may not radiate to the sides of the head as well as into the facial and frontal areas.  Occipital neuralgia can arise as a result of compression of the greater or lesser occipital nerves, trauma (e.g., whiplash), localized infections or inflammation, gout, diabetes, blood vessel inflammation and local tumors.  It may occur as the nerves exit the trapezii or splenius muscle groups.  Compression of these nerves may result in a burning dysasthesias in the occiput with or without radiation behind the ear.  Nerve compression can occur from cervical degeneration or post-traumatic compression of the C2 or C3 nerves.  The clinical features of the condition are pain and sensory change in the distribution of the relevant nerve, localized nerve trunk tenderness.  Clinical signs and symptoms of occipital neuralgia may also be produced by myofascial pain.

Treatments for occipital neuralgia ranges from rest, heat, massage, exercise, antidepressants, nerve blocks, neurectomy, cervical rhizotomy, surgical release of the occipital nerve within the trapezius to neurolysis of the great occipital nerve with or without section of the inferior oblique muscle.  However, the effectiveness of many of the invasive procedures has not been firmly established.

Graff-Radford (2001) stated that neurectomy has been employed for occipital neuralgia, but the results are often short-lived.  Barolat and Sharan (2000) stated that one of the applications being developed for spinal cord stimulation is occipital neuralgia.

There is a lack of evidence that local injection therapy such as steroids, botulinum toxin and local anesthetics or surgical such as decompression of the C2 nerve root, implantation of spinal cord stimulator, neurolysis of the great occipital nerve and surgical release of the occipital nerve within the trapezius consistently provide sustained pain relief in the majority of patients with CGH and occipital neuralgia.  Furthermore, there is also a lack of information regarding which patients might obtain significant benefit from these procedures.

Recently, there has been increased interest in subcutaneous electrical stimulation of the occipital nerve for the treatment of occipital neuralgia.  Kapural et al (2005) reported a case series of 6 patients with severe occipital neuralgia who underwent occipital nerve electrical stimulation lead implantation using a modified midline approach. These patients had received conservative and surgical therapies in the past including oral anti-depressants, membrane stabilizers, opioids, occipital nerve blocks, and radiofrequency ablations.  Significant decreases in pain VAS scores and drastic improvement in functional capacity were observed during the occipital stimulation trial and during the 3-month follow-up after implantation.  The mean VAS score changed from 8.66 +/- 1.0 to 2.5 +/- 1.3 whereas pain disability index improved from 49.8 +/- 15.9 to 14.0 +/- 7.4.  These findings need to be validated by randomized controlled studies.

Electrical stimulation of the occipital nerve is also being investigated for the treatment of chronic migraine headaches.  However, there is currently a lack of evidence regarding its effectiveness for this indication.

Slavin et al (2006) analyzed records of 14 consecutive patients (9 women and 5 men; mean age of 43.3 years) with intractable occipital neuralgia (ON) treated with peripheral nerve stimulation (PNS).  Five patients had unilateral and 9 had bilateral PNS electrodes inserted for trial, which was considered successful if patient reported at least 50 % decrease of pain on the visual analogue scale.  Ten patients proceeded with system internalization, and their long-term results were analyzed.  At the time of the last follow-up examination (5 to 32 months, mean of 22 months), 7 patients (70 %) with implanted PNS systems continue to experience beneficial effects of stimulation, including adequate pain control, continuous employment, and decrease in oral pain medications intake.  Two patients had their systems explanted because of loss of stimulation effect or significant improvement of pain, and 1 patient had part of his hardware removed because of infection.  The authors concluded that overall, the beneficial effect from chronic stimulation in their series persisted in more than 50 % of the patients for whom procedure was considered and in 80 % of those who significantly improved during the trial and proceeded with internalization.  Thus, chronic PNS may be a safe and relatively effective method for long-term treatment of chronic pain syndrome in patients with medically intractable ON.  The results of this small study are promising, but they need to be validated by further investigation.

An interventional procedure consultation from the National Institute for Health and Clinical Excellence (NICE, 2008) concluded: "Current evidence on the safety and efficacy of occipital nerve stimulation for intractable headache is inadequate in both quantity and quality.  Therefore this procedure should only be used with special arrangements for clinical governance, consent and audit or research."

Kapural et al (2007) retrospectively described a series of 6 patients with severe occipital neuralgia who received conservative and interventional therapies, including oral anti-depressants, membrane stabilizers, opioids, and traditional occipital nerve blocks without significant relief.  This group then underwent occipital nerve blocks using the botulinum toxin type A (BoNT-A) Botox type A (50 U for each block; 100 U if bilateral).  Significant decreases in pain VAS scores and improvement in Pain Disability Index (PDI) were observed at 4 weeks follow-up in 5 out of 6 patients following BoNT-A occipital nerve block.  The mean VAS score changed from 8 +/- 1.8 (median score of 8.5) to 2 +/- 2.7 (median score of 1), while PDI improved from 51.5 +/- 17.6 (median of 56) to 19.5 +/- 21 (median of 17.5) and the duration of the pain relief increased to an average of 16.3 +/- 3.2 weeks (median of 16) from an average of 1.9 +/- 0.5 weeks (median of 2) compared to diagnostic 0.5 % bupivacaine block.  Following block resolution, the average pain scores and PDI returned to similar levels as before BoNT-A block.  The authors concluded that BoNT-A occipital nerve blocks provided a much longer duration of analgesia than diagnostic local anesthetics.  The functional capacity improvement measured by PDI was profound enough in the majority of the patients to allow patients to resume their regular daily activities for a period of time.  This was a retrospective, small study with short-term follow-up; its findings need to be validated by well-designed studies.

In a review on greater occipital nerve blockade, Selekler (2008) stated that studies regarding greater occipital nerve injection in primary headaches began with Michael Anthony and almost all the studies today accept Anthony's studies as reference work.  Although more than 20 years had passed, there is insufficient information about this procedure.  According to available evidence, steroids are apparently effective in both preventive as well as therapy (for acute attack) in cluster headaches.  Effectiveness of occipital nerve blocks for the treatment of migraine headaches is not as dramatic as that observed for cluster headaches.  Despite the fact that local anesthetics has a role in relieving acute attacks, single injection is unsuitable as prophylasis.  The authors concluded that although there are case reports regarding the effectiveness of occipital nerve blocks in relieving acute pain in cluster headaches and migraine headaches, there is a need for systematized clinical studies.

An American Headache Society Information Paper "Information for Healthcare Professionals: Peripheral Nerve Blocks for Headaches" (Robbins & Blumenfeld, 2012) provides descriptive information about these blocks and includes three literature citations (Ashkenazi & Levin, 2007; Ashkenazi, Blumenfeld, et al, 2010; Blumenfeld, Ashkenazi, et al., 2010). A review article by Ashkenazi & Levin (2007) stated: “Several studies suggested efficacy of GON [greater occipital nerve] block in the treatment of migraine, cluster headache, and chronic daily headache. However, few were controlled and blinded. Despite a favorable clinical experience, little evidence exists for the efficacy of GON block in migraine treatment. Controlled studies are needed to better assess the role of GON block in the treatment of migraine and other headaches. . . . Despite favorable clinical experience, there is currently little convincing evidence for the efficacy of GON block in the acute or preventive treatment of headache. Most data on this topic come from non-controlled studies. Given the potentially high placebo effect that injections to the head have on the degree of pain, these data should be taken with reservation. Well-designed controlled studies are needed to better assess the role of GON block in headache treatment, to determine the patient populations who would benefit the most from this procedure, and to establish the optimal drug combination to use for nerve blockade.”  

The AHA Information Paper also cites Expert Consensus Recommendations for the Performance of Peripheral Nerve Blocks for Headaches (Blumenfeld & Ashkenazi, et al., 2010). As the title suggests, this article focuses primarily on recommendations on the proper performance of peripheral nerve blocks for headaches.  Regarding the indications for peripheral nerve blocks, the article refers readers to a literature review by Ashkenazi, Blumenfeld, et al. (2010), which is discussed below. 

A literature review by Ashkenazi, Blumenfeld, et al. (2010), also cited in the AHA Information Paper, concluded: “Our literature review reveals paucity of controlled data on the efficacy of PNBs and TPIs in headache management. Few studies have addressed this issue, and the majority of those that did had significant limitations, including a small number of patients, a retrospective, non-controlled design, and heterogeneous groups of patients. In addition, the studies that have been done so far differ in the technique used for nerve blockade, the type and doses of local anesthetics used, the injected volume, the location and number of injections, the time intervals between injection sessions, and the way treatment efficacy was assessed. Clearly, there is a need to obtain more data on the efficacy of these treatments in the management of various headache disorders in order to formulate a standardized approach to their use in headache patients.” Specifically regarding the effectiveness of occipital nerve blocks, the review concluded: “The most widely examined procedure in this setting was greater occipital nerve block, with the majority of studies being small and non-controlled.”

An editorial accompanying this systematic review (Blumenfeld & Ashkenazi, Editorial, 2010) stated: “As the review article demonstrates, however, there is a surprising paucity of controlled studies to support the efficacy of these treatments for headache. Moreover, the different studies reveal an inconsistency in the methods used to block the targeted nerves; the type of local anesthetics used, their doses, the volume of injected drug, and even the location of injections have varied considerably among the studies. While some investigators used corticosteroids in addition to local anesthetics to block the nerves, others did not. Clearly, there is a need for more work in this area, and hopefully the articles in this issue will stimulate additional interest and lead to the performance of larger and well-controlled studies.”

Dach et al (2015) noted that several studies have presented evidence that blocking peripheral nerves is effective for the treatment of some headaches and cranial neuralgias, resulting in reduction of the frequency, intensity, and duration of pain.  These investigators described the role of nerve block in the treatment of headaches and cranial neuralgias, and the experience of a tertiary headache center regarding this issue.  They also reported the anatomical landmarks, techniques, materials used, contra-indications, and side effects of peripheral nerve block, as well as the mechanisms of action of lidocaine and dexamethasone.  The authors concluded that the nerve block can be used in primary (migraine, cluster headache, and nummular headache) and secondary headaches (cervicogenic headache and headache attributed to craniotomy), as well in cranial neuralgias (trigeminal neuropathies, glossopharyngeal and occipital neuralgias).  In some of them this procedure is necessary for both diagnosis and treatment, while in others it is an adjuvant treatment.  The block of the greater occipital nerve with an anesthetic and corticosteroid compound has proved to be effective in the treatment of cluster headache.  Regarding the treatment of other headaches and cranial neuralgias, controlled studies are still needed to clarify the real role of peripheral nerve block. 

An UpToDate review stated: "For patients with suspected occipital neuralgia who have moderate to severe pain or debilitating symptoms, we suggest a local occipital nerve block (Grade 1B). This method can be both diagnostic and therapeutic. Pain relief is typically prompt and may last several weeks or even months. The procedure is generally safe and can be repeated when pain recurs. Other causes for the neuralgiform pain should be explored if occipital nerve block fails." 

Ducic et al (2009) presented the largest reported series of surgical neurolysis of the greater occipital nerve in the management of occipital neuralgia.  A retrospective chart review was conducted to identify 206 consecutive patients undergoing neurolysis of the greater or, less commonly, excision of the greater and/or lesser occipital nerves.  Pre-operative and post-operative VAS and migraine headache indices were measured.  Success was defined as a reduction in pain of 50 % or greater.  Of 206 patients, 190 underwent greater occipital nerve neurolysis (171 bilateral); 12 patients underwent greater and lesser occipital nerve excision, whereas 4 underwent lesser occipital nerve excision alone.  The authors found that 80.5 % of patients experienced at least 50 % pain relief and 43.4 % of patients experienced complete relief of headache.  Mean pre-operative pain score was 7.9 +/- 1.4.  Mean post-operative pain was 1.9 +/- 1.8.  Minimum duration of follow-up was 12 months.  There were 2 minor complications.  The authors concluded that neurolysis of the greater occipital nerve appears to provide safe, durable pain relief in the majority of selected patients with chronic headaches caused by occipital neuralgia.  The drawbacks of this study were the retrospective, uncontrolled, and non-blinded nature of the study.  Well-designed studies are especially important for studying interventions for pain, due to placebo effects, the waxing and waning nature of the condition, and the potential effects of other concurrent treatments on the person's pain.

In a prospective, randomized cross-over study, Serra and Marchioretto (2012) investigated the safety and effectiveness of occipital nerve stimulation (ONS) for chronic migraine (CM) and medication overuse headache (MOH) patients and evaluated changes in disability, quality of life, and drug intake in implanted patients.  Eligible patients who responded to a stimulation trial underwent device implantation and were randomized to "Stimulation On" and "Stimulation Off" arms.  Patients crossed-over after 1 month, or when their headaches worsened.  Stimulation was then switched On for all patients.  Disability as measured by the Migraine Disability Assessment (MIDAS), quality of life (SF-36), and drug intake (patient's diary) were assessed over a 1-year follow-up.  A total of 34 patients (76 % women, 34 % men, mean age of 46 +/- 11 years) were enrolled; 30 were randomized and 29 completed the study.  Headache intensity and frequency were significantly lower in the On arm than in the Off arm (p < 0.05) and decreased from the baseline to each follow-up visit in all patients with Stimulation On (median MIDAS A and B scores: baseline = 70 and 8; 1-year follow-up = 14 and 5, p < 0.001).  Quality of life significantly improved (p < 0.05) during the study.  Triptans and non-steroidal anti-inflammatory drug use fell dramatically from the baseline (20 and 25.5 doses/month) to each follow-up visit (3 and 2 doses/month at 1 year, p < 0.001).  A total of 5 adverse events occurred: 2 infections and 3 lead migrations.  The authors concluded that according to the results obtained, ONS appears to be a safe and effective treatment for  carefully selected CM and MOH patients.  The drawbacks of this study were single-center study, relatively small number of patients, and absence of a control group.  The authors stated that further analyses on larger populations in multi-center trials may strengthen these promising findings.

Vadivelu et al (2012) reviewed retrospectively their experience with ONS in patients with a primary diagnosis of Chiari malformation and a history of chronic occipital pain intractable to medical and surgical therapies.  They presented a retrospective analysis of 22 patients with Chiari malformation and persistent occipital headaches who underwent occipital neurostimulator trials and, after successful trials, permanent stimulator placement.  A trial was considered successful with greater than 50 % pain relief as assessed with a standard VAS score.  Patients with a successful trial underwent permanent placement approximately 1 to 2 weeks later.  Patients were assessed post-operatively for pain relief via the VAS.  Sixty-eight percent of patients (15 of 22) had a successful stimulator trial and proceeded to permanent implantation.  Of those implanted, 87 % (13 of 15) reported continued pain relief at a mean follow-up of 18.9 months (range of 6 to 51 months).  Device-related complications requiring additional surgeries occurred in 40 % of patients.  The authors concluded that ONS may provide significant long-term pain relief in selected Chiari I malformation patients with persistent occipital pain.  Moreover, they stated that larger and longer-term studies are needed to further define appropriate patient selection criteria and to refine the surgical technique to minimize device-related complications.

Acar et al (2008) noted that surgical removal of the second (C2) or third (C3) cervical sensory dorsal root ganglion is an option to treat occipital neuralgia (ON).  These investigators evaluated the short-term and the long-term effectiveness of these procedures for management of cervical and occipital neuropathic pain.  A total of 20 patients (mean age of 48.7 years) were identified who had undergone C2 and/or C3 ganglionectomies for intractable occipital pain and a retrospective chart review undertaken.  Patients were interviewed regarding pain relief, pain relief duration, functional status, medication usage and procedure satisfaction, pre-operatively, immediately post-operative, and at follow-up (mean of 42.5 months).  C2, C3 and consecutive ganglionectomies at both levels were performed on 4, 5, and 11 patients, respectively.  All patients reported pre-operative pain relief following cervical nerve blocks.  Average VAS scores were 9.4 pre-operatively and 2.6 immediately after procedure.  Ninety-five percent of patients reported short-term pain relief (less than 3 months).  In 13 patients (65 %), pain returned after an average of 12 months (C2 ganglionectomy) and 8.4 months (C3 ganglionectomy).  Long-term results were excellent, moderate, and poor in 20, 40 and 40 % of patients, respectively.  Cervical ganglionectomy offers relief to a majority of patients, immediately after procedure, but the effect is short-lived.  Nerve blocks are helpful in predicting short-term success, but a positive block result does not necessarily predict long-term benefit and therefore can not justify surgery by itself.  However, since 60 % of patients report excellent-moderate results, cervical ganglionectomy continues to have a role in the treatment of intractable ON.  The findings of this small study need to be validated by well-designed studies.

Pisapia and colleagues (2012) examined the effectiveness of C2 nerve root decompression and C2 dorsal root ganglionectomy for intractable ON and C2 ganglionectomy after pain recurrence following initial decompression.  A retrospective review was performed of the medical records of patients undergoing surgery for ON.  Pain relief at the time of the most recent follow-up was rated as excellent (headache relieved), good (headache improved), or poor (headache unchanged or worse).  Telephone contact supplemented chart review, and patients rated their pre-operative and post-operative pain on a 10-point numeric scale.  Patient satisfaction and disability were also examined.  Of 43 patients, 29 (67 %) were available for follow-up after C2 nerve root decompression (n = 11), C2 dorsal root ganglionectomy (n = 10), or decompression followed by ganglionectomy (n = 8).  Overall, 19 of 29 patients (66 %) experienced a good or excellent outcome at most recent follow-up.  Among the 19 patients who completed the telephone questionnaire (mean follow-up of 5.6 years), patients undergoing decompression, ganglionectomy, or decompression followed by ganglionectomy experienced similar outcomes, with mean pain reduction ratings of 5 +/- 4.0, 4.5 +/- 4.1, and 5.7 +/- 3.5.  Of 19 telephone responders, 13 (68 %) rated overall operative results as very good or satisfactory.  The authors concluded that in the third largest series of surgical intervention for ON, most patients experienced favorable post-operative pain relief.  For patients with pain recurrence after C2 decompression, salvage C2 ganglionectomy is a viable surgical option and should be offered with the potential for complete pain relief and improved quality of life.  Only 10 patients with C2 dorsal root ganglionectomy were available for follow-up.  The moderate rate of follow-up (67 %) may have skewed these results.

Also, UpToDate reviews on “Occipital neuralgia” (Garza, 2012) and “Cervicogenic headache” (Biondi and Bajwa, 2012) do not mention the use of cryo-denervation and ganglionectomy.

The supraorbital nerve is located on the front of the face over the eyebrow. It supplies sensory innervation to the upper eyelid, forehead, and scalp, extending almost to the lambdoidal suture. A nerve block is a procedure in which an anesthetic agent is injected directly near a nerve to block pain. It is a form of regional anesthesia. 

In a randomized controlled trial (RCT), Liu and co-workers (2017) evaluated the effectiveness and tolerability of transcutaneous ONS (tONS) in patients with migraine, and examined if different tONS frequencies influenced treatment effectiveness.  Patients were randomized to 1 of 5 therapeutic groups prior to treatment for 1 month.  Groups A to C received tONS at different frequencies (2-Hz, 100-Hz, and 2/100-Hz), group D underwent sham tONS intervention, and group E received topiramate orally.  The primary outcomes were the 50 % responder rate and headache characteristics.  A total of 110 patients completed the study.  The 50 % responder rate was significantly greater in the groups undergoing active tONS and topiramate, compared with sham-treated group.  A significant reduction in headache intensity was noted in each test group compared with the sham group; the groups undergoing tONS at different frequencies did not differ significantly.  From baseline to the 1-month treatment period, tONS group with 100-Hz and topiramate group exhibited significant decreases in headache duration.  The authors concluded that tONS therapy is a new promising approach for migraine prevention.  It has infrequent and mild adverse events (AEs) and may be effective among patients who prefer non-pharmacological treatment.

Neurolysis

Choi and Jeon (2016) stated that occipital neuralgia is defined by the International Headache Society as paroxysmal shooting or stabbing pain in the dermatomes of the greater or lesser occipital nerve.  Various treatment methods exist, from medical treatment to open surgical procedures.  Local injection with corticosteroid can improve symptoms, though generally only temporarily.  More invasive procedures can be considered for cases that do not respond adequately to medical therapies or repeated injections.  Radiofrequency lesioning of the greater occipital nerve can relieve symptoms, but there is a tendency for the pain to recur during follow-up.  There also remains a substantial group of intractable patients that do not benefit from local injections and conventional procedures.  Moreover, treatment of occipital neuralgia is sometimes challenging.  More invasive procedures, such as C2 gangliotomy, C2 ganglionectomy, C2 to C3 rhizotomy, C2 to C3 root decompression, neurectomy, and neurolysis with or without sectioning of the inferior oblique muscle, are now rarely performed for medically refractory patients.  Recently, a few reports have described positive results following peripheral nerve stimulation of the greater or lesser occipital nerve.  Although this procedure is less invasive, the significance of the results is hampered by the small sample size and the lack of long-term data.  Clinicians should always remember that destructive procedures carry grave risks: once an anatomic structure is destroyed, it cannot be easily recovered, if at all, and with any destructive procedure there is always the risk of the development of painful neuroma or causalgia, conditions that may be even harder to control than the original complaint.

This review cited 3 retrospective studies (n = 206, n = 10, and n = 18, respectively) on the use of nerve neurolysis for the treatment of occipital neuralgia.  Moreover, it stated that neurolysis of the occipital nerve (with or without sectioning of the inferior oblique muscle), C2 gangliotomy, C2 ganglionectomy, C2 to C3 rhizotomy, C2 to C3 root decompression, and neurectomy were historically introduced for medically refractory patients.  However, the results were variable … Of these approaches, both occipital neurolysis and occipital nerve stimulation (ONS) have been used commonly in the clinical field, recently.  In selective cases, these methods have shown good outcomes, but a well-designed randomization study with a long-term observation is not yet available.

Intradural Rhizotomy

Kapoor and associates (2003) described CT fluoroscopy-guided percutaneous C2 to C3 nerve block for the confirmation of diagnosis of ON and for demonstrating to patients the sensory effects of intradural cervical dorsal rhizotomy (CDR) before the definitive surgical procedure.  A total of 17 patients with ON underwent 32 CT fluoroscopy-guided C2 or C2 and C3 nerve root blocks.  Of the 17 patients, 9 had ON following prior neck or skull base surgeries.  On the basis of the positive results of the nerve blocks in terms of temporary pain relief, all 17 patients underwent unilateral (n = 16) or bilateral (n = 1) intradural C1 (n = 9), C2 (n = 17), C3 (n = 17), or C4 (n = 7) dorsal rhizotomies.  All patients were followed-up for a mean of 20 months (range of 5 to 37) for assessment of pain relief; 16 patients were assessed for degree of satisfaction with and functional state after surgery.  All patients had temporary relief of symptoms after percutaneous CT-guided block (positive result) and felt that occipital numbness was an acceptable alternative to pain.  Immediately after surgery, all patients had complete relief from pain.  At follow-up, 11 patients (64.7 %) had complete relief of symptoms, 2 (11.8 %) had partial relief, and 4 (23.5 %) had no relief; 7 of 8 (87.5 %) patients without prior surgery had complete relief of symptoms and 1 (12.5 %) patient had partial relief, as opposed to complete relief in 4 of 9 (44.4 %), partial relief in 1 of 9 (11.2 %), and no relief in 4 of 9 (44.4 %) patients with a history of prior surgery.  Because of the small number of patients, this difference was not statistically significant (p = 0.110); 11 of 16 (68.8 %) patients stated that the surgery was worthwhile; 8 of 16 (50 %) patients felt they were more active and functional after surgery, whereas 25 % felt they were either unchanged or less functional than before surgery.  None of the patients without a history of prior surgery reported a decreased sense of functional activity following rhizotomy.  The authors concluded that CT fluoroscopy-guided percutaneous cervical nerve block was useful for the confirmation of ON, for demonstrating to patients the sensory effects of nerve sectioning, and possibly as a guide for selection of patients for intradural CDR.  Moreover, they noted that although not statistically significant, there was a trend toward better response to rhizotomy in patients without prior head or neck surgery.

Gande and colleagues (2016) noted that the long-term effectiveness of CDR in the management of ON has not been well described.  In a retrospective chart-review study, these researchers reviewed their 14-year experience with CDR to evaluate pain relief and functional outcomes in patients with medically refractory ON.  A total of 75 ON patients who underwent CDR from 1998 to 2012 were included in this analysis; 55 patients were included because they met the International Headache Society's (IHS) diagnostic criteria for ON, responded to CT-guided nerve blocks at the C2 dorsal nerve root, and had at least 1 follow-up visit.  Telephone interviews were additionally used to obtain data on patient satisfaction; 42 patients (76 %) were women, and the average age at surgery was 46 years (range of 16 to 80).  Average follow-up was 67 months (range of 5 to 150).  Etiologies of ON included the following: idiopathic (44 %), post-traumatic (27 %), post-surgical (22 %), post-cerebrovascular accident (4 %), post-herpetic (2 %), and post-viral (2 %).  At last follow-up, 35 patients (64 %) reported full pain relief, 11 (20 %) partial relief, and 7 (16 %) no pain relief.  The extent of pain relief after CDR was not significantly associated with ON etiology (p = 0.43).  Of 37 patients whose satisfaction-related data were obtained, 25 (68 %) reported willingness to undergo repeat surgery for similar pain relief, while 11 (30 %) reported no such willingness; a single patient (2 %) did not answer this question; 21 individuals (57 %) reported that their activity level/functional state improved after surgery, 5 (13 %) reported a decline, and 11 (30 %) reported no difference.  The most common acute post-operative complications were infections in 9 % (n = 5) and CSF leaks in 5 % (n = 3); chronic complications included neck pain/stiffness in 16 % (n = 9) and upper-extremity symptoms in 5 % (n = 3) such as trapezius weakness, shoulder pain, and arm paresthesias.  The authors concluded that CDR provided an effective means for pain relief in patients with medically refractory ON.  In the appropriately selected patient, it may lead to optimal outcomes with a relatively low risk of complications.  Moreover, the authors noted a number of drawbacks, including the retrospective nature of the study, the lack of comparison groups, not using a validated tool to quantify pain, and lack of follow-up in 1/3 of subjects to confirm pain relief.  They stated that a larger prospective study with regular follow-up and comparison with other treatment modalities is needed to confirm  the effectiveness of CDR.

Choi and Jeon (2016) stated that more invasive procedures, such as C2 gangliotomy, C2 ganglionectomy, C2 to C3 rhizotomy, C2 to C3 root decompression, neurectomy, and neurolysis with or without sectioning of the inferior oblique muscle, are now rarely performed for medically refractory patients.

Furthermore, an UpToDate review on “Occipital neuralgia” (Garza, 2017) does not mention intradural rhizotomy as a therapeutic option.

Cluster Headache

Cluster headaches are characterized by repeated attacks of severe headache usually occurring several times a day.  Patients with chronic cluster headache have unremitting illness that requires daily preventive medical treatment for years.  Burns et al (2007) examined the effectiveness of occipital nerve stimulation (ONS) in the treatment of patients with refractory chronic cluster headache (n = 8).  Electrodes were implanted in the suboccipital region for ONS.  Other than the first patient, who was initially stimulated unilaterally before being stimulated bilaterally, all patients were stimulated bilaterally during treatment.  At a median follow-up of 20 months (range of 6 to 27 months for bilateral stimulation), 6 of 8 patients reported responses that were sufficiently meaningful for them to recommend the treatment to similarly affected patients with chronic cluster headache.  Two patients noticed a substantial improvement (90 % and 95 %) in their attacks; 3 patients noticed a moderate improvement (40 %, 60 %, and 20 to 80 %, respectively) and 1 reported mild improvement (25 %).  Improvements occurred in both frequency and severity of attacks.  These changes took place over weeks or months, although attacks returned in days when the device malfunctioned (e.g., with battery depletion).  Adverse effects were lead migrations in 1 patient and battery depletion requiring replacement in 4.  The authors concluded that ONS in cluster headache seems to offer a safe, effective treatment option that could begin a new era of neurostimulation therapy for primary headache syndromes.

In a pilot study, Magis et al (2007) evaluated the effectiveness of ONS in the treatment of patients with drug-resistant chronic cluster headache (drCCH).  A total of 8 patients with drCCH had a sub-occipital neurostimulator implanted on the side of the headache and were asked to record details of frequency, intensity, and symptomatic treatment for their attacks in a diary before and after continuous ONS.  To detect changes in cephalic and extra-cephalic pain processing, these researchers measured electrical and pressure pain thresholds and the nociceptive blink reflex.  Two patients were pain-free after a follow-up of 16 and 22 months; 1 of them still had occasional autonomic attacks.  Three patients had around a 90 % reduction in attack frequency.  Two patients, 1 of whom had had the implant for only 3 months, had improvement of around 40 %.  Mean follow-up was 15.1 months (standard deviation of 9.5, range of 3 to 22 months).  Intensity of attacks tends to decrease earlier than frequency during ONS and, on average, is improved by 50 % in remaining attacks.  All but 1 patient were able to substantially reduce their preventive drug treatment.  Interruption of ONS by switching off the stimulator or because of an empty battery was followed within days by recurrence and increase of attacks in all improved patients.  Occipital nerve stimulation did not significantly modify pain thresholds.  The amplitude of the nociceptive blink reflex increased with longer durations of ONS.  There were no serious adverse events.  The authors concluded that ONS could be an efficient treatment for drCCH and could be safer than deep hypothalamic stimulation.  The delay of 2 months or more between implantation and significant clinical improvement suggests that the procedure acts via slow neuromodulatory processes at the level of upper brain stem or diencephalic centers.

In a retrospective analysis, Schwedt et al (2007) examined the safety and effectiveness of ONS for medically intractable headache.  Pre- and post-implantation data regarding headache frequency, severity, disability, depression and post-stimulator complications were collected.  A total of 15 patients (12 females and 3 males) with age ranging from 21 to 52 years (mean of 39 years) were included in this study.  Eight patients had chronic migraine, 3 chronic cluster, 2 hemicrania continua and 2 had post-traumatic headache.  Eight patients underwent bilateral and 7 had unilateral lead placement.  They were measured after 5 to 42 months (mean of 19 months).  All 6 mean headache measures improved significantly from baseline (p < 0.03).  Headache frequency per 90 days improved by 25 days from a baseline of 89 days; headache severity (0 to 10) improved 2.4 points from a baseline of 7.1 points; MIDAS disability improved 70 points from a baseline of 179 points; HIT-6 scores improved 11 points from a baseline of 71 points; BDI-II improved 8 points from a baseline of 20 points; and the mean subjective percent change in pain was 52 %.  Most patients (60 %) required lead revision within 1 year.  One patient required generator revision.  The authors concluded that ONS may be effective in some patients with intractable headache.  Surgical revisions may be commonly required.  They noted that safety and effectiveness results from prospective, randomized, sham-controlled studies in patients with medically refractory headache are needed to validate these preliminary findings.

Jasper and Hayek (2008) noted that there is limited evidence that ONS is a useful tool in the treatment of chronic severe headaches.  In a review on ONS for headache, Goadsby et al (2008) stated that far from proven and with much work to be done, neurostimulation therapy by means of ONS is an exciting potential development for patients and doctors.  Furthermore, Trentman and Zimmerman (2008) stated that ONS may be an effective minimally invasive treatment modality for refractory headache disorders; however, further studies are needed.

Burns et al (2009) described the clinical outcome of ONS for 14 patients with intractable CCH.  A total of 14 patients with medically intractable CCH were implanted with bilateral electrodes in the suboccipital region for ONS and a retrospective assessment of their clinical outcome wereobtained.  At a median follow-up of 17.5 months (range of 4 to 35 months), 10 of 14 patients reported improvement and 9 of these recommended ONS.  Three patients noticed a marked improvement of 90 % or better (90 %, 90 %, and 95 %, respectively), 3 a moderate improvement of 40 % or better (40 %, 50 %, and 60 %, respectively), and 4 a mild improvement of 20 to 30% (20 %, 20 %, 25 %, and 30 %, respectively).  Improvement occurred within days to weeks for those who responded most and patients consistently reported their attacks returned within hours to days when the device was off.  One patient found that ONS helped abort acute attacks.  Adverse events of concern were lead migrations and battery depletion.  The authors concluded that intractable CCH is a devastating, disabling condition that has traditionally been treated with cranially invasive or neurally destructive procedures.  Occipital nerve stimulation offers a safe, effective option for some patients with CCH.  However, they stated that more work is needed to evaluate and understand this novel therapy.

Narouze (2010) stated that cluster headache is a strictly unilateral head pain that is associated with cranial autonomic symptoms and usually follows circadian and circannual patterns.  Chronic cluster headache, which accounts for about 10 % to 15 % of patients with cluster headache, lacks the circadian pattern and is often resistant to pharmacological management.  The sphenopalatine ganglion (SPG), located in the pterygopalatine fossa, is involved in the pathophysiology of cluster headache and has been a target for blocks and other surgical approaches.  Percutaneous radiofrequency ablation of the SPG was shown to have encouraging results in those patients with intractable cluster headaches.

Ansarinia et al (2010) examined the effects of electrical stimulation of SPG for acute treatment of cluster headaches. A total fo 6 patients with refractory CCH were treated with short-term (up to 1 hour) electrical stimulation of the SPG during an acute cluster headaches.  Headaches were spontaneously present at the time of stimulation or were triggered with agents known to trigger clusters headache in each patient.  A standard percutaneous infra-zygomatic approach was used to place a needle at the ipsilateral SPG in the pterygopalatine fossa under fluoroscopic guidance.  Electrical stimulation was performed using a temporary stimulating electrode.  Stimulation was performed at various settings during maximal headache intensity.  Five patients had cluster headaches during the initial evaluation.  Three returned 3 months later for a second evaluation.  There were 18 acute and distinct cluster headache attacks with clinically maximal VAS intensity of 8 (out of 10) and above.  Electrical stimulation of SPG resulted in complete resolution of the headache in 11 attacks, partial resolution (greater than 50 % VAS reduction) in 3, and minimal to no relief in 4 attacks.  Associated autonomic features of cluster headache were resolved in each responder.  Pain relief was noted within several minutes of stimulation.  The authors concluded that SPG stimulation can be effective in relieving acute severe cluster headache pain and associated autonomic features.  They stated that chronic long-term outcome studies are needed to determine the utility of SPG stimulation for management and prevention of cluster headaches.

In a prospective, cross-over, double-blind, multi-center study, Fontaine et al (2010) evaluated the safety and effectiveness of unilateral hypothalamic deep brain stimulation (DBS) in 11 patients with severe refractory CCH.  The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase.  The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity, sumatriptan injections, emotional impact (HAD) and quality of life (SF12).  Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions.  During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation.  At the end of the open phase, 6/11 responded to the chronic stimulation (weekly frequency of attacks decrease [50 %]), including 3 pain-free patients.  There were 3 serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes.  No significant change in hormonal functions or electrolytic balance was observed.  Randomized phase findings of this study did not support the effectiveness of DBS in refractory CCH, but open phase findings suggested long-term effectiveness in more than 50 % patients, confirming previous data, without high morbidity.  Discrepancy between these findings justifies additional controlled studies.

Akram and colleagues (2016) presented outcomes in a cohort of medically intractable CCH patients treated with ventral tegmental area (VTA) DBS.  In an uncontrolled, open-label, prospective study, a total of  21 patients (17 men; mean age of 52 years) with medically refractory CCH were selected for ipsilateral VTA-DBS by a specialist multi-disciplinary team including a headache neurologist and functional neurosurgeon.  Patients had also failed or were denied access to ONS within the UK National Health Service.  The primary end-point was improvement in the headache frequency; secondary outcomes included other headache scores (severity, duration, headache load), medication use, disability and affective scores, quality of life (QOL) measures, and adverse events (AEs).  Median follow-up was 18 months (range of 4 to 60).  At the final follow-up point, there was 60 % improvement in headache frequency (p = 0.007) and 30 % improvement in headache severity (p = 0.001).  The headache load (a composite score encompassing frequency, severity, and duration of attacks) improved by 68 % (p = 0.002).  Total monthly triptan intake of the group dropped by 57 % post-treatment.  Significant improvement was observed in a number of QOL, disability, and mood scales.  Side effects included diplopia, which resolved in 2 patients following stimulation adjustment, and persisted in 1 patient with a history of ipsilateral trochlear nerve palsy.  There were no other serious AEs.  The authors concluded that the findings of this study suggested that VTA-DBS may be a safe and effective therapy for refractory CCH patients who failed conventional treatments.  This study provided Class IV evidence that VTA-DBS decreases headache frequency, severity, and headache load in patients with medically intractable CCH.  This was an open-label study; thus, a placebo effect cannot be excluded.  Well-designed studies are needed to validate these findings.

Other Headaches

Asensio-Samper and colleagues (2008) presented the case of a patient with headache because of post-traumatic supra-orbital neuralgia, refractory to medical treatment, with good analgesic control following peripheral nerve stimulation.  The authors stated that peripheral nerve stimulation may be considered a safe, reversible treatment for patients with headache secondary to supra-orbital neuralgia who respond poorly to pharmacological treatment, thus avoiding irreversible alternatives such as surgery.  Moreover, in a review on neurostimulation in chronic cluster headache, Magis and Schoenen (2008) noted that recent case reports mentioned effectiveness of supra-orbital and vagus nerve stimulation.  Whether these methods have a place in the management of patients with intractable chronic cluster headache remains to be determined.

Mathew (2009) stated that comparator studies that assess treatment effects in a clinical setting have improved the understanding of the efficacy and tolerability of prophylactic treatments for chronic migraine.  It is premature to recommend device-based treatments, such as ONS, vagal nerve stimulation, and patent foramen ovale closure for chronic migraine, because clinical trials are still in the preliminary stages.

Franzini et al (2009) stated that ONS is an emerging procedure for the treatment of cranio-facial pain syndromes and headaches refractory to conservative treatments.  Paemeleire and Bartsch (2010) stated that ONS was originally described in the treatment of occipital neuralgia.  However, the spectrum of possible indications has expanded in recent years to include primary headache disorders, such as migraine and cluster headaches.  Retrospective and some prospective studies have yielded encouraging results, and evidence from controlled clinical trials is emerging.  Moreover, these researchers noted that ONS is far from a standardized technique at the moment.  They reviewed the recent literature on the topic, both with respect to the procedure and its possible complications.  An important way to move forward in the scientific evaluation of occipital nerve stimulation to treat refractory headache is the clinical phenotyping of patients to identify patients groups with the highest likelihood to respond to this modality of treatment.  This requires multi-disciplinary assessment of patients.  The development of occipital nerve stimulation as a new treatment for refractory headache offers an exciting prospect to treat the most disabled headache patients.  Data from ongoing controlled trials will shed new light on some of the unresolved questions.

In a retrospective, descriptive study, Poggi et al (2008) evaluated the effectiveness of surgical decompression of multiple migraine trigger sites in a clinical practice setting, and compared the results to those previously published.  A total of 18 patients who had undergone various combinations of surgical decompression of the supraorbital, supratrochlear, and greater occipital nerves and zygomaticotemporal neurectomy  were included in this analysis.  All patients had been diagnosed with migraine headaches according to neurological evaluation and had undergone identification of trigger sites by botulinum toxin type A injections.  Following surgical decompression, the number of migraines per month and the pain intensity of migraine headaches decreased significantly.  Three patients (17 %) had complete relief of their migraines, and 9 of 18 (50 %) had at least a 75 % reduction in the frequency, duration, or intensity of migraines; and 39 % of patients have discontinued all migraine medications.  Mean follow-up was 16 months (range of 6 to 41 months) after surgery.  All subjects stated they would repeat the surgical procedure. The authors conclded that the findings of this study supported the theory that peripheral nerve compression triggers a migraine cascade.  They verified a reduction in duration, intensity, and frequency of migraine headaches by surgical decompression of the supraorbital, supratrochlear, zygomaticotemporal, and greater occipital nerves.  They stated that a significant amount of patient screening is needed for proper patient selection and trigger site identification for surgical success.  These findings need to be validated by well-designed studies.

Kung et al (2011) stated that migraine headache can be a debilitating condition that confers a substantial burden to the affected individual and to society.  Despite significant advancements in the medical management of this challenging disorder, clinical data have revealed a proportion of patients who do not adequately respond to pharmacologic intervention and remain symptomatic.  Recent insights into the pathogenesis of migraine headache argue against a central vasogenic cause and substantiate a peripheral mechanism involving compressed craniofacial nerves that contribute to the generation of migraine headache.  Botulinum toxin injection is a relatively new treatment approach with demonstrated efficacy and supports a peripheral mechanism.  Patients who fail optimal medical management and experience amelioration of headache pain after injection at specific anatomical locations can be considered for subsequent surgery to decompress the entrapped peripheral nerves.  Migraine surgery is an exciting prospect for appropriately selected patients suffering from migraine headache and will continue to be a burgeoning field that is replete with investigative opportunities.  The authors stated that future research will elucidate the anatomical relationships of migraine trigger points and possibly identify additional sites that have the capacities to generate migraines ... Research is currently being conducted to examine the long-term benefits of migraine surgery.

Magis and Schoenen (2011) reviewed the latest clinical trial results in anti-migraine treatment.  The oral calcitonine gene-related peptide antagonist telcagepant is effective in acute treatment.  Compared to triptans, its effectiveness is almost comparable but its tolerance is superior.  The same is true for the 5HT-1F agonist lasmiditan.  Triptans, as other drugs, are more efficient if taken early but NSAIDs and analgesics remain useful for acute treatment, according to several meta-analyses.  Single-pulse transcranial magnetic stimulation during the aura rendered more patients pain-free (39 %) than sham stimulation (22 %) in 1 study.  Topiramate could be effective for migrainous vertigo, but it did not prevent transformation to chronic migraine in patients with high attack frequency.  Onabotulinumtoxin A was effective for chronic migraine and well tolerated, but the therapeutic gain over placebo was modest; the clinical profile of responders remains to be determined before widespread use.  Occipital nerve stimulation was effective in intractable chronic migraine with 39 % of responders compared to 6 % after sham stimulation.  This and other neuromodulation techniques, such as sphenopalatine ganglion stimulation, are promising treatments for medically refractory patients; but large controlled trials are needed.  One study suggested that outcome of patent foramen ovale closure in migraine might depend on anatomic and functional characteristics.

In a prospective, observational study, Bond et al (2011) examined if weight loss after bariatric surgery is associated with improvements in migraine headaches.  A total of 24 patients who had migraine according to the ID-Migraine screener were assessed before and 6 months after bariatric surgery.  At both time points, patients had their weight measured and reported on frequency of headache days, average headache pain severity, and headache-related disability over the past 90 days via the Migraine Disability Assessment questionnaire.  Changes in headache measures and the relation of weight loss to these changes were assessed using paired-sample t tests and logistic regression, respectively.  Patients were mostly female (88 %), middle-aged (mean age of 39.3), and severely obese (mean body mass index of 46.6) at baseline.  Mean (+/- SD) number of headache days was reduced from 11.1 +/- 10.3 pre-operatively to 6.7 +/- 8.2 post-operatively (p < 0.05), after a mean percent excess weight loss (% EWL) of 49.4 %.  The odds of experiencing a greater than or equal to 50 % reduction in headache days was related to greater % EWL, independent of surgery type (p < 0.05).  Reductions in severity were also observed (p < 0.05) and the number of patients reporting moderate-to-severe disability decreased from 12 (50.0 %) before surgery to 3 (12.5 %) after surgery (p < 0.01).  The authors concluded that severely obese migraineurs experience marked alleviation of headaches following significant weight reduction via bariatric surgery.  They stated that future studies are needed to determine whether more modest, behaviorally produced weight losses can result in similar migraine improvements.  Limitations of this study included its observational nature, small number of patients, and the lack of a control group.  It would also be interesting to determine if there is a dose-response relationship (i.e., whether greater weight loss results in greater improvement).

Gaul et al (2011) noted that cluster headache is the most common type of trigemino-autonomic headache, affecting approximately 120,000 persons in Germany alone.  The attacks of pain are in the peri-orbital area on one side, last 90 minutes on average, and are accompanied by trigemino-autonomic manifestations and restlessness.  Most patients have episodic cluster headache; about 15 % have chronic cluster headache, with greater impairment of their quality of life.  The attacks often possess a circadian and seasonal rhythm.  Oxygen inhalation and triptans are effective acute treatment for cluster attacks.  First-line drugs for attack prophylaxis include verapamil and cortisone; alternatively, lithium and topiramate can be given.  Short-term relief can be obtained by the subcutaneous infiltration of local anesthetics and steroids along the course of the greater occipital nerve, although most of the evidence in favor of this is not derived from randomized clinical trials.  Patients whose pain is inadequately relieved by drug treatment can be offered newer, invasive treatments, such as deep brain stimulation in the hypothalamus (DBS) and bilateral ONS.  The authors concluded that pharmacotherapy for the treatment of acute attacks and for attack prophylaxis is effective in most patients.  For the minority who do not gain adequate relief, newer invasive techniques are available in some referral centers.  Definitive conclusions as to their value can not yet be drawn from the available data.

The Work Loss Data Institute’s clinical guideline on “Neck and upper back (acute & chronic)” (2011) listed greater occipital nerve block (diagnostic and therapeutic) as one of the interventions/procedures that are under study and are not specifically recommended.

The Institute for Clinical Systems Improvement's clinical practice guideline on "Diagnosis and treatment of headache" (2011) does not mention the use of decompression of the occipital/greater occipital, supra-orbital and supra-trochlear nerves.  Furthermore, an UpToDate review on "Overview of chronic daily headache" (Garza and Schwedt, 2012) does not mention the use of decompression of the occipital, supra-orbital and supra-trochlear nerves as a therapeutic option.

Saper et al (2011) presented preliminary safety and efficacy data on ONS in patients with medically intractable CM.  Eligible subjects received an occipital nerve block, and responders were randomized to adjustable stimulation (AS), pre-set stimulation (PS) or medical management (MM) groups.  Seventy-five of 110 subjects were assigned to a treatment group; complete diary data were available for 66.  A responder was defined as a subject who achieved a 50 % or greater reduction in number of headache days per month or a 3-point or greater reduction in average overall pain intensity compared with baseline.  Three-month responder rates were 39 % for AS, 6 % for PS and 0 % for MM.  No unanticipated adverse device events occurred.  Lead migration occurred in 12 of 51 (24 %) subjects.  The authors concluded that results of this feasibility study offer promise and should prompt further controlled studies of ONS in CM.

Strand et al (2011) evaluated the effectiveness of a microstimulator for chronic cluster headache.  Four patients with medically refractory chronic cluster headache underwent implantation of a unilateral Bion microstimulator.  In-person follow-up was conducted for 12 months after implantation, and a prospective follow-up chart review was carried out to assess long term outcome.  Three of the participants returned their headache diaries for evaluation.  The mean duration of chronic cluster headache was 14.3 years (range of 3 to 29 years).  Pain was predominantly or exclusively retro-ocular/peri-ocular.  One participant showed a positive response (greater than 50 % reduction in cluster headache frequency) at 3 months post-implant, while there were 2 responders at 6 months.  At least 1 of the participants continued to show greater than 60 % reduction in headache frequency at 12 months.  A chart review showed that at 58 to 67 months post-implant, all 3 participants reported continued use and benefit from stimulation.  No side-shift in attacks was noted in any participant.  Adverse events were limited to 2 participants with neck pain and/or cramping with stimulation at high amplitudes; one required revision for a faulty battery.  The authors concluded that unilateral occipital nerve stimulation, using a minimally invasive microstimulator, may be effective for the treatment of medically refractory chronic cluster headache.  This benefit may occur immediately after implantation, remain sustained up to 5 years after implantation, and occur despite the anterior location of the pain.  They stated that prospective, randomized controlled trials of occipital nerve stimulation (ONS) in chronic cluster headache should proceed.

Lambru and Matharu (2012) stated that advances in the management of headache disorders have meant that a substantial proportion of patients can be effectively treated with medical treatments.  However, a significant minority of these patients are intractable to conventional medical treatments.  Occipital nerve stimulation is emerging as a promising treatment for patients with medically intractable, highly disabling chronic headache disorders, including migraine, cluster headache and other less common headache syndromes.  Open-label studies have suggested that this treatment modality is effective and recent controlled trial data are also encouraging.  The procedure is performed using several technical variations that have been reviewed along with the complications, which are usually minor and tolerable.  The mechanism of action is poorly understood, though recent data suggest that ONS could restore the balance within the impaired central pain system through slow neuromodulatory processes in the pain neuromatrix.  While the available data are very encouraging, the ultimate confirmation of the utility of a new therapeutic modality should come from controlled trials before widespread use can be advocated; more controlled data are still needed to properly assess the role of ONS in the management of medically intractable headache disorders.  The authors concluded that future studies also need to address the variables that are predictors of response, including clinical phenotypes, surgical techniques and stimulation parameters.

Presently, the Food and Drug Administration (FDA) has not approved any device for ONS.  Clinical trials are currently underway for 2 ONS devices -- ONSTIM^® (Medtronic Neuro) and PRISM^® (Boston Scientific Corporation) -- to ascertain the safety and effectiveness of ONS for migraine headaches.

The Taiwan Headache Society’s treatment guidelines for “Acute and preventive treatment of cluster headache” (Chen et al, 2011) evaluated both the acute and the preventive treatments for cluster headache now being used in Taiwan, based on the principles of evidence- based medicine.  These investigators assessed the quality of clinical trials and levels of evidence, and referred to other treatment guidelines proposed by other countries.  Throughout several panel discussions, these researchers merged opinions from the subcommittee members and proposed a consensus on the major roles, recommended levels, clinical efficacy, adverse events and cautions of clinical practice regarding acute and preventive treatments of cluster headache.  The majority of Taiwanese patients have episodic cluster headaches, because chronic clusters are very rare.  Cluster headache is characterized by severe and excruciating pain which develops within a short time and is associated with ipsilateral autonomic symptoms.  Therefore, emergency treatment for a cluster headache attack is extremely important.  Within the group of acute medications currently available in Taiwan, the subcommittee determined that high-flow oxygen inhalation has the best evidence of effectiveness, followed by intra-nasal triptans.  Both are recommended as 1st-line medical treatments for acute attacks.  Oral triptans were determined to be 2nd-line medications.  For transitional prophylaxis, oral corticosteroids are recommended as the 1st-line medication, and ergotamine as the 2nd-line choice.  As for maintenance prophylaxis, verapamil has the best evidence and is recommended as the 1st-line medication.  Lithium, melatonin, valproic acid, topiramate and gabapentin are suggested as the 2nd-line preventive medications.  Surgical interventions, including ONS, DBS, radiofrequency block of the sphenopalatine ganglion, percutaneous radiofrequency rhizotomy and trigeminal nerve section, are invasive and their long-term effectiveness and adverse events are still not clear in Taiwanese patients; therefore, they are not recommended currently by the subcommittee.  The transitional and maintenance prophylactic medications can be used together to attain treatment effectiveness.  Once the maintenance prophylaxis achieves effectiveness, the transitional prophylactic medications can be tapered gradually.  The authors suggested corticosteroids be used within 2 weeks, if possible.  The duration of maintenance treatment depends on the individual patient's clinical condition, and the medications can be tapered off when the cluster period is over.

Also, the National Clinical Guideline Centre’s guideline on “Headaches: Diagnosis and management of headaches in young people and adults” (NICE, 2012) as well as the Institute for Clinical Systems Improvement’s clinical e guideline on “Diagnosis and treatment of headache” (Beithon et al, 2013) did not mention surgery as a therapeutic option.

Furthermore, an UpToDate review on “Chronic migraine” (Garza and Schwedt, 2014) states that “Occipital nerve stimulation -- There are inconsistent data from small randomized trials regarding the benefit of occipital nerve stimulation for the treatment of chronic migraine.  In the largest trial, there was no significant difference at 12 weeks for the primary endpoint, the percentage of patients that had a ≥ 50 percent reduction in mean daily pain score in the active compared with the control group.  However, there were statistically significant if modest improvements with active stimulation for a number of secondary endpoints, including the percentage of patients with a ≥ 30 percent reduction in mean daily pain score, and reduction in the mean number of headache days and migraine-related disability.  The findings from these reports are limited by concerns about blinding in the control (sham treatment) groups, given that active treatment causes paresthesia, and relatively high rates of complications, including lead migration in 14 to 24 percent of subjects.  Further trials are needed to determine if occipital nerve stimulation is a useful therapy for chronic migraine”.  This review also does not mention the use of surgical interventions as therapeutic options.

Lip and Lip (2014) identified the extent of patent foramen ovale prevalence in migraineurs and examined if closure of a patent foramen ovale would improve migraine headache.  An electronic literature search was performed to select studies between January 1980 and February 2013 that were relevant to the prevalence of patent foramen ovale and migraine, and the effects of intervention(s) on migraine attacks.  Of the initial 368 articles presented by the initial search, 20 satisfied the inclusion criteria assessing patent foramen ovale prevalence in migraineurs and 21 presented data on patent foramen ovale closure.  In case series and cohort studies, patent foramen ovale prevalence in migraineurs ranged from 14.6 % to 66.5 %.  Case-control studies reported a prevalence ranging from 16.0 % to 25.7 % in controls, compared with 26.8 % to 96.0 % for migraine with aura.  The extent of improvement or resolution of migraine headache attack symptoms varied.  In case series, intervention ameliorated migraine headache attack in 13.6 % to 92.3 % of cases.  One single randomized trial did not show any benefit from patent foramen ovale closure.  The overall data did not exclude the possibility of a placebo effect for resolving migraine following patent foramen ovale closure.  The authors concluded that this systematic review demonstrated firstly that migraine headache attack is associated with a higher prevalence of patent foramen ovale than among the general population.  Moreover, observational data suggested that some improvement of migraine would be observed if the patent foramen ovale were to be closed.  They stated that a proper assessment of any interventions for patent foramen ovale closure would require further large randomized trials to be conducted given uncertainties from existing trial data.

Ashkenazi et al (2010) stated that interventional procedures such as peripheral nerve blocks (PNBs) and trigger point injections (TPIs) have long been used in the treatment of various headache disorders.  There are, however, little data on their efficacy for the treatment of specific headache syndromes.  Moreover, there is no widely accepted agreement among headache specialists as to the optimal technique of injection, type, and doses of the local anesthetics used, and injection regimens.  The role of corticosteroids in this setting is also debated.  These researchers performed a PubMed search of the literature to find studies on PNBs and TPIs for headache treatment.  They classified the abstracted studies based on the procedure performed and the treated condition.  They found few controlled studies on the efficacy of PNBs for headaches, and virtually none on the use of TPIs for this indication.  The most widely examined procedure in this setting was greater occipital nerve block, with the majority of studies being small and non-controlled.  The techniques, as well as the type and doses of local anesthetics used for nerve blockade, varied greatly among studies.  The specific conditions treated also varied, and included both primary (e.g., migraine, cluster headache) and secondary (e.g., cervicogenic, post-traumatic) headache disorders.  Trigeminal (e.g., supra-orbital) nerve blocks were used in few studies.  Results were generally positive, but should be taken with reservation given the methodological limitations of the available studies.  The procedures were generally well-tolerated.  The authors concluded that there is a need to perform more rigorous clinical trials to clarify the role of PNBs and TPIs in the management of various headache disorders, and to aim at standardizing the techniques used for the various procedures in this setting.

The Institute for Clinical Systems Improvement’s clinical guideline on “Diagnosis and treatment of headache” (ICSI, 2013) did not mention trigeminal nerve block as a therapeutic option. 

Giblin et al (2014) described a case of cervicogenic headache with associated autonomic features and pain in a trigeminal distribution, all of which responded to 3rd occipital nerve radiofrequency ablation.  This study discussed the case of a 38-year old woman with history of migraines and motor vehicle accident.  Right third occipital nerve diagnostic blocks and radiofrequency lesioning were carried out.  Outcome measures included pain reduction; physical findings, including periorbital and mandibular facial swelling, tearing, conjunctival injection, and allodynia; and use of opioid and non-opioid pain medicines.  The patient had complete relief of her pain and autonomic symptoms, and was able to stop all pain medications following a dedicated third occipital nerve lesioning.  The authors concluded that this case illustrated the diagnostic and therapeutic complexity of cervicogenic headache and the overlap with other headache types, including trigeminal autonomic cephalgias and migraine.  It represented a unique proof of principle in that not only trigeminal nerve pain but also presumed neurogenic inflammation can be relieved by blockade of cervical nociceptive inputs.  They stated that further investigation into shared mechanisms of headache pathogenesis is warranted.

Ambrosini and Schoenen (2016) reviewed minimally invasive interventions targeting pericranial nerves that could be effective in patients with primary headaches who were refractory to conventional treatments.  The interventions entailed nerve blocks/infiltrations to the percutaneous implantation of neuro-stimulators as well as surgical decompression procedures.  These researchers analyzed the published data (PubMed) on their effectiveness and tolerability.  The authors concluded that there is clear evidence for a preventative effect of suboccipital injections of local anesthetics and/or steroids in cluster headache, while evidence for such an effect is weak in migraine.  Percutaneous ONS provided significant long-term relief in more than 50 % of drug-resistant CCH patients, but no sham-controlled trial has tested this.  The evidence that ONS has lasting beneficial effects in CM is at best equivocal.  Suboccipital infiltrations are quasi-devoid of side effects, while ONS is endowed with numerous, though reversible, AEs.  These investigators stated that claims that surgical decompression of multiple pericranial nerves is effective in migraine are not substantiated by large, rigorous, randomized and sham-controlled trials.

Cho and colleagues (2017) noted that although CM is a common disorder that severely impacts patient functioning and QOL, it is usually under-diagnosed, and treatment responses often remain poor even after diagnosis.  In addition, effective therapeutic options are limited due to the rarity of RCTs involving patients with CM.  These investigators discussed updated pharmacological, non-pharmacological, and neuro-stimulation therapeutic options for CM.  Pharmacological treatments include both acute and preventive measures.  While acute treatment options are similar between CM and episodic migraine (EM), preventive treatment with topiramate and botulinum toxin A exhibited efficacy in more than 2 RCTs.  In addition, several studies have revealed that behavioral interventions such as cognitive behavioral therapy, biofeedback, and relaxation techniques are associated with significant improvements in symptoms.  Thus, these therapeutic options are recommended for patients with CM, especially for refractory cases.  Neuro-stimulation procedures, such as ONS, supraorbital transcutaneous stimulation (e.g., Cefaly), non-invasive vagal nerve stimulation (VNS; e.g., gammaCore), and transcranial direct current stimulation, have shown promising results in the treatment of CM.  However, current studies on neuro-stimulation suffer from small sample size, no replication, or negative results.

Puledda and Goadsby (2017) reviewed current neuro-modulation treatments available for migraine therapy, both in the acute and preventive setting.  The published literature was reviewed for studies reporting the effects of different neuro-modulation strategies in migraine with and without aura.  The use of non-invasive: single pulse transcranial magnetic stimulation (SpringTMS), non-invasive VNS, supraorbital nerve stimulation, and transcranial direct current stimulation, as well as invasive methods such as ONS and sphenopalatine ganglion stimulation, were evaluated.  Available evidence showed that non-invasive techniques represent promising treatment strategies, whereas an invasive approach should only be used where patients are refractory to other preventives, including non-invasive methods.  The authors concluded that neuro-modulation is emerging as an exciting approach to migraine therapy, especially in the context of failure of commonly used medicines or for patients who do not tolerate common side effects.  They stated that more studies with appropriate blinding strategies are needed to confirm the results of these new therapeutic approaches.

Leone and Cecchini (2017) noted that in the past 10 years, a number of neuro-modulatory procedures have been introduced as treatment of chronic intractable headache patients when pharmacological treatments fail or are not well-tolerated.  Neuro-stimulation of peripheral and central nervous system has been carried out, and now, various non-invasive and invasive stimulation devices are available.  Non-invasive neuro-stimulation options include VNS, supraorbital stimulation and single-pulse transcranial magnetic stimulation; invasive procedures include ONS, sphenopalatine ganglion stimulation and hypothalamic DBS.  In many cases, results supporting their use were derived from open-label series and small controlled trial studies. The authors stated that a lack of adequate placebo hampered adequate RCTs.

Occipital Nerve Block for Chronic Migraine Headaches

Szperka and colleagues (2016) described current patterns of use of nerve blocks and trigger point injections for treatment of pediatric headache.  A survey was created in REDCap, and sent via email to the 82 members of the Pediatric and Adolescent Section of the American Headache Society in June 2015.  The survey queried about current practice and use of nerve blocks, as well as respondents' opinions regarding gaps in the evidence for use of nerve blocks in this patient population.  Forty-one complete, 5 incomplete, and 3 duplicate responses were submitted (response rate complete 50 %).  About 78 % of the respondents identified their primary specialty as Child Neurology, and 51 % were certified in headache medicine; 26 (63 %) respondents perform nerve blocks themselves, and 7 (17 %) refer patients to another provider for nerve blocks.  Chronic migraine with status migrainosus was the most common indication for nerve blocks (82 %), though occipital neuralgia (79 %), status migrainosus (73 %), chronic migraine without flare (70 %), post-traumatic headache (70 %), and new daily persistent headache (67 %) were also common indications.  The most commonly selected clinically meaningful response for status migrainosus was greater than or equal to 50 % reduction in severity, while for chronic migraine this was a greater than or equal to 50 % decrease in frequency at 4 weeks.  Respondents inject the following locations: 100 % inject the greater occipital nerve, 69 % lesser occipital nerve, 50 % supraorbital, 46 % trigger point injections, 42 % auriculo-temporal, and 34 % supra-trochlear.  All respondents used local anesthetic, while 12 (46 %) also use corticosteroid (8 bupivacaine only, 4 each lidocaine + bupivacaine, lidocaine + corticosteroid, bupivacaine + corticosteroid, lidocaine + bupivacaine + corticosteroid, and 2 lidocaine only).  The authors concluded that despite limited evidence, nerve blocks are commonly used by pediatric headache specialists.  There is considerable variability among clinicians as to injection site(s) and medication selection, indicating a substantial gap in the literature to guide practice, and supporting the need for further research in this area.

Kocer (2016) reported the effects of greater occipital nerve (GON) blocks on refractory CM headache.  A total of 9 patients who were receiving the conventionally accepted preventive therapies underwent treatment with repeated GON block to control CM resistant to other treatments.  GON blocking with lidocaine and normal saline mixture was administered by the same physician at hospital once-monthly (for 3 times in total).  Patients were assessed before the injection and every month thereafter for pain frequency and severity, number of times analgesics were used and any apparent adverse effects (AEs) during a 6-month follow-up; 8 of 9 patients reported a marked decrease in frequency and severity of migraine attacks in comparison to their baseline symptoms; 1 reported no significant change (not more than 50 %) from baseline and did not accept the 2nd injection; GON block resulted in considerable reduction in pain frequency and severity and need to use analgesics up to 3 months after the injection in the present cases.  The patients did not report any AEs.  The authors noticed a remarkable success with refractory CM patients.  They believed that this intervention can result in rapid relief of pain with the effects lasting for perhaps several weeks or even months.  Moreover, they stated that  further controlled clinical trials are needed to evaluate the effect of GON block in the treatment of refractory migraine cases.

In an uncontrolled, open-label, prospective study, Miller and associates (2016) evaluated the long-term efficacy, functional outcome and safety of occipital nerve stimulation (ONS) in patients with intractable chronic migraine patients (n= 53).  Patients were implanted in a single-center between 2007 and 2013; they had a mean age of 47.75 years (range of 26 to 70), and had suffered chronic migraine for around 12 years and had failed a mean of 9 (range of 4 to 19) preventative treatments prior to implant; 18 patients had other chronic headache phenotypes in addition to chronic migraine.  After a median follow-up of 42.00 months (range of 6 to 97) monthly moderate-to-severe headache days (i.e., days on which pain was more than 4 on the verbal rating score and lasted at least 4 hours) reduced by 8.51 days (p < 0.001) in the whole cohort, 5.80 days (p < 0.01) in those with chronic migraine alone and 12.16 days (p < 0.001) in those with multiple phenotypes including chronic migraine.  Response rate of the whole group (defined as a greater than 30 % reduction in monthly moderate-to-severe headache days) was observed in 45.3 % of the whole cohort, 34.3 % of those with chronic migraine alone and 66.7 % in those with multiple headache types.  Mean subjective patient estimate of improvement was 31.7 %.  Significant reductions were also seen in outcome measures such as pain intensity (1.34 points, p < 0.001), all monthly headache days (5.66 days, p < 0.001) and pain duration (4.54 hours, p < 0.001).  Responders showed substantial reductions in headache-related disability, affect scores and quality of life (QOL) measures.  Adverse event (AE) rates were favorable with no episodes of lead migration and only 1 minor infection reported.  The authors concluded that ONS may be a safe and efficacious treatment for highly intractable chronic migraine patients even after relatively prolonged follow up of a median of over 3 years.  Moreover, they stated that there are still concerns over the risk to benefit ratio and cost-effectiveness of ONS despite positive open-label data and a well-designed double-blind controlled trial with long-term follow-up is needed to clarify the position of neuromodulation in chronic migraine.

Cuadrado and colleagues (2017) stated that currently there is no evidence to guide the acute treatment of migraine aura.  These researchers described the effect of greater occipital nerve (GON) anesthetic block as a symptomatic treatment for long-lasting (prolonged or persistent) migraine aura.  Patients who presented with migraine aura lasting more than 2 hours were consecutively recruited during 1 year at the Headache Unit and the Emergency Department of a tertiary hospital.  All patients underwent a bilateral GON block with bupivacaine 0.5 %.  Patients were followed-up for 24 hours.  A total of 22 auras were treated in 18 patients.  Auras consisted of visual (n = 13), visual and sensory (n = 4) or sensory symptoms alone (n = 5); 11 episodes met diagnostic criteria for persistent aura (greater than 1 week) without infarction.  The response was complete without early recurrence in 11 cases (50 %), complete with recurrence in less than 24 hours in 2 cases (9.1 %), and partial with greater than or equal to 50 % improvement in 6 cases (27.3 %).  Complete responses without recurrence were more common in cases with prolonged auras lasting less than 1 week than in those with persistent auras (72.7 % versus 27.3 %; p = 0.033).  The authors concluded that GON block could be an effective symptomatic treatment for prolonged or persistent migraine aura.  Moreover, they stated that RCTs are still required to confirm these results.

In a prospective, long-term, open-label, uncontrolled observational study, Rodrigo and co-workers (2017) evaluated the long-term efficacy and tolerability of ONS for medically intractable chronic migraine.  Patients who met the International Headache Society criteria for chronic migraine, all of them having been previously treated with other therapeutic alternatives, and who met all inclusion and exclusion criteria for neuro-stimulation, received the implantation of an ONS system after a positive psychological evaluation and a positive response to a preliminary occipital nerve blockage.  The implantation was performed in 2 phases: (i) a 10 day trial with implanted occipital leads connected to an external stimulator and (ii) if more than 50 % pain relief was obtained, permanent pulse generator implantation and connection to the previously implanted leads.  After the surgery, the patients were thoroughly evaluated annually using different scales: pain visual analog scale (VAS), number of migraine attacks per month, sleep quality, functionality in social and labor activities, reduction in pain medication, patient satisfaction, tolerability, and reasons for termination.  The average follow-up time was 9.4 ± 6.1 years, and 31 patients completed a 7-year follow-up period.  A total of 37 patients were enrolled and classified according to the location and quality of their pain, accompanying symptoms, work status, and psychological effects.  Substantial pain reduction was obtained in most patients, and the VAS decreased by 4.9 ± 2.0 points.  These results remained stable over the follow-up period; 5 of the 35 permanently implanted patients with migraine attacks at baseline were free from these attacks at their last visits, whereas the pain severity decreased 3.8 ± 2.5 (according to the VAS) in the remaining patients; 7 of the 35 permanent implanted devices were definitively removed: 2 devices because of treatment inefficacy, and 5 devices because the patients were asymptomatic and considered to be cured from their pain, even with the stimulation off.  Systemic side effects were not observed.  The authors noted that they had considered that the trigemino-cervical autonomous and cervical connection may explain why ONS might relieve chronic migraine pain, but this is just a theoretical explanation which should be demonstrated in future studies.  They stated that the results achieved in this study suggested that ONS may provide long-term benefits for patients with medically intractable chronic migraine.  These outcomes were slightly better than previous reports and were maintained over the 7-year follow-up.  These researchers believed that an accurate selection of patients, realization of diagnostic occipital nerve blocks, psychological evaluations, rigorous surgical technique, and appropriate parameter programming helped them achieve these outcomes.  Moreover, they stated that controlled and larger studies are needed to confirm these results.  Drawbacks of this study included its uncontrolled and open-label design; and not all patients completed the 7-year follow-up period.

In a placebo-controlled study, Gul and colleagues (2017) evaluate the efficacy of greater occipital nerve (GON) blockade in patients with CM by using a control group.  These researchers included 44 CM patients and randomly divided the patients into 2 groups: group A (bupivacaine) and group B (placebo).  GON blockade was administered 4 times (once-weekly) with bupivacaine or saline.  After 4 weeks of treatment, patients were followed-up for 3 months, and findings were recorded once-monthly for comparing each month's values with the pre-treatment values.  The primary end-point was the difference in the frequency of headache (headache days/month); VAS pain scores were also recorded.  A total of 44 patients had completed the study; no severe adverse effects had occurred.  Group A showed a significant decrease in the frequency of headache and VAS scores at the 1st, 2nd, and 3rd months of follow-up.  Similarly, group B showed a significant decrease in the frequency of headache and VAS scores at the 1st month of follow-up, but 2nd and 3rd months of follow-up showed no significant difference.  The authors concluded that these findings suggested that GON blockade with bupivacaine was superior to placebo, had long-lasting effect than placebo, and was found to be effective for the treatment of CM.  These investigators stated that more studies are needed to better define the safety and cost-effectiveness of GON blockade in CM.

Viana and Afridi (2018) reviewed the published literature on migraine with prolonged aura (PA), specifically with regards to the phenotype and treatment options.  A recent study found that about 17 % of migraine auras are prolonged and that 26 % of patients with migraine with aura have experienced at least 1 PA.  The characteristics of PA are similar to most typical auras with the exception of a higher number of aura symptoms (in particular sensory and/or dysphasic).  There are no well-established treatments at present which target the aura component of migraine.  Other than case reports, there have been open-label studies of lamotrigine and GONs.  The only randomized, blinded, controlled trial to-date has been of nasal ketamine showing some reduction in aura severity but not duration.  A small open-labelled pilot study of amiloride was also promising.  The authors concluded that larger randomized, controlled trials are needed to establish whether any of the existing or novel compounds mentioned is significantly safe and  effective.

UpToDate reviews on “Acute treatment of migraine in adults” (Bajwa and Smith, 2018a) and “Preventive treatment of migraine in adults” (Bajwa and Smith, 2018b) do not mention occipital nerve block as a therapeutic option.

Furthermore, an UpToDate review on “Chronic migraine” (Garza and Schwedt, 2018) stated that “Occipital nerve stimulation -- There are inconsistent data from small randomized trials regarding the benefit of occipital nerve stimulation for the treatment of chronic migraine.  In the largest trial, there was no significant difference at 12 weeks for the primary endpoint, the percentage of patients that had a ≥ 50 % reduction in mean daily pain score in the active compared with the control group.  However, there were statistically significant if modest improvements with active stimulation for a number of secondary endpoints, including the percentage of patients with a ≥ 30 % reduction in mean daily pain score, and reduction in the mean number of headache days and migraine-related disability.  The findings from these reports are limited by concerns about blinding in the control (sham treatment) groups, given that active treatment causes paresthesia, and relatively high rates of complications, including lead migration in 14 to 24 %of subjects.  Further trials are needed to determine if occipital nerve stimulation is a useful therapy for chronic migraine”.

Occipital Nerve Stimulation for the Treatment of Occipital Neuralgia

Brewer and colleagues (2013) noted that occipital nerve stimulation (ONS) may provide relief for refractory headache disorders.  However, scant data exist regarding long-term ONS outcomes.  These investigators examined the long-term outcome in ONS patients with medically intractable primary headache disorders.  The methods used were retrospective review of the medical records of all (non-industry study) patients who were trialed and implanted with occipital nerve stimulator systems at the authors’ institution, followed by a phone interview.  Up to 3 attempts were made to contact each patient, and those who were contacted were given the opportunity to participate in a brief phone interview regarding their ONS experience.  Data for analysis were gleaned from both the phone interview and the patient's medical records.  A total of 29 patients underwent a trial of ONS during the 8.5-year study period; 3 patients did not go on to permanent implant, 12 could not be contacted, and 14 participated in the phone interview.  Based upon the phone interview (if the patient was contacted) or chart review, ONS was deemed successful in 5 (42 %) of the 12 migraine, 4 (80 %) of 5 cluster headache, and 5 (62.5 %) of 8 miscellaneous headache patients, and therapy was documented as long as 102 months.  In 1 of the 26 patients, success of ONS could not be determined.  Among patients deemed to have successful outcomes, headache frequency decreased by 18 %, severity by 27 %, and migraine disability score by 50 %; 58 % of patients required at least 1 lead revision.  The authors concluded that these results, although limited by their retrospective nature,  that ONS can be effective long term despite technical challenges.  The number of patients within each headache subtype was insufficient to draw conclusions regarding the differential effect of ONS.  Moreover, they stated that randomized controlled long-term studies in specific, intractable, primary headache disorders are needed.  (It is unclear how many of the 8 patients with miscellaneous headache had occipital neuralgia [ON]; and how many of the 14 who responded to the phone survey had ON; and occipital neuralgia is not listed as one of the keywords in the abstract).

Palmisani and associates (2013) performed a retrospective review of patients treated with ONS at 2 large tertiary referral centers to optimize future treatment pathways.  Patient's medical records were retrospectively reviewed, and each patient was contacted by a trained headache expert to confirm clinical diagnosis and system efficacy.  Results were compared to reported outcomes in current literature on ONS for primary headaches.  A total of 25 patients underwent a trial of ONS between January 2007 and December 2012, and 23 patients went on to have permanent implantation of ONS.  All 23 patients reached 1-year follow-up, and 14 of them (61 %) exceeded 2 years of follow-up; 17 of the 23 had refractory CM (rCM), and 3 refractory ON; 11 of the 19 rCM patients had been referred with an incorrect headache diagnosis; 9 of the rCM patients (53 %) reported 50 % or more reduction in headache pain intensity and or frequency at long term follow-up (11 to 77 months).  All 3 ON patients reported more than 50 % reduction in pain intensity and/or frequency at 28 to 31 months; 10 (43 %) subjects underwent surgical revision after an average of 11 ± 7 months from permanent implantation - in 90 % of cases due to lead problems; 7 patients attended a specifically designed, multi-disciplinary, 2-week pre-implant program and showed improved scores across all measured psychological and functional parameters independent of response to subsequent ONS.  The authors concluded that this retrospective review: (i) confirmed the long-term ONS success rate in refractory chronic headaches, consistent with previously published studies; (ii) suggested that some headaches types may respond better to ONS than others (ON versus CM); (iii) called into question the role of trial stimulation in ONS; (iv) confirmed the high rate of complications related to the equipment not originally designed for ONS; and (v) emphasized the need for specialist multi-disciplinary care in these patients.  These researchers stated that their findings were consistent with published studies that suggested ONS has a place in the management of patients with refractory chronic migraine and with refractory occipital neuralgia; however, much work needs to be done to refine patient selection and optimize the treatment.  This study has high-lighted important specific areas to focus on in the future clinical and research use of ONS.  They noted that there is a need to refine patient selection for ONS and ensure optimal medical, psychological and surgical management at all stages -- a multi-disciplinary team comprising of headache, psychology, and neuromodulation specialists is essential for this.  Such teams should be used in future randomized controlled trials with long-term follow-up to further determine the place for ONS in refractory chronic headache management and improve patient outcomes.

The authors stated that their analysis had several drawbacks.  Its design was flawed by the well-known limitations of retrospective case-series studies.  Lead/anchor technology and surgical technique have evolved so some of the problems the authors had highlighted are already being addressed.  Different measures were collected over the years, and the choice of using patients’ subjective report of headache’s intensity / frequency reduction to define long-term success was not highly robust.  Any prospective trial should now endorse the outcome measures defined by Task Force of the International Headache Society Clinical Trials Sub-Committee. Finally, these researchers couldn’t collect enough information to report and comment on medication-overuse headache.

Mekhail and co-workers (2017) noted that a recent multi-center study presented 52-week safety and efficacy results from an open-label extension of a randomized, sham-controlled trial for patients with chronic migraine (CM) undergoing ONS.  These researchers presented the data from a single-center of 20 patients enrolled at the Cleveland Clinic's Pain Management Department.  Patients were implanted with a neurostimulation system, randomized to an active or control group for 12 weeks, and received open-label treatment for an additional 40 weeks.  Outcomes collected included number of headache days, pain intensity, Migraine Disability Assessment (MIDAS), Zung Pain and Distress (PAD), direct patient reports of headache pain relief, quality of life (QOL), satisfaction, and adverse events (AEs).  Headache days per month were reduced by 8.51 (± 9.81) days (p < 0.0001).  The proportion of patients who achieved a 30 % and 50 % reduction in headache days and/or pain intensity was 60 % and 35 %, respectively.  MIDAS and Zung PAD were reduced for all patients; 15 (75 %) of the 20 patients at the site reported at least 1 AE.  A total of 20 AEs were reported from the site.  The authors concluded that these findings supported the 12-month efficacy of 20 CM patients receiving peripheral nerve stimulation of the occipital nerves in this single-center trial.  This was a small (n = 20), single-center study on the use of occipital nerve stimulation for the treatment of chronic migraine; not ON.  Moreover, these investigators stated that despite advancements on surgical techniques, AES with ONS remain prominent, thus warranting further research into both technology and implantation technique. 

Migraine Surgery

The American Headache Society guidelines (Loder et al, 2013) recommended against surgical deactivation of migraine trigger points.  It stated that “The value of this form of “migraine surgery” is still a research question.  Observational studies and a small controlled trial suggest possible benefit.  However, large multicenter, randomized controlled trials with long-term follow-up are needed to provide accurate estimates of the effectiveness and harms of surgery.  Long-term side effects are unknown but potentially a concern”.  

Sphenopalatine Nerve Block

Candido et al (2013) noted that the sphenopalatine ganglion (SPG) is located with some degree of variability near the tail or posterior aspect of the middle nasal turbinate.  The SPG has been implicated as a strategic target in the treatment of various headache and facial pain conditions, some of which are featured in this manuscript.  Interventions for blocking the SPG range from minimally to highly invasive procedures often associated with great cost and unfavorable risk profiles.  The purpose of this pilot study was to present a novel, FDA-cleared medication delivery device, the Tx360® nasal applicator, incorporating a trans-nasal needleless topical approach for SPG blocks.  This study featured the technical aspects of this new device and presented some limited clinical experience observed in a small series of head and face pain cases.  After Institutional Review Board (IRB) approval, the technical aspects of this technique were examined on 3 patients presenting with various head and face pain conditions including trigeminal neuralgia (TN), chronic migraine headache (CM), and post-herpetic neuralgia (PHN).  The subsequent response to treatment and quality of life was quantified using the following tools: the 11-point Numeric Rating Scale (NRS), Modified Brief Pain Inventory - short form (MBPI-sf), Patient Global Impression of Change (PGIC), and patient satisfaction surveys.  The Tx360® nasal applicator was used to deliver 0.5 ml of ropivacaine 0.5 % and 2 mg of dexamethasone for SPG block.  Post-procedural assessments were repeated at 15 and 30 minutes, and on days 1, 7, 14, and 21 with a final assessment at 28 days post-treatment.  All patients were followed for 1 year.  Individual patients received up to 10 SPG blocks, as clinically indicated, after the initial 28 days.  Three women, aged 43, 18, and 15, presented with a variety of headache and face pain disorders including TN, CM, and PHN.  All patients reported significant pain relief within the first 15 minutes post-treatment.  A high degree of pain relief was sustained throughout the 28 day follow-up period for 2 of the 3 study participants.  All 3 patients reported a high degree of satisfaction with this procedure.  One patient developed minimal bleeding from the nose immediately post-treatment, which resolved spontaneously in less than 5 minutes.  Longer term follow-up (up to 1 year) demonstrated that additional SPG blocks over time provided a higher degree and longer lasting pain relief.  The authors concluded that SPG block with the Tx360® is a rapid, safe, easy, and reliable technique to accurately deliver topical trans-nasal analgesics to the area of mucosa associated with the SPG.  This intervention can be delivered in as little as 10 seconds with the novice provider developing proficiency very quickly.  They stated that further investigation is certainly needed related to technique efficacy, especially studies comparing efficacy of Tx360 and standard cotton swab techniques; especially controlled, double-blind studies with a higher number of patients.

In a double-blind, parallel-arm, placebo-controlled, randomized pilot study, Cady et al (2015a) examined if repetitive SPG blocks with 0.5 % bupivacaine delivered through the Tx360 are superior in reducing pain associated with chronic migraine (CM) compared with saline.  This study used a novel intervention for acute treatment in CM.  Up to 41 subjects could be enrolled at 2 headache specialty clinics in the US.  Eligible subjects were between 18 and 80 years of age and had a history of CM defined by the second edition of the International Classification of Headache Disorders appendix definition.  They were allowed a stable dose of migraine preventive medications that was maintained throughout the study.  Following a 28-day baseline period, subjects were randomized by computer-generated lists of 2:1 to receive 0.5 % bupivacaine or saline, respectively.  The primary end-point was to compare numeric rating scale scores at pre-treatment baseline versus 15 minutes, 30 minutes, and 24 hours post-procedure for all 12 treatments.  SPG blockade was accomplished with the Tx360, which allows a small flexible soft plastic tube that is advanced below the middle turbinate just past the pterygopalatine fossa into the intra-nasal space.  A 0.3 cc of anesthetic or saline was injected into the mucosa covering the SPG.  The procedure was performed similarly in each nostril.  The active phase of the study consisted of a series of 12 SPG blocks with 0.3 cc of 0.5 % bupivacaine or saline provided 2 times per week for 6 weeks.  Subjects were re-evaluated at 1 and 6 months post-final procedure.  The final dataset included 38 subjects, 26 in the bupivacaine group and 12 in the saline group.  A repeated measures analysis of variance showed that subjects receiving treatment with bupivacaine experienced a significant reduction in the numeric rating scale scores compared with those receiving saline at baseline (M = 3.78 versus M = 3.18, p = 0.10), 15 minutes (M = 3.51 versus M = 2.53, p < 0.001), 30 minutes (M = 3.45 versus M = 2.41, p < 0.001), and 24 hours after treatment (M = 4.20 versus M = 2.85, p < 0.001), respectively.  Headache Impact Test-6 scores were statistically significantly decreased in subjects receiving treatments with bupivacaine from before treatment to the final treatment (Mdiff = -4.52, p = 0.005), whereas no significant change was seen in the saline group (Mdiff = -1.50, p = 0.13).  The authors concluded that SPG blockade with bupivacaine delivered repetitively for 6 weeks with the Tx360 device demonstrated promise as an acute treatment of headache in some subjects with CM.  Statistically significant headache relief was noted at 15 and 30 minutes and sustained at 24 hours for SPG blockade with bupivacaine versus saline.  The Tx360 device was simple to use and not associated with any significant or lasting adverse events.  They stated that further research on SPG blockade is needed.

Cady et al (2015b) performed a double-blind, parallel-arm, placebo-controlled, randomized pilot study using a novel intervention for acute treatment in CM.  A total of 41 subjects were enrolled at 2 headache specialty clinics in the USA.  Eligible subjects were between 18 and 80 years of age and had a history of CM defined by International Classification of Headache Disorders-II definition.  Subjects were allowed a stable dose of migraine preventive medications that was maintained throughout the study.  Following a 28-day baseline period, subjects were randomized by computer-generated lists 2:1 to receive 0.3 cc of 0.5 % bupivacaine or saline, respectively, delivered with the Tx360 twice a week for 6 weeks.  Secondary end-points reported in this manuscript include post-treatment measures including number of headache days and quality of life measures.  The final data set included 38 subjects: 26 in the bupivacaine group and 12 in the saline group.  The primary end-point for the study, difference in numeric pain rating scale scores, was met and reported in a previous article.  The supplemental secondary end-points reported in this manuscript did not reach statistical significance.  When looking collectively at these end-points, trends were noticed and worthy of reporting.  Subjects receiving bupivacaine reported a decrease in the number of headache days 1 month post-treatment (Mdiff = -5.71), whereas those receiving saline only saw a slight improvement (Mdiff = -1.93).  Headache Impact Test 6 scores were decreased in the bupivacaine group at 1 month (Mdiff = -5.13) and 6 months (Mdiff = -4.78) post-treatment, but only a modest reduction was seen for those receiving saline at 1 and 6 months, respectively (Mdiff = -2.08, Mdiff = -1.58).  Furthermore, subjects receiving bupivacaine reported a reduction in acute medication usage and improved quality of life measures (average pain in the previous 24 hours, mood, normal work, and general activity) up to 6 months post-treatment . The changes in these measures for the saline group were minimal.  The authors concluded that data from this exploratory pilot study suggested that there may be long-term clinical benefits with the use of repetitive SPG blockades with bupivacaine delivered with the simple to use Tx360 device.  These include a sustained reduction of headache days and improvement in several important quality of life assessments.  The SPG blockades were not associated with any significant or lasting adverse events.  They stated that further research on SPG blockade is needed.

Spinal Accessory Nerve Block

The spinal accessory nerve (9th cranial nerve) is also known as the accessory nerve.  It has 2 roots, which leave the cranium together, along with the vagus nerve, via the jugular foramen.  The fibers of the spinal root pass inferiorly and posteriorly to provide motor innervation to the superior portion of the sternocleidomastoid muscle.  The spinal accessory nerve exits the posterior border of the sternocleiodomastoid muscle in the upper 3rd of the muscle.  The nerve, in combination with the cervical plexus, provides innervation to the trapezius muscle.  Spinal accessory nerve block is useful in the diagnosis and treatment of spasm of the sternocleidomastoid or trapezius muscle.  There is no reliable data on use of the spinal accessory nerve block for headache.

UpToDate reviews on “Cervicogenic headache” (Bajwa and Watson, 2018), “Chronic migraine” (Garza and Schwedt, 2018) and “Occipital neuralgia” (Garza, 2018) do not mention spinal accessory nerve (cranial nerve IX) block as a therapeutic option.

Trigeminal Nerve Block

Ashkenazi et al (2010) stated that interventional procedures such as peripheral nerve blocks (PNBs) and trigger point injections (TPIs) have long been used in the treatment of various headache disorders.  There are, however, little data on their efficacy for the treatment of specific headache syndromes.  Moreover, there is no widely accepted agreement among headache specialists as to the optimal technique of injection, type, and doses of the local anesthetics used, and injection regimens.  The role of corticosteroids in this setting is also debated.  These researchers performed a PubMed search of the literature to find studies on PNBs and TPIs for headache treatment.  They classified the abstracted studies based on the procedure performed and the treated condition.  They found few controlled studies on the efficacy of PNBs for headaches, and virtually none on the use of TPIs for this indication.  The most widely examined procedure in this setting was greater occipital nerve block, with the majority of studies being small and non-controlled.  The techniques, as well as the type and doses of local anesthetics used for nerve blockade, varied greatly among studies.  The specific conditions treated also varied, and included both primary (e.g., migraine, cluster headache) and secondary (e.g., cervicogenic, post-traumatic) headache disorders.  Trigeminal (e.g., supra-orbital) nerve blocks were used in few studies.  Results were generally positive, but should be taken with reservation given the methodological limitations of the available studies.  The procedures were generally well-tolerated.  The authors concluded that there is a need to perform more rigorous clinical trials to clarify the role of PNBs and TPIs in the management of various headache disorders, and to aim at standardizing the techniques used for the various procedures in this setting.

The Institute for Clinical Systems Improvement’s clinical guideline on “Diagnosis and treatment of headache” (Beithon et al, 2013) did not mention trigeminal nerve block as a therapeutic option.

Giblin et al (2014) described a case of cervicogenic headache with associated autonomic features and pain in a trigeminal distribution, all of which responded to 3rd occipital nerve radiofrequency ablation.  This study discussed the case of a 38-year old woman with history of migraines and motor vehicle accident.  Right third occipital nerve diagnostic blocks and radiofrequency lesioning were carried out.  Outcome measures included pain reduction; physical findings, including periorbital and mandibular facial swelling, tearing, conjunctival injection, and allodynia; and use of opioid and non-opioid pain medicines.  The patient had complete relief of her pain and autonomic symptoms, and was able to stop all pain medications following a dedicated third occipital nerve lesioning.  The authors concluded that this case illustrated the diagnostic and therapeutic complexity of cervicogenic headache and the overlap with other headache types, including trigeminal autonomic cephalgias and migraine.  It represented a unique proof of principle in that not only trigeminal nerve pain but also presumed neurogenic inflammation can be relieved by blockade of cervical nociceptive inputs.  They stated that further investigation into shared mechanisms of headache pathogenesis is warranted.

Furthermore, UpToDate reviews on Cervicogenic headache” (Bajwa and Watson, 2018), “Chronic migraine” (Garza and Schwedt, 2018) and “Occipital neuralgia” (Garza, 2018) do not mention trigeminal nerve block as a therapeutic option.

Subcutaneous Peripheral Nerve Field Stimulation for the Treatment of Nummular Headache

Bunger and colleagues (2018) noted that subcutaneous peripheral nerve field stimulation (sPNFS) is an established procedure for the treatment of chronic localized neuropathic pain of peripheral origin.  Nummular headache (also known as coin-shaped cephalagia) is defined as a mild-to-moderate, pressure-like pain that is felt exclusively in a rounded or elliptical area typically 2 to 6 cm in diameter.  While the pathogenesis of nummular headache remains unclear, its treatment primarily focuses on conservative methods with limited prospects of success.  The role of sPNFS in the treatment of nummular headache has not been investigated as yet.  These researchers examined if sPNFS can be a therapeutic option in the management of nummular headache.  They reported that of sPNFS showed a positive effect in the treatment of nummular headache.  The authors concluded that sPNFS stimulated free subcutaneous nerves and transmitted a pleasant form of paresthesia in the area of pain.  If regular conservative therapy has already been exhausted, then sPNFS might be an effective new option in the treatment of nummular headache.  These investigators stated that sPNFS is a minimally invasive and low-risk procedure.  However, the high treatment cost and restrictions regarding fitness to undergo MRI are points of criticism.  Moreover, they stated that further studies are needed to define its potential and role in the treatment of nummular headache.

The above policy is based on the following references: