Description:
Occipital nerve stimulation delivers a small electrical charge to the occipital nerve intended to prevent migraines and other headaches in patients who have not responded to medications. The device consists of a subcutaneously implanted pulse generator (in the chest wall or abdomen) attached to extension leads that are tunneled to join electrodes placed across 1 or both occipital nerves at the base of the skull. Continuous or intermittent stimulation may be used.

Background
HEADACHE
There are 4 types of headache: vascular, muscle contraction (tension), traction, and inflammatory. Primary (not the result of another condition) chronic headache is defined as headache occurring more than 15 days of the month for at least 3 consecutive months. An estimated 45 million Americans experience chronic headaches. For at least half of these people, the problem is severe and sometimes disabling. Herein, we only discuss types of vascular headache, including migraine, hemicrania continua, and cluster.

Migraine
Migraine is the most common type of vascular headache. Migraine headaches are usually characterized by severe pain on one or both sides of the head, an upset stomach, and, at times, disturbed vision. One-year prevalence of migraine ranges from 6% to 15% in adult men and from 14% to 35% in adult women. Migraine headaches may last a day or more, and they can strike as often as several times a week or as rarely as once every few years.

Treatment
Drug therapy for migraine is often combined with biofeedback and relaxation training. Sumatriptan and other triptans are commonly used for relief of symptoms. Drugs used to prevent migraine include amitriptyline, propranolol and other β-blockers; topiramate and other antiepileptic drugs; and verapamil.

Hemicrania Continua
Hemicrania continua causes moderate and occasionally severe pain on only one side of the head. At least one of the following symptoms must also occur: conjunctival injection and/or lacrimation, nasal congestion and/or rhinorrhea, or ptosis, and/or miosis. Headache occurs daily and is continuous with no pain-free periods. Hemicrania continua occurs mainly in women, and its true prevalence is not known. 

Treatment
Indomethacin usually provides rapid relief of symptoms. Other nonsteroidal anti-inflammatory drugs, including ibuprofen, celecoxib, and naproxen, can provide some relief of symptoms. Amitriptyline and other tricyclic antidepressants are effective in some patients.

Cluster Headache
Cluster headache occurs in cyclical patterns or clusters of severe or very severe unilateral orbital or supraorbital and/or temporal pain. The headache is accompanied by at least one of the following autonomic symptoms: ptosis, conjunctival injection, lacrimation, rhinorrhea, and, less commonly, facial blushing, swelling, or sweating. Bouts of 1 headache every other day up to 8 attacks per day may last from weeks to months, usually followed by remission periods when the headache attacks stop completely. The pattern varies by person, but most people have 1 or 2 cluster periods a year. During remission, no headaches occur for months and sometimes even years. The intense pain is caused by the dilation of blood vessels, which creates pressure on the trigeminal nerve. While this process is the immediate cause of the pain, the etiology is not fully understood. It is more common in men than in women. One-year prevalence is estimated to be 0.5 to 1.0 in 1,000.

Treatment
Management of cluster headache consists of abortive and preventive treatment. Abortive treatments include subcutaneous injection of sumatriptan, topical anesthetics sprayed into the nasal cavity, and strong coffee. Some patients respond to rapidly inhaled pure oxygen. A variety of other pharmacologic and behavioral methods of aborting and preventing attacks have been reported with wide variation in patient response.

Peripheral Nerve Stimulators
Implanted peripheral nerve stimulators have been used to treat refractory pain for many years but have only recently been proposed to manage craniofacial pain. Occipital, supraorbital, and infraorbital stimulation have been reported in the literature.

Peripheral Nerve Stimulators
Peripheral (occipital and supraorbital) and cranial (trigeminal) nerve stimulation using an implantable device has been explored as an approach to treat numerous chronic pain conditions. The surgical procedure involves the surgical implantation of a small electrical device (a wire-like electrode) adjacent to the selected nerve(s). The electrode delivers rapid electrical pulses near the selected nerve, regardless of the specific nerve targeted. During the trial stimulation, the electrode is connected to an external device, and if the trial is successful, a small generator is implanted into the patient’s body. An electrical current is delivered from the generator to the nerve or nerves using one or several electrodes. The subject is able to control the intensity of the stimulation by turning the device on and off and adjusting stimulation parameters as needed.

Use of an implantable nerve stimulation device may be referred to as occipital, supraorbital or trigeminal nerve stimulation, depending upon the nerves that are being targeted for stimulation.

The implantation of an occipital, supraorbital or trigeminal nerve stimulation device may cause some complications.

Lead migration, power depletion in the pulse generator, and the possibility of infection are the most frequent problems requiring removal and replacement of the implantable nerve stimulation device.

Occipital Nerve Stimulation
Occipital nerve stimulation (ONS) delivers a small electrical charge to the occipital nerve in an attempt to prevent migraines and other headaches in patients who have not responded to medications. The device consists of a subcutaneously implanted pulse generator (in the chest wall or abdomen) attached to extension leads that are tunneled to join electrodes placed across one or both occipital nerves at the base of the skull. Continuous or intermittent stimulation may be used.

Supraorbital Nerve Stimulation
Supraorbital nerve stimulation includes the neurostimulation of both occipital and supraorbital nerves. Researchers have been exploring the utilization of supraorbital nerve stimulation as a treatment for chronic migraine. Participants were evaluated with the migraine disability assessment scale (MIDAS) and the Beck Depression Inventory (BDI) both preoperatively and postoperatively.

Trigeminal Nerve Stimulation for Trigeminal Neuralgia
Trigeminal neuralgia (TN) is a chronic pain condition that affects the trigeminal (5th cranial) nerve, one of the most widely distributed nerves in the head. Treatment options may include pharmacologic therapy, surgical interventions (including but not limited to rhizotomy), and other complementary approaches.

Treatment
Trigeminal nerve stimulation has been explored as a treatment for trigeminal neuralgia. Similar to occipital nerve stimulation and supraorbital nerve stimulation, trigeminal nerve stimulation involves the implantation of a pulse generator and electrodes to deliver mild electrical signals to branches of the trigeminal nerve in order to provide neuromodulation of pain. Implantation of the electrodes is considered a minimally invasive procedure. Postoperative complications may include nerve damage, pain, infection, electrode migration, mechanical failure (e.g., disconnection of hardware and failure to provide adequate pain relief) and cosmetic concerns.

Regulatory Status 

To date, the U.S. Food and Drug Administration (FDA) has not cleared or approved any occipital nerve stimulation device for treatment of headache. In 1999, the Synergy^™ IPG device (Medtronic), an implantable pulse generator, was approved by FDA through the premarket approval process for management of chronic, intractable pain of the trunk or limbs, and off-label use for headache is described in the literature. The Genesis^™ neuromodulation system (St. Jude Medical) was approved by FDA for spinal cord stimulation and the Eon^™ stimulator has received CE mark approval in Europe for the treatment of chronic migraines.

Related Policies
70125 Spinal Cord Stimulation

Policy:
Occipital nerve stimulation is investigational/unproven therefore is considered NOT MEDICALLY NECESSARY for all indications.

Infraorbital/Supraorbital nerve stimulation is investigational/unproven therefore is considered NOT MEDICALLY NECESSARY for all indications.

Trigeminal nerve stimulation is investigational/unproven therefore is considered NOT MEDICALLY NECESSARY for all indications.  

Implantable peripheral nerve stimultor (StimRouter and ReActiv8) are considered investigational and/or unproven and therefore NOT MEDICALLY NECESSARY for all clinical indications.  

Policy Guidelines
Coding
See the Codes table for details.

Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all devices, drugs or biologics approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational and, thus, these devices may be assessed only on the basis of their medical necessity.

Rationale 
Review of Evidence Regarding StimRouter
Systematic Reviews
There were no systematic reviews identified.  

Case Series
The majority of the literature related to implantable peripheral nerve stimulation for various conditions (e.g., treatment of hemiplegic shoulder pain; peripheral neuropathic pain; intercostal neuralgia; back pain; neck pain; occipital neuralgia; postherpetic neuralgia; and trigeminal neuralgia/trigeminal neuropathic pain) is case series. While case series are appropriate for introducing novel interventions, they have inherent limitations. Results may be generalized, there are no controls, outcomes are not blinded, assessor bias cannot be ruled out, no comparative information to alternative treatments and no long- term follow-up. These case series may show promising results, however, to be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative treatment(s) at a comparable intensity with long term follow-up to verify safety and efficacy. 

Randomized Controlled Trials 
In 2012, Silberstein et al. published a randomized, controlled, double-blinded multicenter study on the safety and efficacy of peripheral nerve stimulation (PNS) of the 
occipital nerves for the management of chronic migraine in 157 patients. The patients were randomized to active treatment (n = 105) or sham treatment (n = 52). The primary 
endpoint was a difference in the percentage of responders (defined as patients that achieved a ≥ 50% reduction in mean daily visual analog scale scores) in each group at 12 
weeks. There was not a significant difference in the percentage of responders in the Active compared with the Control group (95% lower confidence bound (LCB) of -0.06; p 
= 0.55). However, there was a significant difference in the percentage of patients that achieved a 30% reduction (p = 0.01). Importantly, compared with sham-treated patients, 
there were also significant differences in reduction of number of headache days (Active Group = 6.1, baseline = 22.4; Control Group = 3.0, baseline = 20.1; p = 0.008), migraine related disability (p = 0.001) and direct reports of pain relief (p = 0.001). The most common adverse event was persistent implant site pain. The authors concluded, although this study failed to meet its primary endpoint, this is the first large scale study of (PNS) of the occipital nerves in chronic migraine patients that showed significant reductions in pain, headache days, and migraine-related disability. Additional controlled studies are warranted in this highly disabled patient population with a large unmet medical need.

In 2016, Deer et al. published a prospective, multicenter, randomized, double-blinded, partial crossover study to assess the safety and efficacy of the StimRouter neuromodulation system in the treatment of 94 patients with chronic pain of peripheral nerve origin. After IRB approval, patients were enrolled, implanted, and then followed for three months to assess efficacy and one year for safety based on Food and Drug Administration guidance. The patients were randomized to the treatment StimRouter group (45) or the control group (n = 49). The primary efficacy endpoint, three months after randomization to treatment, demonstrated that patients receiving active stimulation achieved a statistically significantly higher response rate of 38% vs. the 10% rate found in the Control group (p = 0.0048). Improvement in pain was statistically significant 
between the randomized groups, with the Treatment group achieving a mean pain reduction of 27.2% from Baseline to Month 3 compared to a 2.3% reduction in the Control group (p < 0.0001). During the partial crossover period, patients again demonstrated statistically significant improvement in pain relief with active stimulation compared to baseline. Further, the treatment group had significantly better improvement than the control group in secondary measures including but not limited to quality of life and satisfaction. Safety, assessed throughout the trial and with follow-up to one year, demonstrated no serious adverse events related to the device. All device-related adverse events were minor and self-limiting. However, the results need confirmation in additional randomized controlled trials (RCTs) with longer follow-up to draw conclusions. Studies should also compare StimRouter with other peripheral nerve stimulation systems such as spinal cord stimulation and alternative treatments.

Ongoing Trials
A prospective, multi-center, single-arm study that will include 50 participants to assess StimRouter’s effectiveness for treating severe intractable chronic shoulder pain 
subsequent to stroke. The primary endpoint will be a clinically relevant pain reduction (30%) in pain score at 3 months after initiating stimulation in at least 50% of patients with no increase in pain medication. Expected completion October 2020 (NCT03093935). This study will not provide the data needed to confirm efficacy and safety because it has no control group, and chronic pain waxes and wanes over time, pain is a subjective measure, and single-arm study design will have a high risk of bias so that results cannot be reliably attributed to the ntervention. Accessed ClinicalTrials.gov on October 3, 2021, and this clinical trial was terminated due to lack of subject participation.

A prospective open label long term multicenter registry to evaluate the long-term effectiveness, safety, and tolerability of the StimRouter Neuromodulation System, along with evaluating the technical performance of StimRouter, surgical outcomes, health related quality of life, concomitant medical use and subject’s impression of improvement. The primary endpoints are change in numeric pain rating scale, number of subjects with adverse events, vital signs including height, weight, heart rate and blood pressure, physical and neurological exams through 60-months post-implant. Expected completion is April 2028 (NCT03913689).

Summary of Evidence 
Based on review of the peer-reviewed medical literature regarding StimeRouter the evidence is limited to a small number of randomized controlled trials and case series that suggests implantable peripheral nerve stimulation is safe and works as intended to treat chronic pain of peripheral nerve origin. However, results need confirmation in additional randomized controlled trials (RCTs) with longer follow-up to draw conclusions on safety and efficacy. Further studies should also compare implantable peripheral nerve stimulation with other neurostimulation therapy such as spinal cord stimulation and alternative treatments. Currently there are no evidence based clinical practice guidelines that recommend the use of implantable peripheral nerve stimulation for the treatment of chronic pain of peripheral nerve origin. The evidence is insufficient to determine the effects of this technology on net health outcomes.

Review of Evidence Regarding ReActiv8 
Hayes Evolving Evidence Review completed May 2022 regarding ReActiv8 implantable neurostimulation system for chronic low back pain includes randomized controlled trials (RCTs), which may have shown some promise regarding improvement in pain, disability and quality of life (QOL). However, no studies compared ReActive8 with an active comparator, and several serious adverse events were reported. Mild and moderate adverse events were common, some of which required revision surgery and reimplantation. There were no professional society guidelines found addressing the use of ReActive8 in the treatment of chronic low back pain (CLBP). No systematic reviews were found. There are ongoing clinical trials and should be monitored for additional follow-up data.

The ReActiv8 Implantable Peripheral Neurostimulation System includes an implantable pulse generator (IPG), 2 stimulation leads, a magnet, and a wireless remote. The IPG delivers electrical stimulation pulses to certain nerves responsible for activating the lumbar multifudus muscle, the key muscles responsible for stabilizing the lower back. It is intended to help with the management of chronic low back pain (LBP) associated with the muscular weakness of the lumbar multifidus muscle in patients who have failed therapy including pain medications and physical therapy and are not candidates for spine surgery. Before implanting the device, multifudus muscle atrophy and weakness must be shown using magnetic resonance imaging (MRI) or during a physical examination using the prone instability test.

In 2021, Mitchell et al. reported the 4-year outcomes of the ReActiv8-A Trial. Eligible patients had disabling chronic low back pain (CLBP), no indications for spine surgery or spinal cord stimulation (SCS) and failed conventional management including at least physical therapy (PT) and medications for low back pain (LBP). Fourteen days post-implantation, stimulation parameters were programmed to elicit strong, smooth contractions of the multifidus, and subjects were given instructions to activate the device for 30-min stimulation-sessions twice-daily. Annual follow-up through 4 years included collection of NRS, ODI, and European QOL Score on 5 Dimensions (EQ-5D). At baseline (n = 53) (mean ± SD) age was 44 ± 10 years; duration of back pain was 14 ± 11 years, NRS was 6.8 ± 0.8, ODI 44.9 ± 10.1, and EQ-5D 0.434 ± 0.185. Mean improvements from baseline were statistically significant (p < 0.001) and clinically meaningful for all follow-ups. Patients completing year 4 follow-up, reported mean (± standard error of the mean) NRS: 3.2 ± 0.4, ODI: 23.0 ± 3.2, and EQ-5D: 0.721 ± 0.035. Moreover, 73% of subjects had a clinically meaningful improvement of greater than or equal to 2 points on NRS, 76% of greater than or equal to 10 points on ODI, and 62.5% had a clinically meaningful improvement in both NRS and ODI and 97% were (very) satisfied with treatment. The authors concluded that in patients with disabling intractable CLBP who receive long-term restorative neurostimulation, treatment satisfaction remains high; pain and disability in the 4‐year completed case cohort were on average 53% and 50% lower than baseline, respectively, suggesting that the effects were durable over the long-term. Moreover, these researchers stated that the longitudinal analysis presented was not without limitations. After 4 years, 19/53 (35.9%) patients were missing data for various reasons. Furthermore, the relatively high lead revision rate that contributed to early attrition may also have impacted reported outcomes.

In 2021, Galligan et al. performed a randomized, double-blind, sham-controlled trial at 26 multi-disciplinary centers to determine the safety and effectiveness of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms. A total of 204 eligible subjects with refractory mechanical CLBP and a positive prone instability test indicating impaired multifidus control were implanted and randomized to therapeutic (n = 102) or low-level sham (n = 102) stimulation of the medial branch of the dorsal ramus nerve (multifidus nerve supply) for 30 mins twice daily. The primary endpoint was the comparison of responder proportions (greater than or equal to 30% relief on the LBP-VAS without analgesics increase) at 120 days. After the primary endpoint assessment, subjects in the sham-control group switched to therapeutic stimulation and the combined cohort was evaluated through 1 year for long-term outcomes and AEs. The primary endpoint was inconclusive in terms of treatment superiority (57.1% versus 46.6%; difference: 10.4%; 95% confidence interval [CI]: -3.3% to 24.1%, p = 0.138). Pre-specified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related AEs (3.9%) compared favorably with other neuromodulation therapies for chronic pain. The authors concluded that this double-blind, randomized, sham-controlled trial provided important insights and design considerations for future neuromodulation trials. Although the primary endpoint was inconclusive, overall data from the blinded phase of this trial were consistent with a clinically meaningful benefit at 120 days. After unblinding and the switch from sham to therapeutic stimulation in the sham-control group, improvements increased over time out to 1 year in the combined cohort. The incidence of serious procedure- or device-related AEs compared favorably with rates published for other neuromodulation therapies for chronic pain. Follow-up of subjects in this trial will continue for a total of 5 years, providing additional insights into the long-term benefits, risks, and reliability of this device. There were several drawbacks that need to be addressed when interpreting the findings in this study. First, at the time of trial design, the size and duration of the sham response to this type of treatment in subjects with CLBP was unknown. The statistical design assumptions, derived from a literature review for available CLBP treatments, under-estimated the response to a surgically implanted active sham device. Although the LBP-VAS trajectory suggested that the sham effect may be reversing at 120 days, due to the pre-specified switch of the sham-control group to therapeutic stimulation, these investigators were unable to confirm this longer term. Second, although previous studies had shown that observed improvements with this rehabilitative treatment accrue over time, endpoint timing was set to 120 days for practical and ethical reasons, and the fixed 30% threshold for pain relief reflected the expected improvement at 120 days rather than the fully accrued long-term treatment effect. Finally, although sham stimulation parameters were set to low amplitude and frequency values, a potential therapeutic effect could not be ruled out and this might have diminished the magnitude of the group differences in the outcome measures.

Galligan et al. (2021) The ReActiv8-B randomized, active-sham-controlled trial provided safety and effectiveness evidence for this device, and all subjects received therapeutic stimulation from 4 months onward. These authors examined the 2-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. Open[1]label follow-up of 204 subjects implanted with a restorative neurostimulation system (ReActiv8) was carried out. Pain intensity (VAS), disability (ODI), QOL (EQ-5D-5L), and opioid intake were examined at baseline, 6 months, 1 year, and 2 years after activation. At 2 years (n = 156), the proportion of subjects with greater than or equal to 50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS less than or equal to 2.5 cm); 61% had a reduction in ODI of greater than or equal to 20 points, 76% had improvements of greater than or equal to 50% in VAS and/or greater than or equal to 20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 87% of subjects had continued device use during the 2nd year for a median of 43% of the maximum duration, and 60% (34 of 57) had voluntarily discontinued (39%) or reduced (21%) opioid intake. The authors concluded that at 2 years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provided evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction. However, the authors stated that the main drawback of this study was the absence of a long-term comparator because of therapy activation in the sham-control group after conclusion of the blinded phase at 4 months. Furthermore, studies with long follow-up durations will inherently have to account for missing data, especially those for chronic pain conditions. Indiscriminate use of last observation carried forward has been criticized as a source of systematic bias in chronic pain trials, and more appropriate methods have been recommended.

Furthermore, there is an ongoing clinical trial on “ReActiv8 Implantable Neurostimulation System for Chronic Low Back Pain (ReActiv8-B)” with an estimate study completion date of December 2023.

In 2021, Provenzano et al. stated that neurostimulation techniques for the treatment of chronic LBP have been rapidly evolving; however, questions remain as to which modalities provide the most effective and durable treatment for intractable axial symptoms. Modalities of spinal cord stimulation (SCS), such as traditional low-frequency paresthesia based, high-density or high dose (HD), burst, 10-kHz high-frequency therapy, closed-loop, and differential target multiplexed, have been limitedly studied to determine their efficacy for the treatment of axial LBP. Furthermore, stimulation methods that target regions other than the spinal cord, such as medial branch nerve stimulation of the multifidus muscles and the dorsal root ganglion (DRG) may also be viable therapeutic options. The authors concluded that the minimal invasiveness of neurostimulation remains a compelling reason for patients to seek this therapeutic option for the treatment of axial LBP. Invasive surgical methods (e.g., fusion) that alter the anatomy of the spine with considerable rates of failure and high AEs rates are often considered before neurostimulation. These researchers stated that if neurostimulation is shown to demonstrate long-term effectiveness in appropriately designed RCTs with low complication and explant rates, then neurostimulation therapies may move up in the treatment algorithm for chronic axial LBP and refractory nonsurgical LBP.

In 2018, Deckers et al. in a prospective, single-arm, multi-center clinical trial, examined restorative neurostimulation eliciting episodic contraction of the lumbar multifidus for treatment of chronic mechanical LBP (CMLBP) in patients who have failed conventional therapy and are not candidates for surgery or spinal cord stimulation (SCS). A total of 53 subjects were implanted with a neurostimulator (ReActiv8, Mainstay Medical Limited, Dublin, Ireland). Leads were positioned bilaterally with electrodes close to the medial branch of the L2 dorsal ramus nerve. The primary outcome measure was LBP evaluated on a 10-point numerical rating scale (NRS). Responders were defined as subjects with an improvement of at least the Minimal Clinically Important Difference (MCID) of greater than or equal to 2-point in LBP NRS without a clinically meaningful increase in LBP medications at 90 days. Secondary outcome measures included Oswestry Disability Index (ODI) and QOL (EQ-5D). For 53 subjects with an average duration of CLBP of 14 
years and average NRS of 7 and for whom no other therapies had provided satisfactory pain relief, the responder rate was 58%. The percentage of subjects at 90 days, 6 
months, and 1 year with greater than or equal to MCID improvement in single day NRS was 63%, 61%, and 57%, respectively. Percentage of subjects with greater than or 
equal to MCID improvement in ODI was 52%, 57%, and 60% while those with greater than or equal to MCID improvement in EQ-5D was 88%, 82%, and 81%. There were 
no unanticipated AEs or serious AEs related to the device, procedure, or therapy. The initial surgical approach led to a risk of lead fracture, which was mitigated by a 
modification to the surgical approach. The authors concluded that electrical stimulation to elicit episodic lumbar multifidus contraction is a new therapeutic option for CMLBP; 
results demonstrated clinically important, statistically significant, and lasting improvement in pain, disability, and QOL. However, this study had several drawbacks. 
First, it did not include a control arm. Second, the primary outcome measure in this study was improvement in pain evaluated with the NRS; however, evaluating changes in 
multiple outcome measures may be more clinically relevant (e.g., many trials of spine surgery for LBP used a composite outcome measure including assessment of 
disability). Third, lead issues that resulted in loss of stimulation for a period of time may have negatively impacted the outcomes in the affected subjects. Fourth, outcome data to 1 year were presented. Subjects in this study will continue to be evaluated annually through 5 years as part of a post-market clinical follow‐up study, which will provide 
information on longer term safety and efficacy. Finally, the data from this trial have not been analyzed to examine patient parameters that could be predictive of outcomes, and 
further research is needed to more clearly identify the best candidates for this therapy.

Summary of Evidence 
Based on review of the peer reviewed medical literature regarding ReActive8 the evidence is limited to randomized controlled trials (RCTs) and no systematic reviews. 
While randomized controlled trials may have shown promise regarding improvement in pain, disability, and quality of life (QOL), there were no studies that compared ReActive8 with an active comparator and there were several serious adverse events reported to include mild and moderate adverse events which were common some of which required a need for revision surgery and reimplantation. There are currently no professional society guidelines found addressing the use of ReActive8 in the treatment of chronic low back pain (CLBP). Further comparative studies with longer follow-up are needed, there is an ongoing clinical trial on “ReActiv8 Implantable Neurostimulation System for Chronic Low Back Pain (ReActiv8-B)” with an estimate study completion date of December 2023. Currently, there is insufficient evidence to support the use of the Reactiv8 device for the treatment of chronic LBP.

Practice Guidelines and Position Statements
Currently there are no evidence based clinical practice guidelines that recommend the use of implanted peripheral nerve stimulation (StimRouter or ReActiv8) for the treatment of pain of peripheral nerve origin and the treatment of chronic low back pain. 

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in Supplemental Information if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

Congress of Neurological Surgeons
In 2015, the Congress of Neurological Surgeons released an evidence-based guideline that stated, “the use of occipital nerve stimulators is a treatment option for patients with medically refractory occipital neuralgia.”¹⁵ The guideline was jointly funded by Congress of Neurological Surgeons and the Joint Section on Pain of the American Association of Neurological Surgeons/Congress of Neurological Surgeon. The statement had a level III recommendation based on a systematic review of literature (see Rationale section) that only identified case series.

National Institute for Health and Care Excellence
In 2013, the National Institute for Health and Care Excellence issued a guidance informed by a systematic review noting that the evidence on occipital nerve stimulation for intractable chronic migraine showed “some efficacy in the short term but very little evidence about long‑term outcomes. With regard to safety, there is a risk of complications, needing further surgery.”¹⁶

U.S. Preventive Services Task Force Recommendations
Not applicable

Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 1. 

Table 1. Summary of Key Trials

NCT: national clinical trial.

References:   

1. Chen YF, Bramley G, Unwin G, et al. Occipital nerve stimulation for chronic migraine — a systematic review and meta-analysis. PLoS One. 2015; 10(3): e0116786. PMID 25793740
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3. Saper JR, Dodick DW, Silberstein SD, et al. Occipital nerve stimulation for the treatment of intractable chronic migraine headache: ONSTIM feasibility study. Cephalalgia. Feb 2011; 31(3): 271-85. PMID 20861241
4. Silberstein SD, Dodick DW, Saper J, et al. Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: results from a randomized, multicenter, double-blinded, controlled study. Cephalalgia. Dec 2012; 32(16): 1165-79. PMID 23034698
5. Dodick DW, Silberstein SD, Reed KL, et al. Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: long-term results from a randomized, multicenter, double-blinded, controlled study. Cephalalgia. Apr 2015; 35(4): 344-58. PMID 25078718
6. Burns B, Watkins L, Goadsby PJ. Treatment of hemicrania continua by occipital nerve stimulation with a bion device: long-term follow-up of a crossover study. Lancet Neurol. Nov 2008; 7(11): 1001-12. PMID 18845482
7. Burns B, Watkins L, Goadsby PJ. Treatment of intractable chronic cluster headache by occipital nerve stimulation in 14 patients. Neurology. Jan 27 2009; 72(4): 341-5. PMID 19171831
8. Magis D, Gerardy PY, Remacle JM, et al. Sustained effectiveness of occipital nerve stimulation in drug-resistant chronic cluster headache. Headache. Sep 2011; 51(8): 1191-201. PMID 21848953
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12. Miller S, Watkins L, Matharu M. Treatment of intractable chronic cluster headache by occipital nerve stimulation: a cohort of 51 patients. Eur J Neurol. Feb 2017; 24(2): 381-390. PMID 27995704
13. Leplus A, Fontaine D, Donnet A, et al. Long-Term Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache. Neurosurgery. Jan 13 2021; 88(2): 375-383. PMID 32985662
14. Vadivelu S, Bolognese P, Milhorat TH, et al. Occipital nerve stimulation for refractory headache in the Chiari malformation population. Neurosurgery. Jun 2012; 70(6): 1430-6; discussion 1436-7. PMID 22418582
15. Sweet JA, Mitchell LS, Narouze S, et al. Occipital Nerve Stimulation for the Treatment of Patients With Medically Refractory Occipital Neuralgia: Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline. Neurosurgery. Sep 2015; 77(3): 332-41. PMID 26125672
16. National Institute for Health and Care Excellence. Occipital nerve stimulation for intractable chronic migraine [IPG452]. 2013; https://www.nice.org.uk/guidance/ipg452. Accessed March 10, 2021.
17. ECRI. Product Brief StimRouter Neuromodulation System (Bioness, Inc.) for Treating Peripheral Nerve Pain. Published April 2018.
18. Centers for Medicare and Medicaid Services. National Coverage Determination (NCD) for Electrical Nerve Stimulators (160.7).
19. Department of Health and Human Services Food and Drug Administration. StimQ Peripheral Nerve Stimulator (PNS) System
20. Stimwave. StimQ PNS System.
21. Department of Health and Human Services Food and Drug Administration. StimRouter Neuromodulation System
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Coding Section 

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.  

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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