Latest Review Date: May 2024

Category: Surgery                                                                 

POLICY:

Responsive Neurostimulation (e.g., NeuroPace RNS System) may be considered medically necessary for individuals with focal epilepsy who meet ALL of the following criteria:

• Are 18 years or older;
• Have a diagnosis of focal seizures with one or two well-localized seizure foci identified;
• Have an average of 3 or more disabling seizures (e.g., motor focal seizures, complex focal seizures, or secondary generalized seizures) per month over the prior 3 months;
• Are refractory to medical therapy (have failed two or more appropriate antiepileptic medications at therapeutic doses);
• Are not candidates for focal resective epilepsy surgery (e.g., have an epileptic focus near eloquent cerebral cortex; have bilateral temporal epilepsy);
• Do not have contraindications for RNS placement. *

Responsive Neurostimulation is considered investigational for all other indications.

POLICY GUIDELINES:

*Contraindications for RNS placement include three or more specific seizure foci, presence of primary generalized epilepsy, or presence of a rapidly progressive neurologic disorder.

DESCRIPTION OF PROCEDURE OR SERVICE:

Responsive neurostimulation (RNS) for the treatment of epilepsy involves the use of one or more implantable electric leads that serve as both a seizure detection and neurostimulation function. The device is programmed using a proprietary algorithm to recognize seizure patterns from electrocorticography output and to deliver electrical stimulation with the goal of terminating a seizure. One device, the NeuroPace RNS System, has U.S. Food and Drug Administration (FDA) approval for the treatment of refractory focal (formerly partial) epilepsy.

Epilepsy Treatment

Medical Therapy for Focal Seizures

Focal seizures (previously referred to as partial seizures) arise from a discrete area of the brain and can cause a range of symptoms, depending on the seizure type and the brain area involved.

Standard therapy for seizures, including focal seizures, includes treatment with one or more of various antiepileptic drugs (AEDs) which include newer AEDs, such as oxcarbazepine, lamotrigine, topiramate, gabapentin, pregabalin, levetiracetam, tiagabine, and zonisamide.  Currently, response to AEDs is less than ideal: one systematic review of comparing newer AEDs for refractory focal epilepsy reported an overall average responder rate in the treatment groups of 34.8%.  As a result, a substantial numbers of individuals do not achieve good seizure control with medications alone.

Surgical Therapy for Seizures

When a discrete seizure focus can be identified, seizure control may be achieved through resection of the seizure focus (epilepsy surgery). For temporal lobe epilepsy, a RCT has demonstrated that surgery for epilepsy was superior to prolonged medical therapy in reducing seizures associated with impaired awareness and in improving quality of life.  Surgery for refractory focal epilepsy (excluding simple focal seizures) is associated with five-year freedom from seizures of 52%, with 28% of seizure-free individuals able to discontinue AEDs. Selection of appropriate individuals for epilepsy surgery is important, because those with nonlesional extratemporal lobe epilepsy have worse outcomes after surgery than those with nonlesional temporal lobe epilepsy. Some individuals are not candidates for epilepsy surgery if the seizure focus is located in an eloquent area of the brain or other region that cannot be removed without risk of significant neurological deficit.

Neurostimulation for Neurologic Disorders

Electrical stimulation at one of several locations in the brain has been used as therapy for epilepsy, either as an adjunct to or as an alternative to medical or surgical therapy. Vagus nerve stimulation (VNS) has been widely used for refractory epilepsy, following FDA approval of a VNS device in 1997 and 2 RCTs evaluating VNS in epilepsy.  Although the mechanism of action for VNS’s is are not fully understood, VNS is thought reduce seizure activity through activation of vagal visceral afferents with diffuse central nervous system projections, leading to a widespread effect on neuronal excitability.

Stimulation of other locations in the neuroaxis has been studied for a variety of neurologic disorders. Electrical stimulation at deep brain nuclei (deep brain stimulation [DBS]) involves the use of chronic, continuous stimulation of a target. It has been most widely used in the treatment of Parkinson disease and other movement disorders, but has also been investigated for treating epilepsy. DBS of the anterior thalamic nuclei was studied in a RCT, the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) trial, but DBS is not currently approved by FDA for stimulation of the anterior thalamic nucleus. Stimulation of the cerebellar and hippocampal regions and the subthalamic, caudate, and centromedian nuclei have also been evaluated for the treatment of epilepsy.

Responsive Neurostimulation for Epilepsy

RNS shares some features with DBS, but is differentiated by its use of direct cortical stimulation and by its use in both monitoring and stimulation. The RNS system provides stimulation in response to detection of specific epileptiform patterns, while DBS provides continuous or intermittent stimulation at pre-programmed settings.

Development of the RNS system arose observations related to the effects of cortical electrical stimulation for seizure localization. It has been observed that electrical cortical stimulation can terminate induced and spontaneous electrographic seizure activity in humans and animals. Individuals with epilepsy may undergo implantation of subdural monitoring electrodes for the purposes of seizure localization, which at times have been used for neurostimulation to identify eloquent brain regions. Epileptiform discharges that occur during stimulation for localization can be stopped by a train of neighboring brief electrical stimulations.

In tandem with the recognition that cortical stimulation can stop epileptiform discharges was development of fast pre-ictal seizure prediction algorithms. These algorithms  interpret  electrocorticographic data from detection leads situated over the cortex. The RNS process thus includes electrocorticographic monitoring via cortical electrodes, analysis of data through a proprietary seizure detection algorithm, and delivery of electrical stimulation via both cortical and deep implanted electrodes in an attempt to halt a detected epileptiform discharge.

One system, the Neuropace RNS® System, is currently approved by FDA and is commercially available. The system consists of an implantable neurostimulator, a cortical strip lead, implantable components and accessories, a tablet and telemetry wand, an individual data management system, a remote monitor for use by the individual to upload data to the data management system, and a magnet for individuals to withhold therapy or to activate electrocorticograhic storage. The responsive neurostimulation stimulator and implant monitor the brain’s electrical activity and deliver electrical stimulation when warranted. Before device implantation, the individual undergoes seizure localization, which includes inpatient video-electroencephalographic monitoring and magnetic resonance imaging for detection of epileptogenic lesions. Additional testing may include electroencephalography with intracranial electrodes, intraoperative or extraoperative stimulation with subdural electrodes, additional imaging studies, and/or neuropsychological testing, and intracarotid amytal testing (also referred to as Wada testing). The selection and location of the leads are based on the location of seizure foci. Cortical strip leads are recommended for seizure foci on the cortical surface, while the depth leads are recommended for seizure foci beneath the cortical surface. The implantable neurostimulator and cortical and/or depth leads are implanted intracranially. The neurostimulator is initially programmed in the operating room to detect electrocorticographic activity. Responsive therapy is initially set up using standard parameters from the electrodes from which electrical activity is detected. Over time, the responsive stimulation settings are adjusted on the basis of electrocorticography data, which are collected by the individual through interrogation of the device with the telemetry wand and transmitted to the data management system.

Responsive Neurostimulation for Seizure Monitoring

Although the intent of the electrocorticography component of the RNS system is to provide input as a trigger for neurostimulation, it also provides continuous seizure mapping data (chronic unlimited cortical electrocorticography [CURE]) that may be used by practitioners to evaluate indivials’ seizures. In particular, the seizure mapping data have been used for surgical planning of individuals who do not experience adequate seizure reduction with RNS placement. Several studies have described the use of the RNS in evaluating seizure foci for epilepsy surgery or for identifying whether seizure foci are unilateral.

KEY POINTS:

The most recent literature review was updated through February 22, 2024.

Summary of Evidence

For individuals who have refractory focal epilepsy who receive responsive neurostimulation (RNS), the evidence includes an industry-sponsored randomized controlled trial (RCT), which was used for Food and Drug Administration approval of the NeuroPace® RNS System, as well as several published follow-up analyses. Relevant outcomes are symptoms, morbid events, quality of life, and treatment-related mortality and morbidity. The RCT was well designed and well conducted; it reported that RNS is associated with improvements in mean seizure frequency in individuals with refractory focal epilepsy, with an absolute difference in change in seizure frequency of about 20% between groups; however, the percentage of treatment responders with at least a 50% reduction in seizures did not differ from sham control. Overall, the results suggested a modest reduction in seizure frequency in a subset of individuals. The number of adverse events reported in the available studies are low, although the data on adverse events were limited because small study samples. Generally, individuals who are candidates for RNS are severely debilitated and have few other treatment options, so the benefits are likely high relative to the risks. In particular, individuals who are not candidates for respective epilepsy surgery and have few treatment options may benefit from RNS. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

No relevant clinical practice guidelines were identified.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

RNS System, NeuroPace®, epilepsy, partial seizures, responsive neurostimulation, electrocorticography, chronic unlimited cortical electrocorticography, CURE, Responsive Cortical Stimulation

APPROVED BY GOVERNING BODIES:

In November 2013, the NeuroPace RNS® System (Neuropace) was approved by the FDA through the premarket approval process for the following indication:

“The RNS® System is an adjunctive therapy in reducing the frequency of seizures in individuals 18 years of age or older with partial onset seizures who have undergone diagnostic testing that localized no more than two epileptogenic foci, are refractory to 2 or more antiepileptic medications, and currently have frequent and disabling seizures (motor partial seizures, complex partial seizures and/ or secondarily generalized seizures). The RNS® System has demonstrated safety and effectiveness in patients who average 3 or more disabling seizures per month over the three most recent months (with no month with fewer than 2 seizures), and has not been evaluated in patients with less frequent seizures.”

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP:  Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING: 

There are no specific CPT codes for the insertion of this device. It would be reported with the CPT codes for insertion of a neurostimulator such as the following:

CPT Codes:  

HCPCS Codes:

REFERENCES:

1. Anderson WS, Kossoff EH, Bergey GK, et al. Implantation of a responsive neurostimulator device in patients with refractory epilepsy. Neurosurg Focus. Sep 2008; 25(3):E12.
2. Costa J, Fareleira F, Ascencao R, et al. Clinical comparability of the new antiepileptic drugs in refractory partial epilepsy: a systematic review and meta-analysis. Epilepsia. Jul 2011; 52(7):1280-1291.
3. de Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. The Lancet.378(9800): 1388-1395.
4. DiLorenzo DJ, Mangubat EZ, Rossi MA, et al. Chronic unlimited recording electrocorticography-guided resective epilepsy surgery: technology-enabled enhanced fidelity in seizure focus localization with improved surgical efficacy. J Neurosurg. Jun 2014; 120(6):1402-1414.
5. FDA. Summary of Safety and Effectiveness Data: RNS System 2013.
6. Fisher RS. Therapeutic devices for epilepsy. Ann Neurol. Feb 2012; 71(2):157-168.
7. Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. Apr 2017; 58(4):522-530.
8. Fridley J, Thomas JG, Navarro JC, et al. Brain stimulation for the treatment of epilepsy. Neurosurg Focus. Mar 2012; 32(3):E13.
9. Heck CN, King-Stephens D, Massey AD, et al. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial. Epilepsia. Mar 2014; 55(3):432-441.
10. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
11. King-Stephens D, Mirro E, Weber PB, et al. Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography. Epilepsia. Jun 2015; 56(6):959-967. 
12. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc TaskForce of the ILAE Commission on Therapeutic Strategies. Epilepsia. Jun 2010; 51(6): 1069-77.
13. Loring DW, Kapur R, Meador KJ, et al. Differential neuropsychological outcomes following targeted responsive neurostimulation for partial-onset epilepsy. Epilepsia. Nov 2015; 56(11):1836-1844.
14. Meador KJ, Kapur R, Loring DW, et al. Quality of life and mood in patients with medically intractable epilepsy treated with targeted responsive neurostimulation. Epilepsy Behav. Apr 2015; 45:242-247.
15. Morrell MJ, RNS System in Epilepsy Study Group. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology. Sep 27 2011; 77(13):1295-1304.
16. Nair DR, Laxer KD, Weber PB, et al. Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy. Neurology. Sep 01 2020; 95(9): e1244-e1256.
17. Neuropace, Inc. RNS(R) System Physician Manual for the RNS(R) Neurostimulator Model RNS-320. Revised February 2020.
18. Noe K, Sulc V, Wong-Kisiel L, et al. Long-term outcomes after nonlesional extratemporal lobe epilepsy surgery. JAMA Neurol. Aug 2013; 70(8):1003-1008. 
19. Skrehot HC, Englot DJ, Haneef Z. Neuro-stimulation in focal epilepsy: A systematic review and meta-analysis. EpilepsyBehav. May 2023; 142: 109182.
20. Spencer D, Gwinn R, Salinsky M, et al. Laterality and temporal distribution of seizures in patients with bitemporal independent seizures during a trial of responsive neurostimulation. Epilepsy Res. Feb 2011; 93(2-3):221-225.
21. Wiebe S, Blume WT, Girvin JP, et al. A Randomized, Controlled Trial of Surgery for Temporal-Lobe Epilepsy. N Engl J Med. 2001; 345(5):311-318.
22. Xue-Ping W, Hai-Jiao W, Li-Na Z et al. Risk factors for drug-resistant epilepsy: A systematic review and meta-analysis. Medicine (Baltimore). 2019 Jul; 98(30).

POLICY HISTORY:

Medical Policy Panel, November 2014

Medical Policy Group, November 2014 (5): Creation of new policy for coverage of Responsive Neurostimulation for the treatment of Refractory Partial Epilepsy when certain criteria per the policy are met.

Medical Policy Administration Committee, December 2014

Available for comment December 2, 2014 through January 16, 2015

Medical Policy Panel, April 2016

Medical Policy Group, April 2016 (6): Updates to Description, Key Points, & References. No change in policy statement.

Medical Policy Panel, April 2017

Medical Policy Group, May 2017 (6): Updates to Key points and references. No change to policy statement.

Medical Policy Panel, April 2018

Medical Policy Group, April 2018 (6): Updates to Policy Title, Description, Key Points, and Key Words. “Partial” seizures now referred to in literature as “Focal” seizures.

Medical Policy Group, December 2018:  2019 Annual Coding Update.  Added CPT code 95836 to the Current coding section. Removed incorrect code 95871 and added revised verbiage for code 95970.

Medical Policy Panel, April 2019

Medical Policy Group, May 2019 (3): 2019 Updates to Key Points, References, and Key Words: added: responsive neurostimulation, electrocorticography, chronic unlimited cortical electrocorticography, and CURE. No changes to policy statement or intent.

Medical Policy Group, October 2019 (3): 2019 Updates to Key Points and Key Words: Added: Responsive Cortical Stimulation. No changes to policy statement or intent.

Medical Policy Panel, April 2020

Medical Policy Group, May 2020 (3): 2020 Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. No changes to policy statement or intent.

Medical Policy Panel,  April 2021

Medical Policy Group, May 2021 (3): 2021 Updates to Key Points and References. No changes to policy statement or intent.

Medical Policy Panel, April 2022

Medical Policy Group, April 2022 (3): 2022 Updates to Key Points and References. No changes to policy statement or intent.

Medical Policy Panel, April 2023

Medical Policy Group, May 2023 (3): 2023 Updates to Description, Key Points, Practice Guidelines and Position Statements, Benefit Applications, and References. No changes to policy statement or intent.

Medical Policy Group, November 2023: 2024 Annual CPT Coding Update. Added 61889,61891,61892.

Medical Policy Panel, April 2024

Medical Policy Group, May 2024 (3): Updates to Description and References. No changes to policy statement or intent.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.