mp-574 - Medical Policies - Alabama
Responsive Neurostimulation for the Treatment of Refractory Focal Epilepsy
Policy Number: MP-574
Latest Review Date: April 2022
Responsive Neurostimulation (e.g., NeuroPace RNS System) may be considered medically necessary for patients 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 not medically necessary and investigational for all other indications.
*Contraindications for RNS placement include more than three 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.
Medical Therapy for Seizures
Standard therapy for seizures, including focal seizures, includes treatment with one or more of variety of antiepileptic drugs (AEDs). Advances have occurred with the development and approval of newer AEDs, including oxcarbazepine, lamotrigine, topiramate, gabapentin, pregabalin, levetiracetam, tiagabine, and zonisamide. However, response to AEDs is less than ideal: One systematic review of comparisons between multiple newer AEDs for refractory focal epilepsy reported an overall average responder rate in the treatment groups of 34.8%. As a result, there are substantial numbers of patients who 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, one RCT 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 rates of freedom from seizures of 52%, with 28% of seizure-free individuals able to discontinue AEDs. Selection of appropriate patients for epilepsy surgery is important, as those with nonlesional extratemporal lobe epilepsy have worse outcomes after surgery than those with nonlesional temporal lobe epilepsy. Some patients 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 the VNS’s therapeutic effects 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, and has been most widely used in the treatment of Parkinson disease and other movement disorders, but has also been investigated for epilepsy. DBS of the anterior thalamic nuclei has been studied in 1RCT, 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 the fact that the device performs both monitoring and stimulation functions. 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 out of 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. Patients 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. A train of neighboring brief electrical stimulations can stop Epileptiform discharges that occur during stimulation for localization.
In tandem with the recognition that cortical stimulation may be able to stop epileptiform discharges was the development of fast pre-ictal seizure prediction algorithms. These algorithms involve the interpretation of electrocorticographic data from detection leads 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 to 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, a depth lead, a programmer and telemetry wand, and a patient data management system. Before device implantation, the patient undergoes seizure localization, which includes inpatient video-EEG monitoring and magnetic resonance imaging for detection of epileptogenic lesions. Additional testing may also include EEG with intracranial electrodes, intraoperative or extra-operative stimulation with subdural electrodes, additional imaging studies, and/or neuropsychological testing and intracarotid Amytal (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 patient 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 patients’ seizures. In particular, the seizure mapping data have been used for surgical planning for patients 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.
The most recent literature review was updated through January 17, 2022.
Summary of Evidence
For individuals who have refractory focal epilepsy who receive responsive neurostimulation (RNS), the evidence includes one industry-sponsored randomized controlled trial (RCT), which was used for Food and Drug Administration approval of the NeuroPace® RNS System, as well as case series. Relevant outcomes are symptoms, morbid events, quality of life, and treatment-related mortality and morbidity. The pivotal trial was well designed and well conducted; it reported that RNS is associated with improvements in mean seizure frequency in patients with refractory focal epilepsy, with an absolute difference in change in seizure frequency of about 20% between groups, though 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 patients. The number of adverse events reported in the available studies is low, although the data on adverse events were limited because small study samples. Generally, patients 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, patients 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
American Academy of Neurology
In 2013, the guideline subcommittee of the American Academy of Neurology issued a guideline on vagus nerve stimulation for the treatment of epilepsy. The guidelines make the following recommendations: Vagus nerve stimulation (VNS) may be considered for seizures in children for Lennox-Gastaut syndrome‒associated seizures and for improving mood in adults with epilepsy (level C); VNS may be considered to have improved efficacy over time (level C). Children should be monitored carefully for site infection after VNS implantation. More information is needed on the treatment of primary generalized epilepsy in adults. Only one Class II article addresses this population. The RNS system is not mentioned in these guidelines.
U.S. Preventive Services Task Force Recommendations
RNS System, NeuroPace®, epilepsy, partial seizures, responsive neurostimulation, electrocorticography, chronic unlimited cortical electrocorticography, CURE, Responsive Cortical Stimulation
APPROVED BY GOVERNING BODIES:
In November 2013, FDA approved the NeuroPace RNS® System (Neuropace Inc., Mountain View, CA) 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.”
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. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.
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:
Twist drill or burr hole(s) for implantation of neurostimulator electrodes, cortical
Craniectomy or craniotomy for implantation of neurostimulator electrodes, cerebral, cortical
Twist drill, burr hole, craniotomy, or craniectomy with stereotactic implantation of neurostimulator electrode array in subcortical site (e.g., thalamus, globus pallidus, subthalamic nucleus, periventricular, periaqueductal gray), without use of intraoperative microelectrode recording; first array
; each additional array (List separately in addition to primary procedure)
Revision or removal of intracranial neurostimulator electrodes
Insertion or replacement of cranial neurostimulator pulse generator or receiver, direct or inductive coupling; with connection to a single electrode array
; with connection to 2 or more electrode arrays
Revision or removal of cranial neurostimulator pulse generator or receiver
Electrocorticogram from an implanted brain neurostimulator pulse generator/transmitter, including recording, with interpretation and written report, up to 30 days (Effective 01/01/2019)
Electronic analysis of implanted neurostimulator pulse generator/transmitter (e.g., contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with brain, cranial nerve, spinal cord, peripheral nerve, or sacral nerve, neurostimulator pulse generator/transmitter, without programming
Implantable neurostimulator electrode, each
Implantable neurostimulator pulse generator, single array, non-rechargeable, includes extension
Implantable neurostimulator pulse generator, dual array, non-rechargeable, includes extension
- 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.
- Bercu MM, Friedman D, Silverberg A, et al. Responsive neurostimulation for refractory epilepsy in the pediatric population: A single-center experience. Epilepsy Behav. Nov 2020; 112: 107389.
- Bergey GK, Morrell MJ, Mizrahi EM, et al. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology. Feb 24 2015; 84(8):810-817.
- Child ND, Stead M, Wirrell EC, et al. Chronic subthreshold subdural cortical stimulation for the treatment of focal epilepsy originating from eloquent cortex. Epilepsia. Mar 2014; 55(3):e18-21.
- 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.
- Cox JH, Seri S, Cavanna AE. Clinical utility of implantable neurostimulation devices as adjunctive treatment of uncontrolled seizures. Neuropsychiatr Dis Treat. 2014; 10:2191-2200.
- 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.
- 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.
- Enatsu R, Alexopoulos A, Bingaman W, et al. Complementary effect of surgical resection and responsive brain stimulation in the treatment of bitemporal lobe epilepsy: a case report. Epilepsy Behav. Aug 2012; 24(4):513-516.
- FDA. Summary of Safety and Effectiveness Data: RNS System 2013. Accessed March 4, 2020
- Fisher RS. Therapeutic devices for epilepsy. Ann Neurol. Feb 2012; 71(2):157-168.
- 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.
- Fridley J, Thomas JG, Navarro JC, et al. Brain stimulation for the treatment of epilepsy. Neurosurg Focus. Mar 2012; 32(3):E13.
- Gooneratne IK, Green AL, Dugan P, et al. Comparing neurostimulation technologies in refractory focal-onset epilepsy. J Neurol Neurosurg Psychiatry. Nov 2016; 87(11):1174-1182.
- Guideline Development Subcommittee of the American Academy of Neurology. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the guideline development subcommittee of the American Academy of Neurology. 2013; www.aesnet.org/sites/default/files/file_attach/Guidelines/Neurology-2013-Morris-1453-9.pdf.
- 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.
- IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
- 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.
- Kossoff EH, Ritzl EK, Politsky JM, et al. Effect of an external responsive neurostimulator on seizures and electrographic discharges during subdural electrode monitoring. Epilepsia. Dec 2004; 45(12):1560-1567.
- Kwan P, Arzimanoglou A, Berg AT et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010 Jun; 51(6).
- Lee B, Zubair MN, Marquez YD, et al. A single-center experience with the neuropace rns system: a review of techniques and potential problems. World Neurosurg. Sep 2015; 84(3):719-726.
- 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.
- 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.
- 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.
- Morris GL, 3rd, Gloss D, Buchhalter J, et al. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. Oct 15 2013; 81(16):1453-1459.
- 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.
- Neuropace, Inc. RNS(R) System Physician Manual for the RNS(R) Neurostimulator Model RNS-320. Revised February 2020. https://www.neuropace.com/manuals/RNS_System_Physician_Manual.pdf.Accessed March 5, 2020.
- NeuroPace. NeuroPace: RNS System User Manual [Rev Date 04/2015]. 2015; http://www.neuropace.com/wpcontent/uploads/2015/11/UserManual.pdf. Accessed March 9, 2018.
- 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.
- Smith JR, Fountas KN, Murro AM, et al. Closed-loop stimulation in the control of focal epilepsy of insular origin. Stereotact Funct Neurosurg. 2010; 88(5):281-287.
- 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.
- 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.
- 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).
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.
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.