Responsive Neurostimulation for the Treatment of Refractory Focal Epilepsy

POLICY NUMBER

A.7.01.143

DESCRIPTION

Approximately one-third of individuals with epilepsy do not respond to typical first-line therapy with antiepileptic medications. Seizures that occur in these individuals are referred to as refractory or drug-resistant. In individuals with refractory epilepsy, combination antiepileptic therapy often results in increased risk of adverse events. Other nonpharmacologic treatment options are available, including surgical approaches, ketogenic diet, and responsive neurostimulation. One responsive neurostimulation 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, which include newer antiepileptic drugs, such as oxcarbazepine, lamotrigine, topiramate, gabapentin, pregabalin, levetiracetam, tiagabine, and zonisamide. Currently, response to antiepileptic drugs is less than ideal: one systematic review comparing newer antiepileptic drugs for refractory focal epilepsy reported an overall average responder rate in treatment groups of 34.8%. As a result, a substantial number 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 randomized controlled trial 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 5-year freedom from seizure rates of 52%, with 28% of seizure-free individuals able to discontinue antiepileptic drugs. Selection of appropriate individuals 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 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 neurologic 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 has been widely used for refractory epilepsy, following U.S. Food and Drug Administration approval of a vagus nerve stimulation device in 1997 and two randomized controlled trials evaluating vagus nerve stimulation in epilepsy. Although the mechanism of action for vagus nerve stimulation is not fully understood, vagus nerve stimulation is thought to 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 of deep brain nuclei (deep brain stimulation) 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, and has been investigated for treating epilepsy. Deep brain stimulation of the anterior thalamic nuclei was studied in a randomized control trial, the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy trial, but deep brain stimulation is not currently approved by the 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

Responsive neurostimulation shares some features with deep brain stimulation, but is differentiated by its use of direct cortical stimulation and by its use in both monitoring and stimulation. The responsive neurostimulation system provides stimulation in response to detection of specific epileptiform patterns, while deep brain stimulation provides continuous or intermittent stimulation at preprogrammed settings.

Development of the responsive neurostimulation system arose from 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 the development of fast pre-ictal seizure prediction algorithms. These algorithms interpret electrocorticographic data from detection leads situated over the cortex. The responsive neurostimulation 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 device, the NeuroPace RNS® System, is currently approved by the FDA and is commercially available.

Responsive Neurostimulation for Seizure Monitoring

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

This policy does not further address the use of responsive neurostimulation exclusively for seizure monitoring.

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 2 epileptogenic foci, are refractory to two 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 two seizures), and has not been evaluated in patients with less frequent seizures.”

Related medical policies –

• Vagus Nerve Stimulation

• Deep Brain Stimulation

POLICY

Responsive neurostimulation may be considered medically necessary for individuals with focal epilepsy who meet ALL of the following criteria:

• Are 18 years or older; AND

• Have a diagnosis of focal seizures with 1 or 2 well-localized seizure foci identified; AND

• Have an average of 3 or more disabling seizures (eg, motor focal seizures, complex focal seizures, or secondary generalized seizures) per month over the prior 3 months; AND

• Are refractory to medical therapy (have failed 2 or more appropriate antiepileptic medications at therapeutic doses); AND

• Are not candidates for focal resective epilepsy surgery (eg, have an epileptic focus near eloquent cerebral cortex; have bilateral temporal epilepsy); AND

• Do not have contraindications for responsive neurostimulation device placement (see Policy Guidelines section).

Responsive neurostimulation is considered investigational for all other indications.

POLICY EXCEPTIONS

Federal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Contraindications for responsive neurostimulation device placement include 3 or more specific seizure foci, presence of primary generalized epilepsy, or presence of a rapidly progressive neurologic disorder.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting. 

POLICY HISTORY

04/09/2015: Approved by Medical Policy Advisory Committee.

08/31/2015: Medical policy revised to add ICD-10 codes.

05/31/2016: Policy number A.7.01.143 added.

07/06/2016: Policy description updated regarding responsive neurostimulation for seizure monitoring. Policy statements unchanged.

05/24/2017: Policy description updated regarding focal-onset seizures and responsive neurostimulation for seizure monitoring. Policy statements unchanged.

05/09/2018: "Partial epilepsy" changed to "focal epilepsy" throughout policy to be consistent with current terminology.

12/19/2018: Code Reference section updated to add new CPT codes 95983 and 95984. Revised code descriptions for CPT codes 95970 and 95971, effective 01/01/2019.

05/10/2019: Policy description updated regarding focal-onset seizures and devices. Policy statements unchanged.

06/11/2020: Policy description updated to remove information regarding seizures and seizure disorders. Added "device" to last bullet point. Code Reference section updated to remove deleted CPT codes 95978 and 95979.

07/15/2021: Policy description updated regarding patients with refractory epilepsy. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

05/31/2022: Policy reviewed; no changes.

05/12/2023: Policy description updated regarding focal seizures. Policy statement updated to change "patients" to "individuals."

12/21/2023: Code Reference section updated to add new 2024 CPT codes 61889, 61891, and 61892, effective 01/01/2024.

05/20/2024: Policy description updated to change "patients" to "individuals." Policy statements unchanged.

06/06/2025: Policy reviewed; no changes.

SOURCE(S)

Blue Cross and Blue Shield Association Policy # 7.01.143

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

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