Medical Policy

This document addresses the use of deep brain stimulation (DBS) and responsive neurostimulation (RNS). These technologies involve the use of electrical stimulation of a specific site on or within the brain via implanted electrodes that are connected to a pulse generator. These forms of electrical stimulation are used in the treatment of intractable movement disorders characterized by involuntary tremors or muscle contractions as well as for seizure and other neurological disorders.

Note: Please see the following related documents for additional information:

• MED.00057 MRI Guided High Intensity Focused Ultrasound Ablation for Non-Oncologic Indications

Note: For a high-level overview of this document, please see “Summary for Members and Families” below.

I. Deep Brain Stimulation

Medically Necessary:

Parkinson disease

Unilateral or bilateral deep brain stimulation is considered medically necessary for individuals with Parkinson disease when the following criteria have been met:

1. A minimal score of 30 points on the motor portion of the Unified Parkinson Disease Rating Scale (UPDRS) when the individual has been without medication for 12 hours; and
2. Either of the following:
   1. Motor complications of therapy that cannot be controlled pharmacologically; or
   2. Tremor from Parkinson disease cannot be controlled pharmacologically.

Essential tremor

Unilateral or bilateral deep brain stimulation is considered medically necessary for individuals with medically refractory essential tremor.

Primary dystonia

Unilateral or bilateral deep brain stimulation is considered medically necessary for individuals with primary dystonia when the following criteria have been met:

1. Stimulated area is the subthalamic nucleus or globus pallidus; and
2. Dystonia is all of the following:
   1. Chronic; and
   2. Cannot be controlled pharmacologically; and
   3. Has a significant effect upon daily activity; and
   4. Not due to a secondary cause such as stroke, cerebral palsy, tumor, trauma, infection, multiple sclerosis, other neurodegenerative diseases, or medications.

Obsessive Compulsive Disorder

Bilateral deep brain stimulation is considered medically necessary for individuals with obsessive compulsive disorder when the following criteria have been met:

1. Stimulated area is the striatal axis; and
2. Well documented obsessive compulsive disorder for 5 years or longer; and
3. Severe functional impairment as indicated by a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 26 or greater despite conservative therapy meeting criteria 1 and 2 below:
   1. Cognitive-behavioral therapy with a minimum of 20 sessions involving personal (in-person or videoconference) interaction between the individual and a certified behavioral specialist; and
   2. Pharmacotherapy including both a and b below:
      1. A trial of clomipramine and at least two other serotonin-reuptake inhibitors at the maximum recommended dose or tolerated dose for at least 12 weeks; and
      2. Augmentation of at least one serotonin-reuptake inhibitor trial with first- or second-generation neuroleptic over a period of at least 1 month;
         and
4. Documentation indicates the individual or caregiver will be able to manage device in post-operative period; and
5. Absence of all of the following:
   1. Contraindication to surgery including, but not limited to, any of the following:
      1. Significant neurological condition (for example, history of stroke, hypoxic brain injury, severe head trauma, cranial neoplasm, movement disorder); or
      2. Contraindication and/or inability to undergo MRI; or
      3. Clinically significant abnormality on MRI that may impair deep brain stimulator implantation; or
      4. Clinically significant medical condition;
         and
   2. Current significant psychological condition including, but not limited to, any of the following:
      1. Active substance use disorder within the past 6 months; or
      2. Manic episode in the preceding 3 years; or
      3. Psychotic disorder within the past 3 years; or
      4. Imminent risk of suicide; or
      5. Severe personality disorder.

Epilepsy

Unilateral or bilateral deep brain stimulation is considered medically necessary for individuals with epilepsy when the following criteria have been met:

1. Stimulated area is the anterior nucleus of the thalamus; and
2. Focal partial onset seizures with or without generalized seizure; and
3. Refractory to two (2) or more antiepileptic medications; and
4. Currently having an average of three (3) or more disabling seizures (for example, motor partial seizures, complex partial seizures, or secondary generalized seizures) per month over the most recent three months; and
5. Absence of progressive neurological or medical conditions such as brain tumors or neurodegenerative disease; and
6. Non-epileptic seizures have been ruled out as the sole seizure etiology.

Revision or replacement

Revision or replacement of a deep brain stimulator or battery for such devices is considered medically necessary when the following criteria are met:

1. The individual has demonstrated clinical benefit from the stimulation; and
2. One or both of the following criteria are met:
   1. The device has malfunctioned or is no longer working as intended; or
   2. The neurostimulator or battery is within 12 months of its expected maximum service life.

Investigational and Not Medically Necessary:

Deep brain stimulation is considered investigational and not medically necessary when criteria above have not been met.

Revision or replacement of a deep brain stimulator, or battery for such devices, is considered investigational and not medically necessary when the criteria above have not been met.

II. Responsive Neurostimulation

Medically Necessary:

Responsive neurostimulation is considered medically necessary for individuals with epilepsy when the following criteria have been met:

1. 18 years of age or older*
2. Partial onset seizures; and
3. Diagnostic testing has localized no more than two (2) epileptogenic foci; and
4. Refractory to two (2) or more antiepileptic medications; and
5. Currently having an average of three (3) or more disabling seizures (for example, motor partial seizures, complex partial seizures, or secondary generalized seizures) per month over the most recent three months.

* Note: A neurosurgeon with experience in the pediatric population may request further consideration of a case of an individual under 18 years old when the criteria above are otherwise met by contacting a Medical Director. For further information, see Rationale section: Age Considerations for RNS Therapy.

Revision or replacement of a responsive neurostimulation system, or battery for such devices, is considered medically necessary when the following criteria are met:

1. The individual has demonstrated clinical benefit from the stimulation; and
2. One or both of the following criteria are met:
   1. The device has malfunctioned or is no longer working as intended; or
   2. The neurostimulator or battery is within 12 months of its expected maximum service life.

Investigational and Not Medically Necessary:

The use of responsive neurostimulation is considered investigational and not medically necessary when the criteria above have not been met.

Revision or replacement of a responsive neurostimulator or battery for such devices is considered investigational and not medically necessary when the criteria above have not been met.

This document describes clinical studies and expert recommendations, and explains when deep brain stimulation (DBS) and responsive neurostimulation (RNS) are clinically appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

DBS and RNS are treatments that use small electrical devices placed in the brain to help control symptoms related to brain activity such as severe movement disorders, epilepsy (seizures), or certain mental health conditions, such as obsessive-compulsive disease (OCD), when other treatments have not worked. DBS sends steady electrical signals to certain brain areas, while RNS monitors brain activity and sends signals only when needed. Studies show they can reduce symptoms like tremors or seizures in some people. However, they require brain surgery and carry risks such as infection, bleeding, mood changes, or problems with the device. Careful selection of individuals to undergo implantation of these devices is important to balance benefits and risks.

What the Studies Show

DBS has been studied for conditions such as Parkinson disease, essential tremor, dystonia, obsessive compulsive disorder, and epilepsy. High-quality studies show DBS can improve movement symptoms and reduce seizures in people whose symptoms do not improve with medication. For example, some studies found large reductions in tremors or seizure frequency. In people with obsessive compulsive disorder, studies show symptom scores improved, but most studies were small and results varied. Some people had serious side effects such as bleeding in the brain, infection, mood changes, or seizures. These risks show that, while DBS can help, it must be used carefully.

RNS is mainly used for epilepsy. It works by detecting abnormal brain activity and sending a pulse to stop a seizure before it starts. Studies show that in adults RNS can reduce seizures over time, and some people have long periods without seizures. However, benefits may increase slowly, and not everyone responds. Risks include infection, bleeding, memory problems, or mood changes. For children, the evidence is not strong, with the available studies including small numbers of people and other limitations. Additionally, in children, problems have been observed related to their growth and how the placement of the implanted device may or may not move over time. Further studies are needed to better understand how that changes the way these devices work as the child grows.

Overall, both DBS and RNS can help some people with severe conditions, but they do not cure disease and require ongoing monitoring.

When is Deep Brain Stimulation (DBS) Clinically Appropriate?

Deep brain stimulation (DBS) may be appropriate in these situations:

• Parkinson disease when symptoms are severe, not well controlled by medication, and movement problems or tremors continue despite treatment.
• Essential tremor that does not improve with medication.
• Primary dystonia when symptoms are long-lasting, affect daily life, and do not improve with medication.
• Obsessive compulsive disorder in adults with severe symptoms for at least 5 years, and symptoms do not improve after therapy and multiple medications, and there are no major safety concerns for surgery.
• Epilepsy with focal seizures when:
  • Seizures do not improve after at least two medications; and
  • The person has frequent, disabling seizures; and
  • Other causes of seizures have been ruled out.
• Replacement or repair of a DBS device when it has helped before, and the device is not working properly, or the battery is near the end of its life.

When is Responsive Neurostimulation (RNS) Clinically Appropriate?

Responsive neurostimulation (RNS) may be appropriate in these situations:

• Epilepsy with partial onset seizures when:
  • The person is 18 years of age or older; and
  • Seizures do not improve after trying at least two medications; and
  • Doctors can identify no more than one or two areas in the brain where seizures start; and
  • The person has frequent, disabling seizures.
• Replacement or repair of an RNS device when it has helped before, and the device is not working properly or the battery is near the end of its life.

When is this not Clinically Appropriate?

DBS or RNS is not clinically appropriate when the conditions listed above are not met. Studies show these treatments work best only in carefully selected people. Using them outside these groups has not been proven to improve health and may expose people to unnecessary risks such as surgery complications, infections, or mood changes.

(Return to Description/Scope)

Summary

Deep brain stimulation (DBS) is well established for several neurologic movement disorders, especially Parkinson disease, essential tremor, dystonia, and some cases of medically refractory epilepsy. Evidence from randomized trials and long-term follow-up studies shows that DBS can significantly improve motor symptoms, tremor, dystonia severity, and seizure frequency in carefully selected individuals. However, device-related complications, infections, mood changes, and other adverse events remain important risks. FDA approvals support DBS for Parkinson disease, essential tremor, dystonia under Human Device Exemption (HDE), obsessive-compulsive disorder (OCD) under HDE, and epilepsy in specific adult populations.

For OCD, evidence suggests that DBS can reduce symptom severity in a highly selected group of individuals with severe, treatment-refractory disease, but the studies are generally small and heterogeneous, and adverse psychiatric and neurologic events can occur. Current guideline support is strongest for bilateral subthalamic nucleus DBS, with some support for nucleus accumbens or bed nucleus of the stria terminalis targets. Studies emphasize the need for strict inclusion and exclusion criteria.

Responsive neurostimulation (RNS) is FDA approved for adults with focal epilepsy involving no more than two seizure foci and has shown sustained reductions in seizure frequency over time, with acceptable safety in selected individuals. Pediatric data for RNS and DBS are growing and appear promising, but remain limited, mostly retrospective, and insufficient for broad conclusions.

Overall, both DBS and RNS may provide meaningful benefit for carefully chosen individuals with otherwise refractory disease, but long-term safety concerns require careful individual selection.

Discussion

DBS for Dystonia, Parkinson Disease, and Tremor

Randomized studies have shown that DBS in the globus pallidus, subthalamic nucleus, or thalamus improved the symptoms of medically refractory Parkinson disease (PD). Studies including robotically assisted DBS to treat PD have also shown improvements in disease symptoms (Huang, 2024; Wu, 2024). Additionally, randomized controlled studies have shown that DBS of the thalamus improves the symptoms of essential tremor compared to sham stimulation (Figuerias-Mendez, 2002; Merello, 1999; Obeso, 2001; Rehncrona, 2003; Schuepbach, 2013; Starr, 2025; Vitek, 2020). DBS has become a standard treatment for PD that is refractory to medical therapy. Inclusion criteria for the pivotal trial for DBS use in PD (Obeso, 2001) included the presence of at least two of the three cardinal features of parkinsonism (tremor, rigidity, and bradykinesia), a good response to levodopa, a minimal score of 30 points on the motor portion of the UPDRS when the individual has been without medication for approximately 12 hours, and motor complications that could not be controlled with pharmacologic therapy. The 5-year findings reported by Starr and colleagues provide high-quality evidence confirming the durable effectiveness of subthalamic DBS originally demonstrated by Vitek and colleagues, reinforcing the importance of pre-implant selection criteria, including a minimal baseline UPDRS-III motor score of 30 in the medication-off state and a documented levodopa response.

In 2018, the Congress of Neurological Surgeons (Rughani, 2018) published the following Level I recommendations on DBS for the treatment of Parkinson disease:

• Given that bilateral STN [subthalamic nucleus] DBS is at least as effective as bilateral Gpi [globus pallidus internus] DBS in treating motor symptoms of Parkinson’s disease (as measured by improvements in UPDRS-III [Unified Parkinson’s Disease Rating Scale, part III] scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms.
• There is insufficient evidence to make a generalizable recommendation regarding the target selection for reduction of dyskinesias. However, when the reduction of medication is not anticipated and there is a goal to reduce the severity of “on” medication dyskinesias, the Gpi should be targeted.

On June 12, 2015, the FDA granted Pre-Market Approval (PMA) for the Brio Neurostimulation system to reduce symptoms of Parkinson disease and essential tremor in individuals with symptoms not adequately controlled with drug therapy. The FDA cited two clinical studies supporting the safety and effectiveness of the device. The first included 136 participants with Parkinson disease followed for 3 months after device implantation. The second included 127 participants with essential tremor followed for 6 months. Both studies demonstrated statistically significant improvement in the primary effectiveness endpoints when the device was turned on compared to when it was turned off.

Primary (or idiopathic) dystonia is dystonia that is not due to a secondary cause such as stroke, cerebral palsy, tumor, trauma, infection, multiple sclerosis, medications, or a neurodegenerative disease. In 1997, the Activa^® Dystonia Therapy System (Medtronic, Minneapolis, MN) received PMA from the FDA for unilateral thalamic stimulation for the suppression of tremor in the upper extremity in individuals who are diagnosed with essential tremor or parkinsonian tremor not adequately controlled by medications and for whom the tremor constitutes a significant functional disability (Roper, 2016; Tan, 2016).

In 2003, the FDA granted the Activa^® Dystonia Therapy System a Humanitarian Devices Exemption (HDE) for the treatment of primary dystonia. The FDA’s decision was based on the results of DBS in 201 individuals represented in 34 manuscripts. There were three studies that reported at least 10 cases of primary dystonia. In these studies, clinical improvement ranged from 50% to 88%. A total of 21 children were studied; 81% were older than 7 years. Among these individuals there was about a 60% improvement in clinical scores. The FDA analysis of risk and probable benefit indicated that the only other treatment options for chronic refractory primary dystonia are neurodestructive procedures and DBS provides a reversible alternative.

Volkmann and colleagues (2012) published the results of a randomized controlled trial (RCT) involving 40 participants with severe generalized or segmental idiopathic dystonia. Participants were assigned to either sham or active neurostimulation of the internal globus pallidus. The experimental group received active treatment for 9 months while the control group had an initial 3-month period with their implanted device deactivated (sham treatment), followed by 6 months of active treatment. The initial intention of the study was to cease follow-up at the end of 9 months, but was extended to 5 years. A progressive improvement of dystonia severity beyond 6 months of neurostimulation was predominantly seen in participants with generalized dystonia. Participants with segmental dystonia demonstrated a relatively stable status from 6 months through 5 years. With the exception of speech and swallowing, all motor symptoms as well as the global clinical assessments of dystonia and pain showed significant improvements for up to 5 years. Twenty-one participants experienced serious adverse events that required hospital admission. Sixteen of the 21 serious adverse events were device-related and were caused by technical defects, delayed infection, or migration. All serious adverse events in the original 9-month study phase and 66.6% of events during the long-term extension occurred in participants with generalized dystonia. Fourteen of the 16 events of dysarthria occurred in participants with segmental dystonia. This study demonstrates significant benefits of DBS in individuals with dystonia. However, substantial differences were found in outcomes between participants with generalized vs. segmental dystonia.

Volkmann (2014) reported the results of a double-blind RCT involving 62 participants with cervical dystonia assigned to receive either globus pallidus neurostimulation (n=32) or sham stimulation (n=30). Data were available for 60 participants (97%) at 3 months and 56 participants (90%) at 6 months. At 3 months, the reduction in dystonia severity as measured with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was significantly improved in the experimental group compared to controls (-5.1 points vs. 1.3; p=0.0024). Adverse events were reported in 11 experimental group participants (21 events), with 5 events considered serious. The authors reported 11 serious adverse events (5 in the experimental group participants and 6 in the control group), including infection, device explantation, and electrode dislocation. The results of this trial were considered promising and demonstrate a significant benefit to DBS therapy in individuals with cervical dystonia.

Duga and colleagues (2024) conducted a retrospective single-center cohort study of children with genetic or idiopathic dystonia treated with GPi DBS. The primary outcome was the Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) score. This cohort included 25 participants with a mean follow-up period of 11.4 years. An adjacent meta-analysis included 224 individuals with a mean study follow-up period of 3 years. Overall, mean improvements in BFMDRS-M scores were 41% at 1 year and 33% at the last follow-up in the clinical cohort, and 58.9% at 1 year and 57.2% at the last follow-up in the meta-analysis cohort. This study has some limitations such as its retrospective design and lack of control group but shows the utility of DBS among children with genetic or idiopathic dystonia.

In February of 2024, the FDA expanded premarket approval for the Vercise PC DBS System, Vercise Gervia DBS System, Vercise Genus DBS System (Boston Scientific Neuromodulation Corporation, Valencia, California) to include “Bilateral stimulation of the ventral intermediate nucleus (VIM) of the thalamus for the suppression of disabling upper extremity tremor in adult essential tremor patients whose tremor is not adequately controlled by medications and where the tremor constitutes a significant functional disability.” The original PMA (P150031) and other expanded approvals for the Vercise DBS Systems were approved in 2017, 2019 and 2021 for bilateral stimulation of the subthalamic nucleus and internal globus pallidus and unilateral stimulation of the VIM, respectively. No new clinical data was submitted to support the 2024 expanded approval.

Deep Brain Stimulation (DBS) for Obsessive Compulsive Disorder

On February 19, 2009, the Reclaim™ device (Medtronic Neuro, Minneapolis, MN) received FDA approval under the HDE process. The FDA labeling states that the device is indicated for bilateral stimulation of the anterior limb of the internal capsule (AIC), as an adjunct to medications and as an alternative to anterior capsulotomy for treatment of chronic, severe, treatment-resistant obsessive-compulsive disorder (OCD) in adults who have failed at least three selective serotonin reuptake inhibitors (SSRIs).

The use of DBS for OCD has been studied in multiple RCTs and case series studies, but the vast majority of these involved few participants. This hampers the generalizability of their findings and does not provide a comprehensive picture of the safety hazards (Abelson, 2005; Barcia, 2019; Goodman, 2010; Greenberg, 2006, 2010; Holland, 2020; Huff, 2010; Huys, 2019; Jimenez, 2013; Nuttin, 1999; Polosan, 2019; Rauch, 2006; Roh, 2012; Tyagi, 2019; Voon, 2018; Winter, 2020). Only a small number of RCTs involve populations larger than 15 participants.

Mallet and colleagues (2008) reported preliminary findings of a randomized, double-blind, crossover multicenter study of DBS of the subthalamic nucleus for treatment of refractory OCD. Included participants had received a primary diagnosis of OCD with a disease duration of more than 5 years, a score on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) of more than 25 or one subscale score of more than 15, a score on the Global Assessment of Function (GAF) scale of less than 40, and severity of illness on the Clinical Global Impression (CGI) scale of more than 4. Participants were excluded if they were diagnosed with schizophrenic disorder, bipolar disorder, substance use disorder or dependence (except for dependence on nicotine), cluster A or B personality disorder, current severe major depressive episode, or a risk of suicide. Eighteen participants were enrolled. Of these, 1 withdrew and 1 required removal of the stimulator before randomization because of infection. Of the 16 remaining participants, 14 received bilateral stimulation and the other 2 received unilateral stimulation. Three months after surgery, 8 participants were randomly assigned to receive active stimulation for 3 months, followed by 1 month of washout, then 3 months of sham stimulation (on-off group). The other group followed the same treatment schedule in reverse (off-on group). New or worsening symptoms were classified as adverse events. The primary outcome measure was severity of OCD as assessed by the Y-BOCS measured at the end of each period. The Y-BOCS score was significantly lower at the end of active stimulation than at the end of the sham stimulation (mean score, 19 ± 8 vs. 28 ± 7; p=0.01) independent of the group and the period. No significant carryover effect between treatment phases was detected. Participants who had active stimulation first (on-off group) tended to have a larger treatment effect than the off-on group (p=0.06). Outcomes on secondary measures of global health and functioning were significantly better at the end of the stimulation period. Scores on Montgomery and Åsberg Depression Scale (MADRS), Brief Scale for Anxiety (BSA), neuropsychological ratings, and self-reported disability (Sheehan Disability Scale) did not differ significantly at the end of treatment and sham sessions. Fifteen serious adverse events were reported in 11 participants, the most serious being a parenchymal brain hemorrhage. Transient motor and psychiatric symptoms induced by active stimulation resolved spontaneously or with adjustment of stimulation settings. Seven behavioral adverse events were reported in 5 participants during stimulation. Hypomania was the main psychiatric serious adverse event; symptoms resolved with adjustment of stimulation settings. The authors note that the multicenter design might be a limitation of the study because of variation in targeting of stimulation. In addition, to preserve blinding, stimulation settings were kept below the threshold known to induce adverse effects and may have been too low to reduce symptoms. The authors concluded that these preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD, but it is associated with a substantial risk of serious adverse events.

Denys and colleagues (2010) published the results of an RCT involving 16 participants with OCD with a score greater than 28 on the Y-BOCS and failure of at least two SSRIs. Participants were excluded if they had clinically significant comorbid DSM-IV diagnoses such as schizophrenia, bipolar II disorder, alcohol or substance abuse in the preceding 6 months, and severe personality disorders. Other exclusion criteria included neurologic or medical illnesses that were clinically significant and unstable. Participants underwent bilateral implantation of a DBS device to the nucleus accumbens and then entered an open 8-month treatment phase, followed by a double-blind crossover phase with randomly assigned 2-week periods of active or sham stimulation, ending with an open 12-month maintenance phase. The authors reported that in the open phase, the mean Y-BOCS score decreased by 46%, from 33.7 (3.6) at baseline to 18.0 (11.4) after 8 months (p<0.001). Out of a total of 16 participants, 9 were noted to be responders, with a mean Y-BOCS score decrease of 23.7 (72%). In the double-blind, sham-controlled phase in which data for 14 participants was available, the mean Y-BOCS score difference between active and sham stimulation was 8.3 (25%; p=0.004). Depression and anxiety decreased significantly. Except for mild forgetfulness and word-finding problems, no permanent adverse events were reported.

Luyten and others (2016) described the results of a randomized, double-blind, crossover study of DBS of the anterior limbs of the internal capsule (ALIC) and bed nucleus of the stria terminalis (BST) in 24 participants with OCD. Only 17 participants completed the full trial. Individuals were excluded if they had a current or past psychotic disorder, any clinically significant disorder or medical illness affecting brain function or structure (other than motor tics or Gilles de la Tourette syndrome), or current or unstably remitted substance use disorder. Electrode placement was heterogeneous, with 5 participants bilaterally in the BST, 1 unilaterally in the BST, 2 received stimulation on the BST in one hemisphere and the internal capsule (IC) in the contralateral side, 2 were stimulated bilaterally in the IC or the prereticular zone, 5 bilaterally in the ALIC, and 2 in both the BST and ALIC. Given the radius of the stimulation the investigators concluded that most participants (82%) received stimulation in the BST, and/or IC (41%), or its anterior limb (35%). Multiple other areas adjacent to those areas may have received partial stimulation as well. Y-BOCS scores were significantly improved in the stimulation-on arm of the trial compared to the off arm (37%, p<0.017). Notably, 13 of the 17 crossover participants also had significant Y-BOCS improvements in the off arm, indicating potential for placebo or microlesion effect. Similar results were found on the Hamilton Anxiety and Depression Rating Scales (HAM-A and HAM-D) and GAF scale, with 71%, 54%, and 15-point improvements, respectively (p<0.001 for all). No potential placebo effect was noted for the HAM results. Fourteen participants had their stimulators turned on prematurely in the off arm due to “unbearable worsening of the symptoms”, leading to a median ‘on’ duration of 89 days and median off duration of 44 days. In neuropsychological testing, significant improvements were noted on the Stroop test, Trail Making Test, and Auditory Verbal Learning test indicating improved executive functioning, mental processing and flexibility, and verbal learning and memory. However, no statistics were provided for these comparisons in the supplemental data. At 4 years follow-up, continuous improvement in Y-BOCS, HAM-A, HAM-D, and GAF scores were reported (66%, 58%, 67% and 30 points, respectively; p<0.01 for all). In an analysis of target vs. outcomes, the authors reported that stimulation of the BST was associated with significantly better outcomes when compared to ALIC stimulation (p=0.01). Multiple adverse events were reported throughout the trial, including skeletal fracture (n=6), seizures (n=5), suicide attempt (n=3), intracerebral hemorrhage (n=2), polytrauma (n=2), and obstructive sleep apnea (n=2). The authors concluded that DBS of the ALIC/BST area substantially alleviates symptoms of OCD in treatment refractory individuals. However, they further point out significant concern regarding the incidence of seizures in the study, emerging 2-5 years following initiation of stimulation of the BST, implicating this as a potential hazard.

In 2021, Mosley and colleagues published the results of a randomized, double-blind, sham-controlled trial investigating the effects of DBS at the bed nucleus of the stria terminalis in a sample of 9 Australian participants (mean age 47.9 ± 10.7 years) with severe, treatment-resistant OCD. After a 1-month postoperative recovery phase, participants entered a 3-month randomized phase during which their stimulators were either turned on or remained switched off. After this, participants entered a 12-month open-label stimulation phase incorporating a course of cognitive behavioral therapy (CBT). The primary outcome measure was OCD symptom severity as assessed by Y-BOCS score. In the blinded phase, there was a significant benefit of active stimulation over sham (p=0.025, mean difference 4.9 points). One participant developed an acute implantation effect assessed by a reduction in the intensity of obsessive thoughts for 72 hours post-operatively before returning to baseline. One participant did not reach the target amplitude of 4.5 Volts during the blinded phase due to mild agitation at higher amplitudes, but due to a robust observed symptom reduction, a lower amplitude was selected for chronic stimulation. One participant showed a placebo response to sham stimulation with a 20% reduction in Y-BOCS. After the open phase, the mean reduction in Y-BOCS was 17.4 ± 2.0 points (χ2 (11)=39.9, p=3.7 × 10-5), with 7 participants classified as responders. The addition of CBT resulted in a further Y-BOCS reduction of 4.8 ± 3.9 points (p=0.011). There were nine serious adverse events. One participant had medication adjustments due to non-response to DBS and persistence of clinically significant symptoms. It is noted that this participant was in the stimulation group during the blinded phase of the trial. The participant’s response resulted in five of the serious adverse events due to hospitalization for symptom management. Another participant was readmitted to the hospital on two occasions to manage recurrence of depressive symptoms. One participant developed an infection during the open-label phase necessitating DBS device explantation and exit from the trial. Another device-related serious adverse event required re-siting of a DBS electrode that migrated from target implantation. All participants required replacement of the implantable generator due to battery depletion during the study. The authors noted the small sample size as a limitation of the trial, though it is consistent with other clinical trials of DBS for treatment-resistant psychiatric indications. The study is also limited by the short duration of its blinded phase and lack of long-term follow-up.

Greenberg and colleagues (2010) published the results of a multi-center study involving DBS implantation into the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) in 26 participants with severe treatment-resistant OCD. Participants had a score of greater than or equal to 28 on the Y-BOCS, had failed a minimum of two trials with SSRIs, and had symptoms for a minimum of 5 years. Some of the exclusionary criteria included if there was a history of a current or past psychotic disorder, a manic episode within the preceding 3 years, current or unstably remitted substance use disorder or dependence, a clinical history of severe personality disorder, if there was an imminent risk of suicide, any clinically significant abnormality on MRI, any contraindication or inability to undergo MRI, and any current clinically significant neurological disorder or medical illness except for tic disorders. At the final 36 months post-implant time point, mean Y-BOCS reached 20.9 ± 2.4, down from 34.0 ± 0.5 (p=0.002), and the number of participants meeting criteria for full response (decrease in Y-BOCS ≥ 35) was 61.5% (16/26). A total of 73% of participants had at least a 25% decrease in Y-BOCS. The GAF score was available for 21 participants and rose from a mean of 34.8 ± 1.1 at baseline to 59.05 ± 3.3 at 36 months (p=0.006). Serious adverse events included intracerebral hemorrhage in 2 participants (7.7%) following lead insertion, and both cases resolved spontaneously. Another participant (3.8%) developed generalized tonic-clonic seizures following implantation, necessitating treatment with phenytoin for 1 month postoperatively. Seizures did not recur following cessation of medical therapy. Lead replacement was required in 2 (7.7%) participants due to breakage. Therapy-related complications included 4 cases of increased depression or suicidal ideation in 3 participants (11.5%), increased severity of OCD was reported in 3 participants (11.5%), hypomania in 1 participant (3.8%), and domestic problems/irritability associated with stimulation were reported in 1 participant (3.8%). The authors concluded that their results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target.

In 2015, Alonso and others conducted a meta-analysis of studies addressing the use of DBS for the treatment of OCD. They included 31 studies involving 116 participants in the analysis. The studies mentioned above (Denys, 2010; Greenberg, 2010; Mallet, 2008) were included, and represented 50% of the participant population. The remaining 28 studies accounted for the rest of the participant pool, representing a mean of 2.07 participants per study (range=1-10). Implantation in striatal areas, anterior limb of the internal capsule, ventral capsule and ventral striatum, nucleus accumbens and ventral caudate was reported in 83 participants. Implantation in the subthalamic nucleus was reported in 27 participants, and implantation in the inferior thalamic peduncle was reported in 6 participants. Global percentage of Y-BOCS reduction was estimated at 45.1% and global percentage of responders at 60.0%. The authors reported that better response was associated with older age at OCD onset and presence of sexual/religious obsessions and compulsions. No significant differences were detected in efficacy between targets. There were 5 dropouts reported, and adverse effects were generally reported as mild, transient, and reversible. The authors concluded that their analysis confirms that DBS constitutes a valid alternative to lesional surgery for individuals with severe, therapy-refractory OCD. However, they noted that well-controlled, randomized studies with larger samples are needed to establish the optimal targeting and stimulation conditions and to extend the analysis of clinical predictors of outcome.

In 2021, Hageman and colleagues published a meta-analysis comparing the clinical outcomes of individuals who underwent ablative surgery or DBS. The investigators focused on the efficacy of reducing symptoms, reported adverse events, the effect on depression and anxiety, and the effect on global functioning. Random effects meta-analyses were performed on 38 articles focusing on the efficacy in reducing OCD symptoms as measured by a reduction in the Y-BOCS score and the responder rate (≥ 35% reduction in Y-BOCS score). Responder rates were 48% and 53% after 12 to 16 months and 56% and 57% at last follow-up for ablative surgery and DBS, respectively. The effect sizes in the reduction of Y-BOCS scores were considered very large in both ablative surgery and DBS indicating that they both result in clinically relevant improvements in individuals with treatment-refractory OCD. Regarding these outcomes, meta-regression showed no statistically significant difference between ablative surgery and DBS. Regarding adverse events, meta-regression showed that the difference in occurrence of impulsivity, agitation, and disinhibition between ablative surgery and DBS studies was statistically significant with the rate per patient year being higher for DBS (p=0.024). There was also a trend toward statistically significant (p=0.055) more cases of mania or hypomania in DBS. However, in most cases, these adverse events disappeared spontaneously after a few days or could be managed with adjustment to DBS settings. The authors noted that while healthcare practitioners may be more inclined towards utilization of DBS due to its reversibility, choice of intervention should carefully assess factors such as the risk of developing impulsivity. Some limitations included high heterogeneity between studies, anatomical target differences, differences in stimulation parameters for DBS, lack of control conditions, and a lack of adverse event reporting in many studies.

In 2014, Kohl and colleagues published a systematic review comparing and evaluating the effectiveness of different targeted brain structures for the treatment of OCD. The investigators identified 25 studies including 109 participants reporting on 5 different DBS target structures: the ALIC (n=14), nucleus accumbens (n=37), ventral capsule/ventral striatum (n=29), subthalamic nucleus (n=23), and inferior thalamic peduncle (n=6). The studies included were primarily case reports or case series and all included information on the Y-BOCS as an assessment tool. The follow-up period for most studies was less than 36 months with 11 studies reporting follow-up of 1 year or less. The response rates for the ALIC (75%), nucleus accumbens (45.5%), ventral capsule/ventral striatum (50%), and subthalamic nucleus (57.1%) were similar while the results for the inferior thalamic peduncle was higher (100%). However, the authors caution interpreting that as superiority as the number of cases was low. Serious adverse events included two seizures and three intracerebral hemorrhages. Stimulation related side effects were transient and declined after adjusting parameters. Device related adverse events included breaks in stimulating leads and battery failure, which the authors note could precede unfavorable changes in mood and behavior. Some study limitations included study design and methodology, lack of comparator, and sample size.

In a systematic review, Naesström and colleagues (2016) reviewed available evidence on multiple psychiatric indications for DBS with a focus on therapy-refractory OCD and major depressive disorder. A total of 52 studies met their inclusion criteria describing a total of 286 unique individuals treated with DBS for psychiatric indications. The sample included 18 studies that described 112 individuals treated with DBS for OCD in 6 different anatomical targets, while 9 studies included 100 individuals treated with DBS for major depressive disorder in 5 different targets. Regarding OCD, the studies did not differ substantially regarding inclusion criteria. Participant criteria mostly included: those with severe OCD, defined by a minimum Y-BOCS score of 25 to 28, for at least 5 years; therapy-refractory symptoms after three attempts using SSRIs including clomipramine; additive therapy with a neuroleptic and/or a benzodiazepine; and attendance to a minimum of 16-20 CBT sessions. Regarding the use of DBS in depression, the follow-up intervals and tools for evaluation varied which complicated the comparison. Though many of the included studies demonstrated improvements in OCD, they are limited by their design, lack of randomized controlled data, differing tools for evaluation, and varied definitions of response and remission. Furthermore, there was a lack of consensus on optimal targets for DBS and over half of the studies on its use in OCD included 4 participants or less.

Menchón (2021) published the results of a case series study involving 30 participants with severe to extreme treatment-refractory OCD treated with bilateral DBS of the ALIC. Participants were followed for 12 months. Mean Y-BOCS scores decreased significantly from baseline to 12 months (34.9 vs. 20.2, no p-value provided). At 12 months, the number of participants deemed responders (at least a 35% decrease in Y-BOCS) was 60% (n=18). All participants were reported to have experienced adverse events, with a total of 195 events, including non-specified neurological disorders (n=10), headaches (n=11), anxiety disorders (n=8), sleep disorders/disturbance (n=9), and infections (n=9). The majority were determined to be mild or moderate (89.74%) and 63% were determined to have been device-related. A total of 36 serious adverse events occurred, including worsening OCD (n=9), seizures (n=4), anxiety (n=2) and hypomania (n=2). Adverse events led to temporary cessation of treatment in 8 participants. The majority of events were resolved by the end of testing, but 5% (9 events in 7 participants) were ongoing, including hypothyroidism, worsening emotional instability, dizziness, hypercholesterolemia, gastritis, and implant site pain. A total of 588 acute stimulation-induced effects were reported during visits at which stimulation parameters were adjusted, including hot/cold sensation, mood and anxiety effects, and skin flushing.

Denys (2020) reported the results of a case series study involving 70 participants with refractory OCD treated with bilateral DBS of the ventral ALIC (vALIC). Of these, 16 participants had participated in this group’s previously reported study. In this study, absolute contraindications for DBS were the presence of psychotic disorders, substance use disorder within the past 3 months, and unstable neurological or coagulation disorders. In contrast to their initial study (Denys, 2010), severe comorbid DSM diagnoses such as bipolar disorder, autism, or personality disorder, were instead relative contraindications that relied on the input of a multidisciplinary team to determine appropriateness of treatment with DBS. Concomitant CBT was provided to 57 participants to decrease compulsive behavior and avoidance, and to test DBS setting. The remaining 13 participants did not receive CBT on the basis of good response to DBS alone. At 12 months of active stimulation demonstrated a mean decrease of Y-BOCS scores of 13.5 points (34 at baseline to 20.5, p<0.0001). Overall, 62% (n=36) of participants were reported as responders with a mean Y-BOCS decrease of 20.9 points. Another 17% (n=17%) were determined to be partial responders with mean Y-BOCS decrease of 99 points. There were a total of 22 non-responders (31%) with mean Y-BOCS of 3.3 points. At 12 months HAM-D scores decreased from 21 to 9.8 (p<0.001). Explantation occurred in 2 participants due to infection and these participants underwent subsequent reimplantation within 3 months. Another 6 participants underwent electrode reimplantation or retraction due to poor rooting in the vALIC (n=4), they were implanted too deeply (n=1), or migration (n=1). The number of overall adverse events was not reported. However, stimulation-related adverse events included hypomania (39%), impulsivity (19%), and sleeping disorders (46%). Other adverse events reported included headache (36%), pain around burr holes (17%), pulling of the extension leads (30%), and scalp paresthesia (20%). The authors noted that temporary cessation of stimulation led to severe depression and severe anxiety. Suicide attempts were reported for 3 participants, only 1 of which was considered stimulation-related. The authors concluded that their findings provided evidence of significant benefit of DBS of the vALIC for treatment resistant OCD. However, they commented that “future sham-controlled trials should be conducted to provide further evidence that the effects of DBS for OCD extend beyond placebo effect.”

Garnaat (2014) reported a study assessing the size of the population of potential participants who may qualify for DBS for OCD. Using baseline data from the Brown Longitudinal Obsessive-Compulsive Study (BLOCS), which involved data from 325 treatment seeking participants, the authors used the inclusion and exclusion criteria from a study of DBS for OCD (ClinicalTrials.gov Identifier: NCT00640133) to determine how many BLOCS participants would have qualified for DBS. Using a Y-BOCS minimum threshold of 28, they reported that only 19% of participants still qualified, and this number further decreased to 17% when a functional impairment criterion was applied (GAF of at least 45). The pool of eligible participants shrank to 0.6% (n=2) when the rest of the inclusion criteria were applied including failure of both pharmacotherapy and CBT. Once exclusion criteria were applied, none of the participants qualified for DBS.

Across all the above cited studies, severity of OCD symptoms was measured with the Y-BOCS tool. The threshold for study inclusion ranged from a lower limit of 24 (Abelson, 2002) to a high of 31 (Tyagi, 2019). A study published by Mancebo (2008) investigating the correlates of OCD with occupational disability concluded that the most powerful predictor of occupational disability was the severity of OCD. Specifically, their results “indicated that with each standard deviation increase on the Y-BOCS (5.83 points), the odds of occupational disability increased by a factor of 2.26.” They reported that the average Y-BOCS score for occupationally disabled individuals was 26.53.

In 2021, the Congress of Neurological Surgeons (Staudt, 2021) published an update to the 2014 systematic review and evidence-based guidelines for DBS for obsessive-compulsive disorder (Hamani, 2014). Their analysis indicated that there was Level I evidence, based on Mallet and colleagues (2008) discussed above, supporting the use of bilateral subthalamic nucleus DBS for the treatment of medically refractory OCD. These are their recommendations:

• It is recommended that clinicians utilize bilateral subthalamic nucleus DBS over best medical management for the treatment of patients with medically refractory OCD (Level I).
• Clinicians may use bilateral nucleus accumbens or bed nucleus of stria terminalis DBS for the treatment of patients with medically refractory OCD (Level II).

There is insufficient evidence to make a recommendation for the identification of the most effective target.

The available evidence addressing DBS for OCD, while limited to trials with modest populations and methods, shows that this treatment can provide significant benefits for a prudently selected population of severely affected individuals with refractory OCD. The available studies have included extensive inclusion and exclusion criteria to assure that this treatment has been used only for individuals most likely to benefit, least likely to suffer from adverse events, and for whom all other less invasive options have been attempted and failed. Additional research is needed in the currently excluded population to determine safety and efficacy of this treatment. While there remains substantial risk of adverse events, the demonstrated improvements in the severity of OCD symptoms may warrant selection of this treatment option for individuals with severe functional impairment and the absence of contraindications (see exclusion criteria below).

The exclusion criteria from representative case series and clinical trials investigating DBS for OCD are summarized in the table below:

In 2025, Abdulbaki and colleagues conducted an umbrella review of 7 prior meta-analyses which included 29 studies evaluating DBS for OCD. DBS was associated with significant improvements in OCD severity (Y-BOCS mean difference=14.12 points; p<0.00001) and associated anxiety (HAM-A=10.71; p<0.00001), depression (HAM-D=11.14; p<0.00001), and global functioning (GAF=5.20; p<0.00001). The authors noted limited randomized evidence and heterogeneity across studies, supporting DBS efficacy while highlighting the need for additional rigorous trials.

In 2025, Cohen and colleagues conducted an individual-participant meta-analysis of sham-controlled DBS randomized trials for refractory OCD (9 trials; n=91) and found a mean 5.1-point Y-BOCS reduction favoring active DBS over sham, with an odds ratio (OR) of 4.7 for ≥ 35% response (95% confidence interval [CI], 1.8-12.2). Certainty of evidence was considered low due to limited samples, heterogeneity, and trial design limitations. Reported adverse events included hypomania and cognitive effects.

Deep Brain Stimulation (DBS) for Epilepsy

DBS has been proposed as a treatment for medically refractory epilepsy that persists in severity and/or frequency despite a reasonable trial of two or more antiepileptic medications, as an alternative to resective surgery and when cortical stimulation is not appropriate.

Results from the large-scale Stimulation of the Anterior Nuclei of Thalamus for Epilepsy (SANTE) trial, a double-blind RCT of DBS for epilepsy, were reported by Fisher (2010). This study used a standard DBS device (Medtronic Mode 3387) stimulating the anterior nuclei. All participants underwent DBS implantation followed by 3 months of randomized and blinded active stimulation (n=54) or no stimulation (n=55), then followed by 9 months of active stimulation for all participants. A total of 110 participants had DBS electrode implantation. One participant in the active group was not included in the data analysis and no explanation for this was provided in the article. Both the active and control groups demonstrated significant decreases in seizure activity through the blinded period. However, the control group trended towards baseline levels at the end of the third month. The active group had a sustained and significant decrease in seizure activity (p=0.0017). A statistically significant difference between groups was only seen in the third month, in favor of the stimulation group (p=0.0023). Changes in additional outcome measures did not show significant differences between groups. During the blinded phase, the frequency of complex partial seizures improved more in the stimulation group vs. controls (p=0.041). Additionally, seizure-related injuries occurred more in controls vs. stimulated participants (26% vs. 7%; p=0.01). No differences were noted in participants with prior treatment of vagus nerve stimulation. At completion of the blinded phase, 108 (98.1%) participants entered the open-label phase. The median seizure frequency percent change from baseline for participants with at least 70 diary days prior to the visit was -41% (n=99) at 13 months and -56% (n=81) at 25 months. The 50% responder rate at 13, 25, and 37 months was 43%, 54% and 67%. Through 13 months, 808 adverse events were reported in 109 participants; 55 events were categorized as serious and 238 were considered device-related. The most common device-related events were paresthesias (18.2%), implant site pain (10.9%), and implant site infection (9.1%). Five deaths were reported in the follow-up period, including 3 from sudden unexplained death in epilepsy (SUDEP), 1 participant from unobserved drowning in a bathtub, and 1 suicide. None of the deaths were judged device-related by center investigators. During the blinded phase, the stimulation group reported more adverse events relating to depression (8 vs. 1) and memory impairment (7 vs. 1). Participants in the stimulation group experienced fewer seizure-related injuries (7.4%) vs. the control group (25.5%, p=0.01). The authors state that DBS of the anterior nuclei in this population was mostly palliative in nature, but 14 participants (12.7%) became seizure-free for at least 6 months. Additionally, significant benefits were seen in some participants who were not previously helped by multiple drugs, vagus nerve stimulation (VNS), or epilepsy surgery. Finally, they conclude by stating, “Additional clinical experience may help to establish the best candidates and stimulation parameters, and to further refine the risk-benefit ratio of this treatment.” This is especially true considering the significantly increased rate of depression-related adverse events reported in the experimental group. It must be noted that this study only followed 13 participants past 13 months, mitigating the utility as well as impact of the longer-term data presented.

Salanova and others published a long-term follow-up study of the SANTE trial in 2015. Beginning 13 months following device implantation, 105 participants receiving active stimulation were followed for an additional 4 years. The authors reported that for participants with at least 70 diary entries recorded at 1 year (n=99), median change for seizure frequency from baseline decreased by 41% (p<0.001), and by 69% at 5 years (n=59; p<0.001). For the same population, reduction in the most severe type of seizure was 39% at 1 year (p<0.001) and 75% at 5 years (p<0.001). During the 5-year study, 17 of 109 participants (16%) reported a 6-month seizure-free interval. A 2-year seizure-free interval was reported for 6 of 109 participants (5.5%). Mean improvement in the Liverpool Seizure Severity Score (LSSS) was 13.4 at 1 year and 18.3 at 5 years (p<0.001 for both). Similarly, results from the Quality of Life in Epilepsy-31 (QOLIE-31) tool improved from baseline by 5.0 points at 1 year and 6.1 points at 5 years (p<0.001 for both). A change of 5 points on this measure is considered clinically significant, and was experienced by 46% and 48% of participants at 1 and 5 years. Overall, 39 of the 110 participants (35.5%) experienced some device-related serious adverse events, which predominantly occurred within the first months of implantation. The most common were impact site infection in 10% of participants and leads not within target area (8.2%). Depression was reported in 32.7% of participants over 5 years, but only 3 were considered device-related. Memory impairment was reported in 25.5% of participants. SUDEP was reported in 7 participants over the 5-year study period, but none were considered device-related by the data monitoring committee. This study demonstrates significant long-term benefit from DBS for individuals with epilepsy, however, this was a relatively small and unblinded study. Further data from larger blinded RCTs are warranted.

Another study using data from the SANTE trial reported on memory and mood outcomes (Tröster, 2017). Neuropsychological assessments were taken at multiple time points throughout the trial, including baseline, 4 weeks, 4 months, 7 months, 13 months, and yearly up to 7 years (n=67, 61% of the original study cohort). During the blinded phase, depression was reported in 14.8% of active group participants vs. 1.8% of control group participants (p<0.016), and adverse memory events were reported in 13.0% of active group participants vs. 1.8% of control group participants (p=0.032). For participants with depression, 72% had reported prior depression, and 23% experienced new depression symptoms. In participants with adverse memory events in the blinded phase, prior visual memory events were reported in half of participants who reported having visual memory events and 37.5% of participants reported experiencing verbal memory events had prior verbal memory events. Interestingly, while 66% of participants reporting depression in the active group had a prior history of depression diagnoses, none of these participants complained of depression during the baseline observation period or unblinded phase. Likewise, none of the participants reporting memory events experienced them outside of the blinded phase. Also, during the blinded phase, presence of a “confusional state” was reported in 7.4% of active group participants vs. 0% of control group participants and “anxiety” was reported in 9.3% of active group participants vs. 1.8% of control group participants, but none of these comparisons were statistically significant. The authors concluded that prior depression diagnosis might heighten risk of a depression adverse event within 4 months of surgery, but those without presurgical memory impairment may be more at risk for experiencing memory adverse events. Additionally, for the cohort followed for the full 7 years, they report no significant cognitive declines, neurobehavioral problems (for example, apathy, disinhibition), subjective cognitive declines, or affective distress (depressive and anxious symptoms).

Based on the SANTE trial data, the FDA granted pre-market approval on April 27, 2018 to the Medtronic DBS Therapy System for the treatment of epilepsy with bilateral stimulation of the anterior nucleus of the thalamus (ANT) as an adjunctive therapy for reducing the frequency of seizures in individuals 18 years of age or older diagnosed with epilepsy characterized by partial-onset seizures, with or without secondary generalization, that are refractory to three or more antiepileptic medications. As noted above, the SANTE trial data has some significant methodological flaws, and the rates of depression and other adverse effects remain a concern.

In a meta-analysis by Meissner (2013) investigating the impact of sham vs. placebo treatments in studies of DBS for epilepsy, the authors reported that both sham surgical and acupuncture procedures provided significantly more placebo effect than oral placebo. They commented that clinicians need to remember that a relevant part of the overall effect they observe in practice might be due to nonspecific effects. This is apparently true for these studies in the short-term. However, in the Fisher study, the placebo/sham effect mostly disappeared by the end of the 3-month blinded phase in the control groups.

In 2018 Järvenpää published a report of psychiatric adverse events in a series of 22 participants treated with DBS. Of the 22 participants, 4 were reported to have had significant mood or psychiatric adverse events, 2 with prior history of depression and 2 without. The onset of adverse events varied considerably, occurring at 2 days through 5 years after active stimulation was initiated. The authors reported that in the 3 participants with no prior history of mood or psychiatric conditions, altering DMS treatment parameters completely alleviated the symptoms. In the fourth participant, who had a prior history of depression and aggression, symptoms were decreased with parameter adjustments and medical management, but were not completely resolved. All 4 participants experienced significant decreases in seizure activity throughout their treatment, with sustained benefit following adverse event-related adjustments. This study indicates that while mood and psychiatric adverse events are a concern with DBS treatment for epilepsy, with proper monitoring and management they can be alleviated or significantly reduced.

Herman and colleagues (2019) reported the results of another small double-blinded RCT investigating the safety and efficacy of DBS in 18 participants suffering from focal, pharmacoresistant epilepsy. Participants were assigned to either active or sham treatment. The duration of this trial was 12 months, but participants were provided their randomized treatment only for the first 6 months. All participants received active treatment for the second 6-month period. The authors reported no significant differences between groups at the end of the blinded 6-month period. During the open active compared to treatment phase at 6-12 months, there was a significant 22% reduction in the frequency of all seizures vs. baseline (p=0.009). Four participants had ≥ 50% reduction in total seizure frequency, and 5 participants had a ≥ 50% reduction in focal seizures at the 12-month time point. No increased effect over time was shown. LSSS at 6 months showed no significant difference between groups, but a small, significant reduction in LSSS was found when all participants had received stimulation for 6 months.

In 2019, Yan and colleagues performed a systematic review of DBS for drug-resistant epilepsy (DRE) in pediatric participants. The review included 21 studies with 40 pediatric participants identified (4-18 years old). The follow-up period varied widely. There was no upper limit given, but the authors stated that a majority of the participants had a follow-up period of at least 18 months, but some participants only had 2 weeks of follow-up. The treatment areas also varied, with electrodes placed in the bilateral or unilateral centromedian nucleus of the thalamus, bilateral anterior thalamic nucleus, bilateral and unilateral hippocampus, bilateral and unilateral STN, bilateral posteromedial hypothalamus, unilateral mammillothalamic, and caudal zona incerta areas. The authors concluded that 85% of the participants (34 out of 40) had a reduction in seizure frequency. No site-specific analysis was provided to allow understanding of the benefits or harms of any specific stimulation site. The authors also noted that complications specific to pediatric participants were not thoroughly analyzed or synthesized, and that long-term complications of this treatment in pediatric participants are not yet understood.

A systematic review and meta-analysis done by Vetkas (2022) concluded DBS of the anterior thalamic nucleus is the most appropriate treatment area for DRE based on current evidence. This analysis included 44 studies of DBS for DRE on the anterior thalamic nucleus, centromedian thalamic nucleus (CMT), and hippocampus and included 527 participants. The authors concluded that “the best evidence exists for DBS of the anterior thalamic nucleus” and “further randomized trials are required to clarify the role of CMT and hippocampal stimulation.” Sobstyl and colleagues (2024) arrived at a similar conclusion in their systematic reviews on the anterior nucleus and centromedian nucleus of the thalamus and hippocampus as did Verly and colleagues (2024).

Peltola and colleagues (2023) reported a study investigating DBS of the anterior nucleus of the thalamus for treatment of DRE using data from the Medtronic Registry for Epilepsy (MORE) multicenter registry. A total of 191 participants were recruited but after eligibility was reviewed, 170 participants were implanted with a DBS device. Participants were at least 18 years old (mean age was 35.6 years old), had DBS for DRE, and were followed for at least 24 months. Outcomes measured included responder rate, seizure frequency, adverse events, and incidence of depression. At 2 years, the responder rate was 32.3% and the median monthly seizure frequency was reported to have decreased by 33.1% (p<0.0001). There was a subgroup of 47 participants who completed 5 years of follow-up, with a responder rate of 53.2%. The median monthly seizure frequency for this group was reported to have decreased by 55.1% (p<0.0001). Adverse events included changes in seizures, memory impairment, depressive mood, epilepsy, headache, head injury, irritability, anxiety, and cognitive impairment. There was one death from definite sudden unexpected death in epilepsy. The authors concluded that the MORE registry supports the safety and effectiveness of DBS of the anterior nucleus of the thalamus for DRE. Kaufmann and colleagues (2024) conducted a similar long-term evaluation of participants in the MORE registry and arrived at a similar conclusion.

While the available published peer-reviewed evidence addressing the use of DBS for epilepsy is limited mostly to the SANTE trial results, use of this treatment approach has continued, and clinical experience has been gained. As a result, there is a growing body of expert experience and opinion addressing the complications noted above, specifically the concerns regarding the incidence of SUDEP and depression. Expert opinion over the past decade has evolved to see SUDEP risk following DBS initiation as no greater than the SUDEP risk for individuals with medically refractory seizures. Similarly, the concerns regarding depression and mood disorders have been more clearly elucidated with the publication by Tröster and colleagues. With that evidence it has been made clear that specific populations may suffer additional risk of depression or mood disturbances with DBS treatment. However, in the clinical setting there must be an assessment of balancing the risks due to insufficiently treated epilepsy vs. the risks associated with depression and mood disturbances, and the predominant current consensus is that the risks posed by insufficiently treated epilepsy are greater. In summary, the population with medically refractory epilepsy for whom DBS has been proposed suffer from significant morbidity and mortality unrelieved by medical therapy. While some may be candidates for cortical stimulation, many are not. Additionally, resective surgical procedures may be an available option for some, but the use of less invasive and irreversible approaches should be made available. Of note, there are no devices approved by the FDA for use in individuals younger than 18 years of age (American Association of Neurological Surgeons Congress [AANS], 2024).

In 2023, Fields and colleagues reported results of a multicenter retrospective study of seven U.S. epilepsy centers evaluating thalamic responsive neurostimulation in drug-resistant epilepsy. A total of 25 individuals received unilateral or bilateral leads in the anterior or centromedian thalamic nuclei and were followed for ≥ 6 months. Median seizure reduction improved over time: 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% beyond 2 years. A total of 9 individuals experienced seizure-free intervals longer than 3 months, most had no change in antiseizure medications, and 88% showed improvement on a global clinical impression scale. Safety signals were limited to 2 serious events (1 asystole likely seizure-related; 1 asymptomatic intraventricular hemorrhage at implant). Limitations included the retrospective design, heterogeneous indications and targets, reliance on self-report, and frequent concomitant non-thalamic leads that may confound results.

In 2024, Bahadori and colleagues conducted a PRISMA-guided systematic review and meta-analysis of DBS for drug-resistant epilepsy. A total of 54 studies were included (38 meta-analyses; n=999). Seizure frequency decreased significantly (standardized mean difference [SMD] 0.609; p<0.001) and quality of life improved (SMD -0.442; p<0.001). Benefits were reported across anterior thalamic, centromedian, hippocampal, and subthalamic targets, with larger effects in hippocampal series. Greater efficacy was seen with follow-up of 2 years or longer. Reported adverse events were uncommon and typically transient. Certainty is limited by heterogeneity and the predominance of nonrandomized designs.

In 2024, Yassin and colleagues published a PRISMA-guided systematic review with individual-participant meta-analysis of DBS for drug-resistant epilepsy, aggregating 39 studies (n=296) across 3 targets: anterior nucleus of thalamus (69% of participants), hippocampus (11% of participants), and centromedian nucleus (21% of participants). The ‘≥ 50% responder rate’ was 70.6% overall; response was higher for individuals experiencing generalized versus focal seizures (93.2% vs 63.9%). By target, responder rates were 83.9% for centromedian nucleus, 77.4% for hippocampus, and 65.5% for anterior nucleus of thalamus. Longer therapeutic windows independently predicted response. Complications were infrequently reported. Limitations included limited sample sizes for the hippocampus and centromedian cohorts, heterogeneity, and variable follow-up.

In 2025, Dhaliwal and colleagues published a systematic review and meta-analysis of thalamic DBS for drug-resistant epilepsy. A total of 49 articles were included (n=1125) and outcomes were assessed at a minimum of 12 months. Targets included the anterior nucleus, centromedian nucleus, and pulvinar. The pooled mean seizure reduction was 62.3% across studies (p<0.01). Target-specific estimates were 64.3% for the anterior nucleus and 69.1% for the centromedian nucleus; data were insufficient for inclusion of pulvinar data in the meta-analysis. Responder rates (≥50% reduction) were 61.5% for anterior nucleus and 69.1% for centromedian nucleus. Seizure freedom was uncommon (3% anterior nucleus; 1% centromedian nucleus). Longer follow-up (> 24 months) was associated with higher response, particularly for anterior nucleus. Risk of bias was mainly from nonrandomized designs, although sensitivity analyses were consistent and no strong publication bias signal was detected.

Deep Brain Stimulation (DBS) for Other Conditions

Tye and colleagues (2009) investigated the effectiveness of DBS in treatment-resistant depression, OCD, and Tourette syndrome (TS). The authors found that DBS treatment for TS was largely dependent upon electrode placement. One small study (n=5) found that bilateral thalamic electrode placement reduces tic frequency and severity in refractory TS (Maciunas, 2007). Other DBS electrode implantation targets for TS include the centromedian thalamic region (Okun, 2012; Servello, 2008) and the globus pallidus (Diederich, 2005).

In 2009, Porta reported the findings of a case series study involving 18 participants who underwent bilateral thalamic DBS for TS. At the 24-month follow-up point, there was a marked reduction in tic severity (p=0.001), improvement in obsessive-compulsive symptoms (p=0.009), anxiety symptoms (p=0.001), depressive symptoms (p=0.001), and subjective perception of social functioning/quality of life (p=0.002) in 15 of 18 participants. There were no substantial differences on measures of cognitive functions before and after DBS. The authors concluded by stating, “Controlled studies on larger cohorts with blinded protocols are needed to verify that this procedure is effective and safe for selected patients with TS.”

Ackermans and colleagues (2011) noted that since 1999, 10 different brain areas have been described as a target for DBS in Tourette syndrome. They conducted a study of 8 individuals in a double-blind, randomized cross-over trial using reduction of tic severity as the primary outcome. After surgery, the participants were randomly assigned to 3 months stimulation followed by 3 months OFF stimulation (Group A) or vice versa (Group B). The cross-over period was followed by 6 months ON stimulation. Tic severity during ON stimulation was significantly lower than during OFF stimulation, with substantial improvement (37%) on the Yale Global Tic Severity Scale (YGTSS) (mean 41.1 ± 5.4 versus 25.6 ± 12.8; p=0.046). The authors concluded that these preliminary findings suggest efficacy of DBS for tic symptoms in TS; however, further RCTs on other targets are urgently needed since the optimal DBS target for TS is still unknown.

Welter (2017) published the results of a double-blind RCT involving 17 participants with severe medically refractory Tourette syndrome who were treated with bilateral implantation of a deep brain stimulator with electrodes to the anterior globus pallidus. Participants were randomly assigned in a 1:1 fashion to either active (n=8) or sham stimulation (n=9). At 2 months following implantation, all participants had their stimulators activated to determine the study settings. One month later participants were randomized to their treatment group and followed in a blinded fashion for an additional 3 months. After that period, all participants had their devices activated in an open-label fashion for an additional 6 months. Medication regimens were continued during the study. A total of 16 participants completed the double-blind study period. The authors reported no significant differences between groups at 3 months regarding YGTSS scores (p=1.0). During the open-label phase, YGTSS scores improved significantly in all participants (p=0.23). Improvement of 25% or more in YGTSS scores from baseline to the end of the open-label phase was noted in 12 of the 16 completing participants (p=0.0017). At the end of the open-label phase the stimulators were turned off for 72 hours, at which time mean YGTSS scores decreased 75.7% (p=0.02). During the blinded phase, no significant differences were noted between groups regarding motor or vocal tic YGTSS subscales or any other measures. Between baseline and the end of the open-label phase, significant differences in the motor and vocal tic YGTSS subscales, the Rush Video Rating Scale (RVRS), GAF, the MADRS, and Hospital Anxiety and Depression Scale (HADS) (anxiety), but not in CGI, the Brief Anxiety Scale (BAS), the HADS (depression), the Y-BOCS, the Stroop interference index, Social Adjustment Scale Self- Reported (SAS-SR), or SF-36 scores. A total of 15 serious adverse events were reported in 13 (68%) participants, including infections leading to removal of the stimulator and electrodes in 4 (21%) participants. Transient headaches (n=5) and pain along the scars (n=2) were also reported. Adverse events related to stimulation across both groups were reported in 17 participants, including increased tic severity and anxiety, depressive symptoms, dysarthria, sleep disorder, and imbalance or abnormal movements resembling dyskinesia that resolved rapidly after stimulator adjustments. The authors concluded that 3 months of DBS is insufficient to decrease tic severity for individuals with Tourette syndrome and further study was needed. Also in 2017, Martinez-Ramirez and colleagues reported an analysis of data from 185 participants with Tourette syndrome included in the prospectively collected International Deep Brain Stimulation Database and Registry who were treated with bilateral DBS. Surgical selection was made using local evaluations and recommendations, with no standardized inclusion or exclusion criteria. Location of electrodes was likewise not standardized, with stimulation occurring at the centromedian thalamic region (n=93), anterior globus pallidus internus (n=41), posterior globus pallidus internus (n=25), and anterior limb of internal capsule (n=4). The authors reported that the mean total YGTSS score improved from 75.01 at baseline to 41.19 at 1 year (p<0.001). The mean motor tic subscore improved from 21.00 at baseline to 12.91 after 1 year (p<0.001), and the mean phonic tic subscore improved from 16.82 at baseline to 9.63 at 1 year (p<0.001). The adverse event rate was 35.4% (56 of 158 participants), with reports of intracranial hemorrhage (n=2), infection (n=5), and lead explantation (n=1). The most common stimulation-induced adverse effects were dysarthria (n=10) and paresthesia (n=13). The authors concluded that DBS was associated with symptomatic improvement in individuals with Tourette syndrome, but also with important adverse events.

The European Clinical Guidelines for Tourette Syndrome and Other Tic Disorders. Part IV: Deep Brain Stimulation (Müller-Vahl, 2011) stated that:

…Of the 63 patients reported so far in the literature 59 had a beneficial outcome following DBS with moderate to marked tic improvement. However, randomized controlled studies including a larger number of patients are still lacking. At present time, DBS in TS is still in its infancy.
…However, among the European Society for the Study of Tourette Syndrome (ESSTS) working group on DBS in TS, there is general agreement that, at present time, DBS should only be used in adult, treatment resistant, and severely affected patients. It is highly recommended to perform DBS in the context of controlled trials.

Additional uses for DBS are being investigated. For example, in psychosurgery there has been a shift of interest away from ablative techniques and toward DBS. However, most studies of DBS for depression and anorexia are few and involve small numbers of participants (Bergfeld, 2016; Lipsman, 2013, Sachdev, 2009; Schlaepfer, 2013; Wu, 2013). Patel and colleagues (2011) reported a case study using DBS for treatment of severe, refractory hypertension. In 2011, the National Institute for Health and Clinical Excellence (NICE) published DBS assessments in the treatment of trigeminal neuralgia and chronic pain syndromes. They found that the available evidence does not support this use.

In 2015, Dougherty and colleagues published the results of a 24-month sham-controlled RCT involving 30 participants with treatment resistant depression treated with DBS or sham DBS (n=15 per group). The authors reported no significant differences in response rate between groups (20% vs. 14.3%, respectively). Results from the MADRS demonstrated no significant differences throughout the 16-week controlled phase of the trial. In 2017 a larger 6-month sham-controlled RCT involving 90 participants was published by Holtzheimer and others. As with the prior study, no statistically significant difference in response was reported (20% in the active group vs. 17% in the sham group). Serious adverse events were experienced by 28 participants (40 events total), with 8 deemed to be related to the study device or surgery. The findings of these studies demonstrated no benefit to DBS for treatment resistant depression.

DBS is also being studied as a treatment for tremors from other causes including, but not limited to, multiple sclerosis (MS), tardive dyskinesia, trauma, and degenerative disorders. In addition, DBS is being investigated to determine if functional improvement is achieved and maintained for other conditions such as chronic cluster headache, cerebral palsy, substance use disorder, and TS.

Responsive Neurostimulation (RNS)

The RNS^® System (NeuroPace, Inc., Mountain View, CA) consists of a cranially implanted, programmable cortical neurostimulator that senses and records brain activity through electrode-containing leads that are placed at the seizure focus. The device provides what the manufacturer refers to as “responsive cortical stimulation,” which senses and records seizure activity and responds according to a pre-set program. The system is intended to reduce the frequency of seizures in individuals with medically refractory epilepsy that persists in severity and/or frequency despite a reasonable trial of two or more antiepileptic medications. On November 14, 2013, the RNS System was approved through the PMA process by the FDA with the following indication:

…as 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.

The RNS system was approved on the basis of data from three trials; an initial Feasibility study, the Pivotal Trial, and the Long Term Treatment investigation trial (LTT). In the Feasibility study, the initial 4 participants were involved in an open-label protocol. The subsequent 61 participants were enrolled in a double-blind RCT in which participants received active or sham treatments. The results of this study have been presented in conjunction with the results of the other two studies in the summary of safety and effectiveness data presented to the FDA, but have not been reported separately in a peer-reviewed published paper. In the absence of a standalone peer-reviewed publication, the Feasibility study cannot be independently evaluated for methodological rigor, and its findings are insufficient to support conclusions in isolation.

RNS Pivotal Trial

The pivotal trial evaluating responsive cortical stimulation (RNS system) was a multicenter, randomized, double-blind, sham-controlled study involving 240 enrolled individuals, of whom 191 underwent implantation and were included in the analysis (Bergley 2015; Heck 2014; Morrell, 2011; Nair 2020). Eligible participants were 18 to 70 years of age with partial-onset seizures refractory to two or more antiepileptic medications, experiencing an average of three or more disabling seizures per month, and with one or two epileptogenic foci localized by diagnostic testing. Following implantation and a postoperative stabilization period, participants were randomized to active or sham stimulation and followed through a 12-week blinded evaluation period, after which all participants received active stimulation in an open-label extension.

During the blinded phase, seizure frequency was reduced by 37.9% in the treatment group compared to 17.3% in the sham group (p=0.012), demonstrating a statistically significant treatment effect. However, responder rates (≥ 50% reduction in seizures) were similar between groups (29% vs. 27%), and both groups experienced an initial post-implant reduction in seizures, suggesting a potential implantation or placebo effect.

In the open-label phase, seizure reductions were sustained and appeared to improve over time. Heck et al. (2014) reported median seizure reductions of 44% at 1 year and 53% at 2 years (p<0.0001), with approximately half of participants achieving a ≥ 50% reduction in seizures. There were no adverse effects on neuropsychological function or mood, and adverse event rates were consistent with those expected for implanted neurostimulation devices.

Long Term Treatment investigation trial (LTT)

Subsequent long-term follow-up studies extended these findings but were limited to uncontrolled observational data. Bergey et al. (2015) reported median seizure reductions ranging from 48% to 66% over years 3 through 6, with sustained improvements in quality of life and device-related adverse events including implant-site infection (9.0%) and explantation (4.7%) over a mean follow-up of 5.4 years. Data at this stage demonstrated relatively stable responder rates of approximately 56-61% through years 3-6, suggesting persistence of effect but without a comparator group.

Nair et al. (2020) reported 9-year follow-up data from the same cohort, showing a median seizure reduction of 75% and a responder rate of 73%, with 35% of participants achieving ≥ 90% seizure reduction and approximately 18% experiencing at least 1 year of seizure freedom. Quality of life improvements were maintained, and no new safety concerns were identified. However, these results were derived from an open-label extension study and are subject to potential biases, including selection effects, changes in concomitant therapies, and lack of a control group.

The RNS System’s pivotal trial and LTT program had several strengths, including a randomized, sham-controlled design in the initial phase, multicenter participation, and relatively large sample size for a neuromodulation study. However, important limitations affect interpretation. The blinded phase was limited to 12 weeks, and all longer-term outcomes are derived from open-label follow-up without a comparator, introducing the potential for placebo effects, regression to the mean, and other sources of bias. In addition, adjustments in antiepileptic drug therapy were permitted during long-term follow-up, which may confound assessment of treatment effect. The similar responder rates observed during the blinded phase raise questions regarding the clinical magnitude of benefit despite statistically significant reductions in seizure frequency.

Overall, the pivotal trial demonstrates that responsive cortical stimulation is associated with a statistically significant short-term reduction in seizure frequency compared to sham stimulation. Longer-term observational data suggest that seizure reduction may be sustained and may improve over time in some individuals. However, the clinical significance of the treatment effect is modest in the controlled phase, and the durability of benefit is uncertain due to the lack of controlled long-term data. These findings support the use of responsive cortical stimulation as an adjunctive treatment option in carefully selected individuals with medically refractory focal epilepsy, while also supporting continued classification of the evidence for long-term efficacy as limited and observational.

Several post hoc analyses of the RNS clinical trial program, including the feasibility, pivotal, and long-term treatment (LTT) studies, have provided additional insight into outcomes in specific epilepsy subtypes. These analyses are particularly informative for individuals with mesial temporal and neocortical epilepsy who are not optimal candidates for resective surgery, helping to better define the role of responsive cortical stimulation in these populations

Use of the RNS system for the treatment of mesial temporal lobe (MTL) epilepsy was evaluated in a retrospective study involving data from 111 participants who were involved in the RNS feasibility (n=16), pivotal (n=95), and LTT studies (n=92) Geller, 2017). The mean follow-up at the time of data cutoff was 6.1 ± 2.2 years. Participants had one to four leads placed during the initial procedure, with one lead (n=1), two leads (n=92), three leads (n=4) or four leads placed (n=14). Only depth leads were placed in 76 participants, 29 had both depth and strip leads, and 6 had only strip leads. Disabling seizures were reduced by a median 66.5% at 6 years, and the 50% responder rate reached 64.6%. No seizures were reported by 20.8% of participants in the last 3 months. Over the open-label period, 45% of participants reported seizure-free intervals lasting ≥ 3 months, 29% lasting ≥ 6 months, and 15% lasting ≥ 1 year. There was no difference in seizure reduction in participants with and without mesial temporal sclerosis (MTS, p=0.42), bilateral MTL onsets (p=0.97), prior resection (p=0.54), prior intracranial monitoring, and prior VNS (p=0.78). The most common device-related serious adverse events were implant-site infection and device lead damage.  Lead replacement due to lead damage occurred in 7 participants. Three participants had a serious AE related to intracranial hemorrhage, and 2 were categorized as device related. A total of 6 deaths were reported, 1 suicide and 5 attributed to possible (n=2), probable (n=1), or definite (n=2) SUDEP. Other adverse events reported include photopsia (n=16), memory impairment (n=7), and depression (n=2). This analysis includes a relatively large cohort of individuals with mesial temporal lobe epilepsy and provides long-term follow-up, demonstrating sustained seizure reduction over time in a population that is often not a candidate for resective surgery. Outcomes were consistent across clinically relevant subgroups, including individuals with bilateral seizure onset, prior surgery, and prior VNS, supporting applicability to a heterogeneous, treatment-refractory population. However, this was a retrospective subgroup analysis of participants from prior clinical trials, and long-term outcomes were derived from an open-label phase without a concurrent control group. As such, results are subject to potential bias and cannot establish independent efficacy. The study was not powered for subgroup comparisons, and findings across clinical characteristics should be interpreted cautiously. In addition, the population overlaps with previously reported RNS cohorts, limiting its role as confirmatory evidence.

Jobst (2017) reported outcomes from 126 participants from the RNS pivotal (n=45) and LTT studies (n=81) with long-term follow-up. The mean follow-up at the time of data cutoff was 6.1 ± 2.6 years. Seizure data were available for 120 participants with > 1 year of follow-up, and 87 had at least 6 years of follow-up. The median percent reduction in seizures was 44% after 2 years, 61% after 5 years, and 76% after 6 years. During the open-label period, 37% of participants had at least one seizure-free interval lasting ≥ 3 months, 26% had at least one lasting ≥ 6 months, and 14% had at least one lasting ≥ 1 year. There were no statistically significant differences in seizure reduction based on previous surgery or VNS (p=0.12 and p=0.20, respectively). Both participants with and without structural lesions experienced a reduction in seizure frequency, and the reduction was greater in participants with a structural lesion than in those without (p=0.02). Serious adverse events related to intracranial hemorrhage were reported in 9 participants, with 6 attributed to seizure-related head trauma. Two participants had cerebral hemorrhages several years after implantation, with one considered device related. Serious infection-related adverse events were reported in 13 participants, with 9 resulting in explantation of the stimulator and 6 in explantation of the leads as well. Two participants developed scalp erosions over the neurostimulator. Death was reported for 5 participants with 1 suicide, 1 due to status epilepticus, 1 due to lymphoma, and 2 attributed to definite SUDEP. As with the paper reported by Geller above, this analysis was post-hoc, uncontrolled, and largely open-label, limiting causal inference. Results may have been influenced by selection bias, attrition, and concomitant medication adjustments, and seizure outcomes are based on participant-reported diaries, which may underestimate true seizure frequency.

Devinsky (2018) reported the results of a retrospective study investigating the incidence of SUDEP in 707 individuals implanted with the RNS system representing 2208 person-years of post-implantation follow-up data. This included 256 participants from the RNS clinical development program (feasibility, pivotal, and long-term treatment trials) as well as 451 individuals treated in the post-approval setting. The authors reported 14 deaths in the study cohort. The authors reported a SUDEP rate of 2.0/1000 patient stimulation years with an age-adjusted standardized mortality ratio (SMR) of 0.75 (95% CI, 0.27-1.65). Notably, 2 individuals classified as SUDEP were not receiving active stimulation at the time of death. The authors suggest that the observed SUDEP rate compares favorably with rates reported in other populations with treatment-resistant epilepsy. However, interpretation is limited by the observational design, small number of events, and wide confidence intervals, which preclude definitive conclusions regarding any reduction in SUDEP risk attributable to RNS therapy.

In 2020, Ma and colleagues reported the results of a multicenter retrospective cohort study of participants (n=30) with drug-resistant focal epilepsy and a regional neocortical seizure-onset zone (SOZ) delineated by intracranial monitoring who were treated with the RNS system for at least 6 months. The changes in seizure frequency were assessed relative to the preimplant baseline, and correlation between clinical outcome and stimulation parameters were evaluated. Participants’ ages ranged from 9 to 42 years, with mean duration of epilepsy of 14.2 ± 10.3 years, and a varied epilepsy etiology. There were 5 participants who underwent a partial resection of the SOZ concurrent with RNS system implantation. Median follow-up was 21.5 months. Median reduction in clinical seizure frequency was 75.5% (interquartile range 40% to 93.9%). There was no significant difference in outcome between participants treated with and without concurrent partial resection. Most participants were treated with low charge densities (1-2.5 µC/cm²). Seizure reduction was not correlated with interlead distance, maximum charge density, treatment duration, or concurrent partial resection. The study’s limitations include a modest sample size, retrospective design, heterogeneity of lead locations, and antiepileptic drug adjustments during the study period.

The RNS system has been demonstrated to be safe and effective in select adult individuals with partial onset seizures who have undergone diagnostic testing that localized no more than two epileptogenic foci, are refractory to two or more antiepileptic medications, and are currently having an average of three or more disabling seizures per month. Studies have shown significant improvements in seizure frequency.

RNS Therapy in Children and Adolescents

In 2020, Panov reported a retrospective, single-center study evaluating RNS treatment of 27 children and adolescents with DRE. The median age at the time of implantation was 14 years old (range 7-17 years) and 40.7% (11 of 27) had previous resective surgery with persisting seizures. Mean follow-up was 22 months, and 22 of the 27 participants were followed for at least 1 year. At 1 year, seizure frequency reductions were reported as follows: 11 (50%) participants had a 75%-100% reduction of seizures, 4 (18.2%) participants had a 50%-74% reduction of seizures, 5 (22.7%) participants had a 25%-49% reduction of seizures, and 2 (9.1%) participants had a 0%-24% reduction of seizures. There were no reports of postoperative hematoma, stroke, or RNS device malfunction in this study. Infections were reported in 3 (11.1%) participants; 1 participant required partial removal of the device and 1 participant required complete removal of the device. Interpretation of efficacy is limited by the uncontrolled design, as well as concurrent adjustments in antiseizure medications, which may have contributed to observed improvements. Additional limitations include the retrospective, single-center design, small sample size, relatively short follow-up, and potential selection bias toward more complex cases. Overall, this study provides preliminary evidence suggesting feasibility and an acceptable safety profile of RNS in pediatric individuals; however, the evidence is insufficient to establish efficacy or isolate the treatment effect.

In 2021, Nagahama reported a multicenter retrospective observational study of 35 individuals with childhood-onset DRE who were treated with the RNS device. The outcomes measured were reduction of disabling seizures and complications. The average follow-up was 1.7 years. Outcomes included reduction in disabling seizures and device-related complications. Among pediatric participants, 41% achieved ≥ 50% seizure reduction, including 24% with ≥ 90% reduction and 6% who were seizure-free, while 24% experienced no improvement. In the overall cohort, complications requiring surgical intervention occurred in 3 individuals (9%), all in the ≥ 18-year subgroup (2 infections and 1 lead fracture). No surgical complications were reported in the pediatric subgroup. Interpretation of these findings is limited by the retrospective design, small sample size, short and variable follow-up, and lack of a control group. Additional limitations include heterogeneity in participant selection and management, potential confounding from concurrent treatments, and reliance on non-standardized outcome assessment. While the results suggest that RNS may be feasible in carefully selected pediatric individuals, the evidence remains preliminary and insufficient to establish definitive conclusions regarding efficacy or long-term safety in this population.

In 2022, Kerezoudis published the results of a systematic review and patient-level meta-analysis of 8 studies involving 49 pediatric participants with epilepsy who received treatment with RNS. The median age was 15 years (range 7-17) and the median follow-up was 22 months (range 16-22). The most common location of implantation was the frontal lobe (27%), followed by mesial temporal structures (23%) and thalamus (17%). Bilateral implantation was performed in 38% of cases. Among participants with available follow-up data (n=44), the median seizure frequency reduction was 75% (inter quartile range [IQR] 50-88%) and 80% were classified as responders. In limited longitudinal data, 1 participant experienced a 50% reduction in seizures in the first 12 months followed by an increase in seizure frequency at 24 months. No neurological deficits were reported after the implantation, but hardware infections were mentioned in 4 cases (8%). Neurocognitive outcomes were described for 10 participants, with 8 having measurable improvement in school performance based on self- and parent reports. While this study reports substantial seizure reductions and acceptable short-term safety, the evidence base is limited by retrospective, uncontrolled designs, small sample size, heterogeneity, and significant risk of publication bias. The absence of randomized or comparative data precludes reliable attribution of benefit to the intervention. Overall, the evidence is very low quality and insufficient to establish effectiveness, supporting the need for controlled trials before routine clinical adoption.

In 2024, Levy and colleagues conducted a meta-analysis of the use of the RNS system among pediatric DRE individuals. They identified 15 relevant articles, yielding 98 participants in total. The median follow-up time was 12 months and the median percent seizure reduction at the final follow-up was 75% (n=82). About 18% (n=15) of those who reported seizure reductions were super-responders, meaning that their seizures reduced by at least 90% from the latest follow-up. Of the 27 individuals who attempted to reduce antiseizure medication (ASM), 6 (22%) were successful, and 94% (16 out of 17 cases) reported some degree of behavior improvement. The postoperative complication rate was 8.4%, with half of these being device-related infections. Some limitations include that this study was a retrospective pooled analysis, the lack of universal reporting across outcome measures, and limited statistical power given small sample sizes.

In 2023, Singh published the results from a multicenter observational study combining prospective registry data with retrospective analysis of 56 individuals under 18 years of age undergoing RNS placement through the Pediatric Epilepsy Research Consortium Surgery Registry. The mean age at baseline evaluation was 13.7 years (range 5.9-17 years) with a mean epilepsy duration of 8.1 years. The mean number of previously trialed antiseizure medications at baseline was 4.2 (range 1-15), and the average number of antiseizure medications taken at the time of presurgical evaluation was 2.5 (range, 1-5). RNS lead implantation varied and included a combination of depths and strips (n=18, 32%), depth electrodes only (n=25, 45%), or strip only (n=13, 23%). Twenty-one (38%) participants had more than two electrodes implanted. The remaining 35 participants had two leads implanted. Location of implantation included temporal only (n=18, 32%), extratemporal only (n=25, 45%), and a combination of extratemporal and temporal (n=13, 23%). Short-term follow-up was available for 55 of the 56 (98%) participants with a mean duration of 11.7 months, with 1 lost to follow-up. Surgical complications occurred in 3 (5%) participants, including 1 individual with a malpositioned lead and transient weakness and 2 who had transient weakness in relation to resection or subdural grid placement, not related to RNS placement. Of the 55 participants with data, 37 (67%) had a reported 50% seizure reduction. Four had been clinically seizure-free with RNS recording since implantation (2- to 12-month follow-up). One of those participants had resective surgery. For each of these 4 participants, stimulation remained off. Thus these 4 were not included in the secondary outcome analysis. Among the remaining 51 (83%), 33 (65%) were responders, with greater than 50% seizure reduction. This included 5 (10%) who were seizure-free at follow-up (mean 15.6 months; range, 5 to 27 months). The remaining 18 (35%) were nonresponders with less than 50% seizure reduction. No significant associations were identified between outcomes and age at implantation (p=0.2283), MRI findings (p=0.000), use of invasive EEG evaluation (p=1.000), the number of RNS electrodes implanted (p=1.000), location of seizure onset (p=0.6091) or the type of RNS implantation (strips, depths, or both; p=0.9405). Interpretation of these findings is limited by the uncontrolled observational design, short duration of follow-up, reliance on caregiver-reported seizure frequency, and potential confounding from concurrent treatments, including medication adjustments and prior or concomitant surgical interventions. While the results suggest that RNS may reduce seizure frequency in some pediatric individuals with DRE, the evidence remains preliminary.

In 2024, Enner published the results of a retrospective case series involving 14 individuals aged 6-19 years (range 4-19, mean 15.6) who underwent RNS for DRE. Two participants were over the age of 18, and 7 (50%) had had previous VNS or resective procedures. Follow-up ranged from 6 months to 4 years. One participant experienced a post-operative infection requiring RNS removal 2 months after implantation. No participants were reported to have worsening clinical seizure frequency at 6-months. Compared to the 1-month post-op evaluation, there was a statistically significant improvement (p=0.0268) in average long seizure episode occurrence at the most recent recorded visit (18.6 vs. 2.9). Overall decrease in seizure activity was not reported. The authors concluded that RNS is feasible and safe for individuals as young as 6 years old with DRE when appropriate seizure focus has been identified. Additionally, they noted that RNS may be used in conjunction with other surgical epilepsy treatment modalities and use of two RNS devices simultaneously is achievable “for patients with a broad epileptogenic network or multifocal seizure onset zones”. However, the small sample size, retrospective design, lack of a control group, heterogeneous population (including prior and concurrent surgical treatments), and reliance on surrogate and caregiver-reported outcomes are significant limitations. As such, the study provides preliminary evidence of feasibility and short-term safety but does not establish clinical effectiveness.

Mixed DBS and RNS Studies for Epilepsy

Singh (2025) reported a retrospective case series involving 54 participants aged 6-22 years old with DRE who underwent electrical simulator implantation with either DBS (n=24) or RNS (n=30). The RNS cohort participants ages were between 6 and 20 years. RNS was chosen for participants with focal eloquent-onset epilepsy and DBS was selected for individuals with multifocal, regional, generalized, or mixed epilepsy. The mean follow-up was 24.4 ± 15.3 months (median 21 months, range 6-69 months). In the RNS cohort, 90% of individuals only had depth electrodes, while 10% had a combination of depth and subdural strip electrodes. The authors reported that 1 RNS group participant experienced symptomatic noninfectious peri-electrode inflammation at 16 days postoperatively that resolved with explant. This adverse event was deemed unrelated to the device and attributed to pre-existing multiple sclerosis (MS). Six participants, 4 of whom were in the RNS group, experienced adverse events, 3 requiring additional surgery for infection (n=1), wound dehiscence (n=1), and the aforementioned pre-electrode inflammation, The remaining participant experienced a pseudomeningocele with possible CSF leak. Explantation was required in the infection and MS cases. No significant association between adverse events and the device type was found (p>0.9999). In the cohort less than 18 years of age, 4 of 37 (10.8%) participants had postoperative wound complications, 3 (8.1%) returned to surgery, 2 (5.4%) required explant, and 1 (2.7%) had an SSI. The authors reported that these rates were not significantly different than the rates in the entire cohort. No adverse events related to hemorrhage on CT or MRI, malpositioned electrodes, lead or wire fractures, device malfunction, or hydrocephalus were reported. A transient increase in seizures the week following surgery was reported in 4 (7.4%) participants treated with RNS. One individual died of SUDEP at 28 months after RNS placement, with recordings demonstrating a seizure shortly before death occurred. Seizure frequency was determined through individual and family reporting. At 6 months postoperatively, the overall responder rate (≥ 50% reduction in seizure frequency) was 33% for the RNS group and 50% for the DBS cohort. There was no loss to follow-up at this time point. At 12 months, the overall responder rate increased to 54% for the RNS group and 73% for the DBS cohort with 87% (26/30) of RNS participants and 92% (22/24) of DBS participants reported. Increased seizure frequency at 6 months postimplant occurred in 1 RNS participant and 2 participants treated with DBS.

Kuo (2026) reported on the safety of RNS and DBS in a retrospective single-center case series involving 217 individuals with DRE treated with DBS or RNS. The report included results from 14 children, 43 adolescents, 160 adults. Two-lead DBS was done in 111 (51%) participants, 4-lead DBS in 51 (23.5%), and RNS in 55 (25.3%). A total of 182 participants had at least 1 year of follow-up after implantation. The mean age at implantation was 29.7 years (range 4 to 77.3), with a mean follow-up of 4.1 years (range 0.3 to 20 years). Focal epilepsy accounted for 78.3% of cases, mixed generalized and multifocal epilepsy was reported in 14.3% and generalized epilepsy in 7.4%. The distribution of epilepsy types (p=0.002) and device types (p=0.013) differed significantly among children, adolescents, and adults. Focal epilepsy was more common among adults compared to children and adolescents (81.9% vs. 50% and 74.4%, respectively). For device type, RNS was used in no children and 23.3% and 28.1% of adolescent and adult participants, respectively. DBS with 4-leads was used most frequently in 57.1% of children and 27.9% and 19.4% of adolescents and adults. DBS with 2-leads was used in approximately equal numbers across groups (42.9%, 48.8% and 52.3%, respectively). Device-related adverse events occurred in 23% of participants, including stimulation-related paresthesia (7.8%), infection (4.1%), asymptomatic intracranial hemorrhage (ICH) (3.7%), bowstring effect (extension wire tethering that limits neck mobility, 3.2%), operation-related focal weakness (2.3%), wound dehiscence (1.8%), generator migration (1.8%), lead malposition (1.4%), lead fracture (1.4%), lead migration (0.5%), extensor wire fracture (0.5%), extrusion (0.5%), and symptomatic ICH (0.5%). Serious adverse events occurred in 11.5% of participants, including symptomatic ICH (0.5%); device-related infections (4.1%); lead, wire, or device complications requiring reoperation (no data provided); and persistent focal weakness (0.5%). No significant differences were noted with regard to adverse event occurrence stratified by age groups, with the exception of bowstring effect, which occurred significantly higher in children (21.4%) than in adolescents (2.3%, p=0.042) and adults (1.9%, p=0.007), and was also significantly higher in participants with 4-lead DBS (9.8%) than in 2-lead DBS (1.8%) (p=0.032) and RNS (0.0%) (p=0.023). A total of 7 participants experienced bowstring effect at a median of 24 months after implantation. The authors reported that the causes for bowstring effect were wire coiling behind the generator that failed to elongate proportionally with growth (n=4) and scar formation around the neck extensor wire (n=3). Three participants underwent de-tethering, 2 were scheduled for revision during battery replacement, and 2 initially pursued conservative care but ultimately underwent explantation. A significantly higher proportion of female participants underwent device explantation compared to males (11.9% [13 of 109] vs. 1.9% [2 of 108], p=0.006). Overall, 80% of explantations were due to non-response while 20% were due to device-related infections. A total of 4 adult participants died unexpectedly after implantation. One case was a probable SUDEP at 1 year after surgery, 1 status epilepticus occurred at 2 months, and there were 2 reported suicides at 3 months and 2.6 years. Seizure frequency at death ranged from 4 to 12 per month and was comparable to or improved from baseline. The participant who died of status epilepticus had a history of SE, and both cases of suicide involved pre-existing diagnoses of major depression and previous hospitalizations, and 1 had a history of a prior suicide attempt. However, no deaths were judged to be related to device malfunction or stimulation. The observed increased risk of hardware-related complications in pediatric populations and with multi-lead DBS systems highlights the need for careful patient selection and further prospective study.

Age Consideration for RNS Treatment (Return to Position Statement)

While several retrospective case series and pooled analyses have reported on the use of responsive neurostimulation (RNS) in individuals younger than 18 years, these data are limited by small sample sizes, heterogeneous populations, lack of control groups, and reliance on subjective seizure reporting. Available evidence suggests that seizure reduction may be achieved in select pediatric populations without a clear increase in adverse events. However, these findings are derived from nonrandomized studies with significant potential for selection bias and incomplete follow-up. Importantly, there is no high-quality comparative evidence demonstrating safety and effectiveness in this population, and no randomized controlled trials have been conducted in individuals younger than 18 years. In contrast, the pivotal and long-term studies supporting RNS approval were conducted exclusively in adults, and the device remains approved by the U.S. Food and Drug Administration for use in individuals 18 years of age and older.

RNS for Non-epilepsy Indications

The use of RNS has been investigated in a small number of studies for a variety of indications including chronic pain syndromes. All of these studies were case series with low statistical power. Data from well-designed and conducted trials is needed to understand the clinical utility of cortical stimulation for conditions other than those discussed above.

Various forms of electrical stimulation have been investigated as an alternative to permanent neuroablative procedures, such as thalamotomy and pallidotomy for neuroelectrical conditions. The technique using deep brain stimulation (DBS) has been most thoroughly investigated as an alternative to thalamotomy for unilateral control of essential tremor, and tremor associated with Parkinson disease. DBS has also been investigated in individuals with primary dystonia, defined as a neurological movement disorder characterized by involuntary muscle contractions, which force certain parts of the body into abnormal, contorted and painful movements or postures and which is unrelated to any other neurological condition. According to Albanese (2013), dystonia is classified by etiology (primary or secondary dystonia), body distribution (focal, multifocal, segmental, generalized, or hemidystonia), temporal pattern (disease course or variability), or age at onset. With focal dystonia, one body region is affected. With multifocal dystonia, either two non-contiguous or more (contiguous or not) body regions are affected. Segmental dystonia occurs when two or more contiguous body regions are affected. With generalized dystonia, the trunk and at least two other sites are affected. With hemidystonia, body regions are affected on one side of the body. Disease course is further classified into static or progressive. Variability is further classified into persistent, action-specific, diurnal, or paroxysmal. Treatment options for dystonia include oral or injectable medications (for instance, botulinum toxin) and destructive surgical or neurosurgical interventions (for instance, thalamotomies or pallidotomies) when conservative therapies fail.

DBS involves the stereotactic placement of an electrode into the brain (for instance, thalamus, globus pallidus, or subthalamic nucleus). The electrode is initially attached to a temporary transcutaneous cable for short-term stimulation to validate treatment effectiveness. Several days later, the individual returns to surgery for permanent subcutaneous implantation of the cable and a radiofrequency-coupled or battery-powered programmable stimulator. The electrode is typically implanted unilaterally on the side corresponding to the most severe symptoms. However, the use of bilateral stimulation using two electrode arrays has also been investigated in individuals with bilateral, severe symptoms.

After implantation, noninvasive programming of the neurostimulator can be adjusted to the individual’s symptoms. This feature may be important for individuals with PD, whose disease may progress over time, requiring different neurostimulation parameters. Setting the optimal neurostimulation parameters may involve the balance between optimal symptom control and appearance of side effects of neurostimulation, such as dysarthria, disequilibrium, or involuntary movements.

DBS of the globus pallidus internus has demonstrated therapeutic benefit in individuals with medically refractory Meige syndrome, paralleling outcomes in other focal and segmental dystonias. Meige syndrome is a form of focal or segmental dystonia characterized by involuntary contractions of the facial, jaw, and neck muscles, most commonly presenting as a combination of blepharospasm and oromandibular dystonia. It is classified as a primary dystonia when not associated with secondary causes such as neurodegenerative disease, trauma, or medication exposure, and is among the most frequently encountered cranial dystonias in adults. The syndrome can lead to marked functional and psychosocial impairment due to difficulties with speech, eating, and eye opening. Meige syndrome is believed to result from abnormal basal ganglia-thalamocortical network activity, consistent with mechanisms described in other primary dystonias.

Responsive neurostimulation (RNS) is a newer technology proposed for the treatment of epilepsy. The RNS System is a device used for this type of treatment. The RNS System involves implantation of electrodes onto the surface or in the deeper parts of the brain near areas associated with seizure activity. Those electrodes are then attached to a control/generator unit which is also implanted in the head. The control unit monitors and records electrical activity of the brain and provides electrical stimulation when needed. Following a trial period, the initial brain activity record is evaluated by a doctor. The record is used to identify the individual’s unique pre-seizure electrical brain activity patterns and to set the RNS device to recognize and react to those patterns. Once the recognition parameters are set, the device monitors brain activity for the pre-set patterns of electrical activity. If those patterns are detected the device activates to provide stimulation through the electrodes with the goal of preventing a seizure.

Brief Scale for Anxiety (BSA): A self-report scale used to measure current anxiety symptoms, typically consisting of a short list of items rated on a point system, allowing for a quick assessment of anxiety levels in a clinical setting; it is considered a subdivision of the Comprehensive Psychopathological Rating Scale and usually includes 10 items rated on a 7-point scale.

Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) score: A numerical value used to assess the severity of dystonia, with higher scores indicating greater impairment, ranging from 0 (no dystonia) to a maximum of 120.

Clinical Global Impression (CGI) scale: A 3-item, clinician-rated scale used to assess global illness severity, overall improvement from the start of treatment, and therapeutic response.

Dystonia: A diverse group of movement disorders, all of which are characterized by involuntary muscle contractions that may cause twisting and repetitive movements or abnormal postures; dystonia is the most severe form of a group of movement disorders called dyskinesias.

Essential tremor (ET): A chronic, incurable condition with unknown cause characterized by involuntary, rhythmic tremor of a body part, most typically the hands and arms.

Global Assessment of Function (GAF) scale: A numeric scale to rate subjectively the social, occupational, and psychological functioning of an individual; scores range from 100 (extremely high functioning) to 1 (severely impaired).

Globus pallidus interna (GPi): A part of the brain involved with movement.

Humanitarian Device Exemption (HDE): Similar to a premarket approval (PMA) application, but is exempt from the effectiveness requirements of a PMA. An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose and does not pose an unreasonable or significant risk of illness or injury. The use of the device is limited to 4000 or less individuals per year.

Internal Capsule: A white matter structure in the brain that connects the cerebral cortex to the brainstem and spinal cord.

Medically refractory epilepsy: When an individual has epilepsy that persists in severity and/or frequency despite a reasonable trial of two or more antiepileptic medications.

Meige syndrome: A form of focal or segmental dystonia characterized by involuntary contractions of the facial, jaw, and neck muscles, most commonly presenting as a combination of blepharospasm and oromandibular dystonia.

Montgomery and Åsberg Depression Scale (MADRS): A 10-item questionnaire used to gauge the severity of depression in adults with mood disorders.

Multiple sclerosis: A condition of the nervous system that results in a wide variety of symptoms.

Neuropsychological testing: A series of tests that assess how well a person's brain is functioning; it can help identify neurological disorders, monitor the effects of brain injuries, and inform rehabilitation strategies (also known as a neuropsychological evaluation).

Non-epileptic seizures: A condition where a person experiences symptoms similar to an epileptic seizure, but no unusual electrical activity in the brain is present. Such non-epileptic seizures may be caused by mental stress or a physical condition. Non-epileptic seizures are also known as functional seizures, psychogenic nonepileptic seizures (PNES), psychogenic nonepileptic attacks (PNEA), psychogenic seizures, or dissociative seizures.

Nucleus accumbens: A brain structure that plays a role in many aspects of behavior, including motivation, reward, and addiction.

Parkinson disease: A progressive, incurable disease caused by the slow continuous loss of nerve cells in the part of the brain that controls muscle movement.

Post-traumatic dyskinesia: A condition where movement is altered or absent due to a traumatic injury.

Primary dystonia: A type of dystonia which is not due to a secondary cause such as stroke, cerebral palsy, tumor, trauma, infection, multiple sclerosis, medications, or a neurodegenerative disease.

Secondary dystonia: A type of dystonia which is associated with a known, acquired cause or additional neurologic abnormality where symptoms of involuntary muscle contractions are related to other conditions such as stroke, trauma, toxic substance exposure or asphyxia.

Sheehan Disability Scale: A self-report questionnaire that measures how much a person's disability impacts their work, social life, and family life.

Striatal axis: A part of the brain involved in learning, prediction and goal-directed behavior (also known as the hippocampal-striatal axis)

Stria terminalis: White matter band in the brain that connects the amygdala to the hypothalamus and other brain regions

Subthalamic nucleus (STN): A part of the brain involved with movement.

Tourette syndrome (TS): A neurological disorder characterized by multiple facial and other body tics, usually beginning in childhood or adolescence and often accompanied by grunts and compulsive utterances, such as interjections and obscenities: TS is also called Gilles de la Tourette syndrome.

Unified Parkinson’s Disease Rating Scale (UPDRS): UPDRS is a rating tool to follow the longitudinal course of Parkinson Disease and is made up of three sections: 1) mentation, behavior and mood, 2) activities of daily living and 3) motor sections evaluated by interview.

Ventralis intermediate nucleus of the thalamus (Vim): A part of the brain involved with movement.

Yale-Brown Obsessive Compulsive Scale (Y-BOCS): A measure of the severity of symptoms of OCD that is not influenced by the type or number of obsessions or compulsions present.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Deep Brain Stimulation
When services may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, for deep brain stimulation for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Responsive Neurostimulation
When services may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, for responsive neurostimulation for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

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Government Agency, Medical Society, and Other Authoritative Publications:

1. American Academy of Neurology. Evaluation of surgery for Parkinson’s disease: a report of the Therapeutics & Technology Assessment Subcommittee of the Task Force on Surgery for Parkinson’s Disease. Neurology. 1999; 53(9):1910-1921.
2. American Association of Neurological Surgeons and Congress of Neurological Surgeons (AANS/CNS). Position Statement on Intracranial Neuromodulation for Drug-Resistant Epilepsy in Pediatric Patients. August 2024. Available at: https://www.cns.org/advocacy/legislative-affairs-detail/new-powerpoint-204. Accessed on May 6, 2026.
3. Centers for Medicare and Medicaid Services. National Coverage Determination for Deep Brain Stimulation for Essential Tremor and Parkinson’s Disease. NCD #160.24. Effective April 1, 2003. Available at: https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?ncdid=279&ncdver=1&chapter=all&sortBy=title&bc=18. Accessed on May 1, 2026.
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1. American Association of Neurological Surgeons. Deep Brain Stimulation. April 15, 2024. Available at: https://www.aans.org/patients/conditions-treatments/deep-brain-stimulation/#:~:text=Deep%20brain%20stimulation%20(DBS)%20is,that%20control%20abnormal%20brain%20activity. Accessed on May 1, 2026.
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Activa Tremor Control System
BrainSense Adaptive DBS
Brio Neurostimulation System
Cerebellar Stimulation/Pacemaker
Deep Brain Stimulation for Tremor
Essential Tremor
Liberta RC DBS system
Parkinson Disease
Reclaim
RNS System
Vercise Genus^™ DBS Systems
Vercise Gevia^™
Vercise^™  PC
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