Coverage Policy Manual
Policy #: 1998099
Category: Surgery
Initiated: February 1998
Last Review: April 2022
  Electrical Stimulation, Deep Brain (e.g. Parkinsonism, Dystonia, Multiple Sclerosis, Post-Traumatic Dyskinesia)

Description:
Deep brain stimulation (DBS) involves the stereotactic implantation of an electrode into a central nervous system nucleus (e.g., hypothalamus, thalamus, globus pallidus, subthalamic nucleus). DBS is used as an alternative to permanent neuroablative procedures for control of essential tremor and Parkinson disease (PD).  DBS is also being evaluated for the treatment of a variety of other neurologic and psychiatric disorders.
 
DBS involves the stereotactic placement of an electrode into the brain (i.e., 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 patient 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 patients with bilateral, severe symptoms.
 
After implantation, noninvasive programming of the neurostimulator can be adjusted to the patient's symptoms. This feature may be important for patients with Parkinson Disease, 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.
 
Regulatory Status
In 1997, the Activa® Tremor Control System (Medtronic) was approved by the U.S. Food and Drug Administration (FDA) through the pre-market approval process for DBS. The Activa® Tremor Control System consists of an implantable neurostimulator, a deep brain stimulator lead, an extension that connects the lead to the power source, a console programmer, a software cartridge to set electrical parameters for stimulation, and a patient control magnet, which allows the patient to turn the neurostimulator on and off or change between high and low settings.
 
The original FDA-labeled indications for Activa® were limited to unilateral implantation of the device for the treatment of tremor, but, in 2002, FDA-labeled indications were expanded to include bilateral implantation as a treatment to decrease the symptoms of advanced PD Parkinson Disease not controlled by medication. In 2003, the labeled indications were further expanded to include “…unilateral or bilateral stimulation of the internal globus pallidus or subthalamic nucleus to aid in the management of chronic, intractable (drug refractory) primary dystonia, including generalized and/or segmental dystonia, hemidystonia, and cervical dystonia (torticollis) in patients seven years of age or above.” In 2018, the deep brain stimulation system received an expanded indication as an adjunctive therapy for epilepsy(P960009-S219).
 
Other Deep Brain Stimulation Systems are described below:
 
In 1997, Activa® Deep Brain Stimulation Therapy System (manufactured by Medtronic) was approved for unilateral or bilateral stimulation of the internal globus pallidus or subthalamic nucleus for symptoms of Parkinson disease or primary dystonia.
 
In 2009, the Reclaim® device (Medtronic), a DBS device, was cleared for marketing by the FDA through the humanitarian device exemption process for the treatment of severe obsessive-compulsive disorder.
  
In 2015, the Brio Neurostimulation System (St. Jude Medical) was cleared for marketing by the FDA for the treatment of Parkinsonian tremor (subthalamic nucleus) and essential tremor (thalamus).
 
In 2016, the Infinity DBS (Abbott Medical/St. Jude Medical) was approved by the FDA for treatment of Parkinsonian tremor.
 
In 2017, the Vercise Deep Brain Stimulation System (Boston Scientific), was approved by the FDA for moderate-to-advanced levodopa-responsive PD inadequately controlled with medication alone.
 
In 2018, the FDA approved the Medtronic DBS System for Epilepsy (Medtronic, Inc) through the Premarket Approval process. The intended use is bilateral stimulation of the anterior nucleus of the thalamus
 
In 2020, the Percept PC Deep Brain Stimulation (Medtronic) was approved. It records brain signals while delivering therapy for PD or primary dystonia.
 
In 2021, Vercise Genus DBS System (Boston Scientific) was approved with the indication of stimulation of the subthalamic nucleus and globus pallidus for PD.
 
In 2021, the SenSight Directional Lead System (Medtronic) was approved with the indication of unilateral or bilateral stimulation for PD, tremor, dystonia, and epilepsy.

Policy/
Coverage:
Effective April 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Unilateral or bilateral electrical deep brain stimulation of the thalamus meets primary coverage criteria for effectiveness in improving health outcomes in the treatment of disabling, medically unresponsive tremor due to essential tremor or Parkinson's disease.
 
Unilateral or bilateral deep brain stimulation of the globus pallidus or subthalamic nucleus meets member benefit  certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes in the following patients:
 
· Those with Parkinson’s disease with ALL of the following:
· A good response to levodopa; AND
· Motor complications not controlled by pharmacologic therapy; AND
· One of the following:
§ A minimum score of 30 points on the motor portion of the Unified Parkinson Disease
Rating Scale when the patient has been without medication for approximately 12 hours  OR
§ Parkinson disease for at least 4 years
 
· Patients aged greater than 7 years with chronic, intractable (drug refractory) primary dystonia, including generalized and/or segmental dystonia, hemidystonia, and cervical dystonia (torticollis).
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Deep brain stimulation for the treatment of other psychiatric or neurologic disorders, including but not
limited to multiple sclerosis, post-traumatic dyskinesia, tardive dyskinesia, Tourette syndrome,
depression, obsessive compulsive disorder, Alzheimer disease, anorexia nervosa, alcohol addiction,
chronic pain, epilepsy and chronic cluster headaches does not meet member benefit certificate
Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health
outcomes
 
For contracts without primary coverage criteria, deep brain stimulation for the treatment of other
psychiatric or neurologic disorders, including but not limited to multiple sclerosis, post-traumatic
dyskinesia, tardive dyskinesia, Tourette syndrome, depression, obsessive compulsive disorder,
Alzheimer disease, anorexia nervosa, alcohol addiction, chronic pain, epilepsy and chronic cluster
headaches, is considered investigational. Investigational services are specific contract exclusions in
most member benefit certificates of coverage.
 
Effective Prior to April 2018
Unilateral electrical deep brain stimulation of the thalamus meets primary coverage criteria for effectiveness in improving health outcomes in the treatment of disabling, medically unresponsive tremor due to essential tremor or Parkinson's disease.
 
Unilateral or bilateral deep brain stimulation of the globus pallidus or subthalamic nucleus meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes in the following patients:
    • Those with Parkinson’s disease with ALL of the following:  
        • a good response to levodopa; AND  
        • A minimal score of 30 points on the motor portion of the Unified Parkinson Disease Rating Scale (UPDRS) when the patient has been without medication for approximately 12 hours; AND
        • Motor complications not controlled by pharmacologic therapy.
    • Patients aged greater than 7 years with chronic, intractable (drug refractory) primary dystonia, including generalized and/or segmental dystonia, hemidystonia, and cervical dystonia (torticollis).
 
Deep brain stimulation for the treatment of other psychiatric or neurologic disorders, including but not limited to multiple sclerosis, post-traumatic dyskinesia, tardive dyskinesia, Tourette syndrome, depression, obsessive compulsive disorder, Alzheimer disease, anorexia nervosa, alcohol addiction, chronic pain, epilepsy and chronic cluster headaches does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes
 
For contracts without primary coverage criteria, deep brain stimulation for the treatment of other psychiatric or neurologic disorders, including but not limited to multiple sclerosis, post-traumatic dyskinesia, tardive dyskinesia, Tourette syndrome, depression, obsessive compulsive disorder, Alzheimer disease, anorexia nervosa, alcohol addiction, chronic pain, epilepsy and chronic cluster headaches, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective prior to January 2012
Unilateral electrical deep brain stimulation of the thalamus meets primary coverage criteria for effectiveness in improving health outcomes in the treatment of disabling, medically unresponsive tremor due to essential tremor or Parkinson's disease.
 
Unilateral or bilateral deep brain stimulation of the globus pallidus or subthalamic nucleus meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes in the following patients:
 
Those with Parkinson’s disease with ALL of the following:
 a good response to levodopa as  manifested by appropriate testing (e.g., UPDRS); AND
 motor complications not controlled by pharmacologic therapy. Patients aged greater than 7 years with chronic, intractable (drug refractory) primary dystonia, including generalized and/or segmental dystonia, hemidystonia, and cervical dystonia (torticollis).  
 
Patients aged greater than 7 years with chronic, intractable (drug refractory) primary dystonia, including generalized and/or segmental dystonia, hemidystonia, and cervical dystonia (torticollis).
 
Deep brain stimulation for other movement disorders, including but not limited to multiple sclerosis, tardive dyskinesia, and post-traumatic dyskinesia does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Deep brain stimulation for the treatment of other psychiatric or neurologic disorders, including but not limited to Tourette Syndrome, depression, obsessive compulsive disorder, epilepsy and chronic cluster headaches does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For contracts without primary coverage criteria, deep brain stimulation for other movement disorders, including but not limited to multiple sclerosis, tardive dyskinesia, and post-traumatic dyskinesia, is considered investigational.  
 
Deep brain stimulation for the treatment of other psychiatric or neurologic disorders, including but not limited to Tourette Syndrome, depression, obsessive compulsive disorder, epilepsy and chronic cluster headaches, is considered investigational.  Investigational services are an exclusion in the member certificate of coverage.

Rationale:
“Due to the detail of the rationale, the complete document is not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com”
 
Unilateral Deep Brain Stimulation of the Thalamus for Tremor
Tremor suppression was total or clinically significant in 82%–91% of operated sides in 179 patients who underwent implantation of thalamic stimulation devices. Results were durable for up to 8 years, and side effects of stimulation were reported as mild and largely reversible. These results are at least as good as those associated with thalamotomy. An additional benefit of deep brain stimulation is that recurrence of tremor may be managed by changes in stimulation parameters.
 
Unilateral or Bilateral Stimulation of the Globus Pallidus or Subthalamic Nucleus
A wide variety of studies consistently demonstrate that deep brain stimulation of the globus pallidus or subthalamic nucleus results in significant improvements as measured by standardized rating scales of neurologic function. The most frequently observed improvements consist of increased waking hours spent in a state of mobility without dyskinesia, improved motor function during “off” periods when levodopa is not effective, reduction in frequency and severity of levodopa-induced dyskinesia during periods when levodopa is working (“on” periods), improvement in cardinal symptoms of Parkinson’s disease during periods when medication is not working, and in the case of bilateral deep brain stimulation of the subthalamic nucleus, reduction in the required daily dosage of levodopa and/or its equivalents. The magnitude of these changes is both statistically significant and clinically meaningful. The beneficial treatment effect lasts at least for the 6–12 months observed in most trials. While there is not a great deal of long-term follow-up, the available data are generally positive.
 
Adverse effects and morbidity are similar to those known to occur with thalamic stimulation. Deep brain stimulation possesses advantages to other treatment options. In comparison to pallidotomy, deep brain stimulation can be performed bilaterally. The procedure is non-ablative and reversible.
 
Deep brain stimulation for the treatment of primary dystonia received FDA approval through the Humanitarian Device Exemption (HDE) process. The HDE approval process is available for those conditions that effect less than 4,000 Americans per year. According to this approval process, the manufacturer is not required to provide definitive evidence of efficacy, but only probable benefit. The approval was based on the results of DBS in 201 patients represented in 34 manuscripts.  There were 3 studies that reported at least 10 cases of primary dystonia. In these studies, clinical improvement ranged from 50% to 88%. A total of 21 pediatric patients were studied; 81% were older than 7 years. Among these patients there was about a 60% improvement in clinical scores. As noted in the analysis of risk and probably benefit, the only other treatment options for chronic refractory primary dystonia are neurodestructive procedures. Deep brain stimulation provides a reversible alternative. The FDA Summary of Safety and Probable Benefit states, “Although there are a number of serious adverse events experienced by patients treated with deep brain stimulation, in the absence of therapy, chronic intractable dystonia can be very disabling and in some cases, progress to a life-threatening stage or constitute a major fixed handicap. When the age of dystonia occurs prior to the individual reaching their full adult size, the disease not only can affect normal psychosocial development but also cause irreparable damage to the skeletal system. As the body of the individual is contorted by the disease, the skeleton may be placed under constant severe stresses that may cause permanent disfigurement. Risks associated with deep brain stimulation for dystonia appear to be similar to the risk associated with the performance of stereotactic surgery and the implantation of deep brain stimulation systems for currently approved indications, except when used in either child or adolescent patient groups.”
 
Since the FDA approval, there have been additional published trials of deep brain stimulation for dystonia, which continue to report positive results.  Vidailhet and colleagues reported the results of a prospective multi-institutional case series of 22 patients with primary generalized dystonia. Symptoms were evaluated prior to surgery and at several points up to 1 year of follow-up, in a double-blind fashion with the stimulator turned on and off. Dystonia scores were significantly better with the neurostimulator turned on.
 
Deep Brain Stimulation for the Treatment of Headaches
Deep brain stimulation of the posterior hypothalamus for the treatment of chronic cluster headaches has been investigated since recent functional studies have suggested cluster headaches have a central hypothalamic pathogenesis. Franzini and colleagues and Leone et al, reported deep brain stimulation with long-term, high-frequency, electrical stimulation of the ipsilateral posterior hypothalamus resulted in long-term pain relief (1–26 months of follow-up) without significant adverse effects in 5–8 patients with chronic cluster headaches.  The results from these reports seem promising; however, the authors note further studies are needed to determine the long-term safety and effectiveness of this treatment.
 
A search of the MEDLINE database for the period of January 2006 to August 2007 identified a number of papers on the topic of deep brain stimulation. A systematic review of 34 studies (921 patients) examined outcomes following subthalamic stimulation for patients with Parkinson’s disease who had failed medical management (e.g., motor fluctuations, dyskinesia, and other medication side effects).  Twenty studies, primarily class IV (uncontrolled cohorts or case series), were included in the meta-analysis. Subthalamic stimulation was found to improve activities of daily living by 50% over baseline as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) part II (decrease of 13.35 points out of 52). There was a 28-point decrease in the UPDRS III score (out of 108) indicating a 52% improvement in the severity of motor symptoms while the patient was not taking medication. A strong relationship was found between the pre-operative dose response to L-dopa and improvements in both the UPDRS II and III. The analysis found a 56% reduction in medication use, a 69% reduction in dyskinesia, and a 35% improvement in quality of life with subthalamic stimulation.
 
Two randomized trials assessed the efficacy of subthalamic stimulation for Parkinson’s disease. The German Parkinson Study Group randomized 78 patient pairs with advanced Parkinson’s disease and severe motor symptoms to either subthalamic stimulation or medical management.  Subthalamic stimulation improved severity of symptoms without medication in 55 of 78 pairs (from 48 to 28 on the UPDRS III). Improvements in quality of life were greater than medical management in 50 of 78 pairs (average change from 42 to 32 on the 100 point Parkinson’s Disease Questionnaire), with 24% to 38% improvements in subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation (13% vs. 4%) and included a fatal intracerebral hemorrhage. Another European multicenter study assessed whether subthalamic stimulation might maintain quality of life and motor function if performed earlier in the course of the disease.  Ten matched patient pairs younger than 55 years of age with mild to moderate motor signs were randomly assigned to deep brain stimulation or medical management. There was no difference in the severity of Parkinsonian motor disability while “on” medication. However, in the medically treated patients both the daily dose of levodopa and the severity of levadopa-induced motor complications increased over the 18 months of the study (12% and 15%, respectively), while in the surgical patients the daily dose of levodopa was reduced by 57% and the severity of levodopa-induced motor complications improved by 83%. Additional studies are needed to determine the long-term effect of subthalamic stimulation in this younger patient population.
 
The Deep-Brain Stimulation for Dystonia Study Group compared bilateral pallidal neurostimulation with sham stimulation in 40 patients with dystonia who had failed medical management (3-month randomized trial with a 6-month open-label extension).  Blinded assessment with the Burke-Fahn-Marsden Dystonia Rating Scale found improvements in the movement score (16 points versus 1.6 points in sham controls), which corresponded to a 39% reduction in symptoms. Disability scores improved by 4 points in the neurostimulation group compared with a 0.8 point improvement in the control subjects (38% improvement). The study found a 30% improvement in quality of life (change of 10 versus 4 points in controls) following stimulation of the globus pallidus. There was high variability in baseline scores and in the magnitude of improvement; 6 patients (17%) were considered to have failed treatment (< 25% improvement), 5 patients (25%) improved by more than 75%. No single factor was found to predict the response to treatment. Independent assessors found similar improvements in the control group after the 6-month open-label extension.
 
Stimulation of the globus pallidus has also been examined as a treatment of tardive dyskinesia in a phase II double-blinded (presence and absence of stimulation) multicenter study.  The trial was stopped early due to successful treatment (greater than 40% improvement) in the first 10 patients. Additional studies with more patients and longer follow-up are needed. Prospective, controlled trials are lacking for other disorders. Stimulation of the posterior hypothalamus was reported to have completely resolved headache in 10 of 16 chronic cluster headache patients and in one patient with neuralgiform headache; treatment failed in 3 of 3 patients who had atypical facial pain.  In addition to the areas of research discussed above, deep brain stimulation is being investigated for the treatment of Tourette syndrome, depression, obsessive compulsive disorder, and epilepsy.  Evidence remains insufficient to evaluate the efficacy of deep brain stimulation for these disorders.
 
2009 Update
Neurological Applications
The policy was updated with a MEDLINE® search.  Schuurman and colleagues followed 65 patients comparing thalamic stimulation and thalamotomy for treatment of tremor due to Parkinson’s disease (PD) , essential tremor (ET), and multiple sclerosis (MS). After 5 years, 48 patients were available for follow-up.  The primary outcome measure was functional status on the Frenchay Activities Index (FAI); secondary measures were tremor severity, frequency of complications, and patients’ assessment of outcome. The mean difference in FAI scores was 4.4 (95% CI: 1.1–7.7) after 6 months, 3.3 (95% CI: 0.03–6.6) after 2 years and 4.0 (95% CI: 0.3–7.7) after 5 years in favor of stimulation. Tremor suppression was equally effective after both procedures, and stable in PD patients. A diminished effect was observed in half of the patients with ET and MS. Small numbers of patients with ET and MS limit conclusions with respect to these conditions. Neurological adverse effects were higher after thalamotomy. Subjective assessments favored stimulation (Schuurman, 2008).  Hariz et al. evaluated outcomes of thalamic deep brain stimulation in patients with tremor predominant PD who participated in a multicenter European study and reported that, at 6 years post-surgery, tremor was still effectively controlled and appendicular rigidity and akinesia remained stable when compared with baseline (Hariz, 2008).
 
Weaver and colleagues report 6-month outcomes of a multicenter randomized, controlled trial comparing DBS with best medical therapy for patients with advanced PD. Of 278 patients that were screened, 255 were randomized; 134 to best medical therapy and 121 to DBS (61 to stimulation of the globus pallidus and 60 to stimulation of the subthalamic nucleus). By intention-to-treat analysis, patients who received DBS gained a mean of 4.6 hours/day of on time without troubling dyskinesia compared to no hours gained for patients receiving best medical therapy (p<0.001). Seventy-one percent of DBS patients experienced clinically meaningful motor function improvements (i.e., >5 point change in Unified Parkinson Disease Rating Scale of motor function) versus 32% of best medical therapy group. Significantly greater improvements in quality of life measures were achieved by DBS patients. At least one serious adverse event occurred in 49 DBS patients versus 15 in the best medical therapy patients, including 39 related to the surgical procedure and one death secondary to cerebral hemorrhage (Weaver, 2009).
 
Witt et al. performed an ancillary protocol as part of a multicenter randomized, controlled trial (previously reviewed, Deuschl et al., 2006 ) to assess neuropsychiatric consequences of DBS in patients with Parkinson’s disease (Witt, 2008).  One hundred-twenty-three patients with PD and motor fluctuations were randomized to DBS or best medical treatment. Neuropsychological and psychiatric examinations at baseline and 6 months post-implantation were compared. DBS of the subthalamic nucleus did not reduce overall cognition or affectivity. There was a selective decrease in frontal cognitive functions and an improvement in anxiety in patients after treatment that did not affect improvements in quality of life.
 
Appleby et al. report on a meta-analysis focused on adverse events associated with DBS in order to assess the risks and benefits of the treatment as they relate to its potential use in the psychiatric setting (Appleby, 2007).  They concluded that DBS is an effective treatment for PD, dystonia, and essential tremor and rates of depression, cognitive impairment, mania, and behavior change are low. Prevalence of depression was 2–4%, mania 0.9–1.7%, emotional changes 0.1–0.2%, and suicidal ideation/suicide attempt was 0.3–0.7%. The completed suicide rate was 0.16–0.32%. In light of the rate of suicide in patients treated with DBS, particularly with thalamic and globus pallidus interna (GPi) stimulation, the authors argue for prescreening patients for suicide risk.
 
A number of recent papers, mainly case series, focus on the use of DBS for treatment of dystonia. Vidailhet et al. compared outcomes at 3 years with those reported at 1 year for the 22 patients in their study of bilateral, pallidal DBS for generalized dystonia referenced in a previous update (Vidailhet, 2005) and found that the motor improvement observed at 1 year was maintained. At 3 years, measures of cognition and mood were unchanged from baseline and 1 year evaluations (Vidailhet, 2007).  Egidi et al. retrospectively reviewed records of 69 patients treated in multiple Italian centers with DBS implanted in the GPi; 37 patients had primary and 32 had secondary dystonia. Improvement of at least 50% in Burke-Fahn-Marsden severity scale was reached by 45% of primary and 37% of secondary dystonia patients at 3–84 months’ follow-up (longer than 24 months in half of the patients) (Egidi, 2007).  
 
Other Neurological Applications
No controlled trials of DBS for seizures were identified. A multicenter, randomized controlled trial of stimulation of the anterior nucleus of the thalamus in epilepsy (SANTE) is in progress. Two small cross-over studies of DBS for Tourette syndrome were identified, one comparing unilateral and bilateral stimulation (5 patients) and the other with 3 patients comparing thalamic, pallidal, simultaneous thalamic and pallidal, and sham stimulation (Maciunas, 2007) (Welter, 2008).  No controlled trials of DBS for tardive dyskinesia or cluster headache were found.
 
Psychiatric Applications
A crossover, double-blind, multicenter study of DBS for treatment of refractory obsessive-compulsive disorder (OCD) is reported by Mallet et al (Mallet, 2008).  Eighteen patients were enrolled, one withdrew and one required removal of the stimulator before randomization because of infection. Three months after surgery, 8 patients 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. It was recommended that medical treatment remain stable and adjustments necessitated by the patient’s psychiatric condition were recorded. Medication was held constant during the 10-month protocol, except for transient increase in benzodiazepine therapy in 3 patients and augmentation of neuroleptic treatment in one patient for exacerbated anxiety. The primary outcome measure was severity of OCD as assessed by the Yale-Brown Obsessive Compulsive Scale (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. Patients 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 Asberg Depression Scale (MADRS), Brief Scale for Anxiety, 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 patients, the most serious 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 patients 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, in order to preserve blinding, stimulation settings were kept below the threshold known to induce adverse effects and may have been too low to reduce symptoms. They conclude that their finding suggest that DBS may lessen severity of symptoms; however, serious adverse events did occur. Larger studies with longer follow-up are needed including evaluation of quality of life and ability to function in social and work situations (Mallet, 2008).
 
Sachdev and Chen note in a January 2009 review that there has been a shift of interest in psychosurgery away from ablative techniques and toward deep brain stimulation (Sachdev, 2009).  Studies of DBS for depression and obsessive compulsive disorder, however, are few and involve small numbers of subjects and “more data are needed on technical details and outcomes before the possible therapeutic role of DBS can be established.”
 
In summary, these multiple recent publications support current policy; they also reflect interest in DBS as a potential treatment for a growing number of additional clinical indications. The current policy statements are unchanged.
 
2012 Update
Stimulation of the Globus Pallidus and Subthalamic Nucleus for Advanced Parkinson’s Disease
In 2010, Williams et al. reported results from an ongoing randomized, multicenter open-label trial (PD SURG) from 13 neurosurgical centers in the United Kingdom (Williams, 2010). Included in the study were 366 patients with PD that was not adequately controlled by medical therapy. Patients were randomized to surgery (all had DBS) and best medical therapy, or to best medical therapy alone. The study was designed to detect a 10-point difference (regarded as clinically important) in the Parkinson’s disease questionnaire (PDQ) summary index. Five of 183 patients randomized to surgery did not have surgery, and 12 of 183 patients randomized to medical therapy had surgery within the first year of the study (patients were analyzed in the treatment group to which they were randomized). In 174 patients, the subthalamic nucleus was the surgical target, and 176 of 178 procedures were bilateral. At 1 year, the mean improvement in the primary outcome measure, the PDQ summary index, was 5.0 points in the DBS group and 0.3 points in the control group. The difference in mean change in PDQ between the 2 groups was -8.9 for the mobility domain, -12.4 for the daily living domain, and -7.5 for the bodily discomfort domain. Differences between groups in the other domains were not significant. Thirty-six (19%) patients had serious surgery-related adverse events; there was one procedure-related death. The most common surgery-related serious adverse events were infections (n=16).
 
Epilepsy
In 2010, Fisher et al. reported a U.S. multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for epilepsy (SANTE) (Fisher, 2010). Included were 110 patients 18-65 years old, with partial seizures including secondarily generalized seizures, at least 6 per month, but no more than 10 per day. An additional 47 patients were enrolled in the study but did not undergo implantation. At least 3 antiepileptic drugs must have failed to produce adequate seizure control prior to baseline, with 1 to 4 antiepileptic drugs used at the time of study entry. Half of the patients were randomized to stimulation during a 3-month blinded phase; then all patients received unblinded stimulation. The baseline monthly median seizure frequency was 19.5. During the first and second months of the blinded phase, the difference in seizure reduction between stimulation on and stimulation off (-42.1% vs. -28.7%, respectively) was not significantly different. In the last month of the blinded phase, the stimulated group had a greater reduction in seizures compared with the control group (-40.4% vs. -14.5% in controls). The median change in seizure frequency was -41% at 13 months and -56% at 25 months. The stimulation group experienced fewer seizure-related injuries than patients in the control group (7.4% vs. 25.5%, respectively). Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression (8 vs. 1) or memory problems (7 vs. 1 – both respectively) as adverse events. There was a progressive reduction in seizure frequency over long-term follow-up. By 2 years, 54% of patients had a seizure reduction of equal to or greater than 50%, and 14 patients (13%) were seizure-free for at least 6 months. The most common device-related adverse events were paresthesias in 18.2% of participants, implant site pain in 10.9%, and implant site infection in 9.1%. Eighteen participants (16.4%) withdrew from the study after the implantation because of adverse events. There were 5 deaths, none of which were considered to be device-related. Although some patients appear to have benefited from treatment during the extended follow-up phase, the difference between groups in the blinded portion of the study was modest. Additional study is needed to establish the safety and efficacy of this treatment.
 
Tourette Syndrome
A 2012 systematic review identified 25 published studies, representing data from 69 patients, that reported on the efficacy of DBS in the treatment of Tourette syndrome (Sleeves, 2012).  However, only 3 studies with methodologic quality ratings of fair to poor met the inclusion criteria for evidence-based analysis. These 3 studies are described below. The authors recommend that DBS continues to be considered an experimental treatment for severe, medically refractory tics.
 
Another systematic review from 2012 examined patient and target selection for DBS of Tourette syndrome (Pansaon, 2012). The majority of clinical trials for DBS in Tourette syndrome have targeted the medial thalamus at the crosspoint of the centromedian nucleus, substantia periventricularis, and nucleus ventro-oralis internus. Other targets that have been investigated include the subthalamic nucleus, caudate nucleus, globus pallidus internus, and the anterior limb of the internal capsule and nucleus accumbens. The review found no clear consensus in the literature for which patients should be treated and what the best target is. Additional study is needed to clarify these issues.
 
In 2011, Ackermans et al. reported preliminary results of a double-blind crossover trial of thalamic stimulation (centromedian nucleus – substantia periventricularis- nucleus ventro-oralis internus crosspoint) in 6 patients with refractory Tourette syndrome (Ackermans, 2011). Tic severity during 3 months of stimulation was significantly lower than during the 3 months with the stimulator turned off, with a 37% improvement on the Yale Global Tic Severity Scale (mean 25.6 vs. 41.1) and a decrease in tic severity of 49% at 1 year after surgery compared to preoperative assessments (mean 21.5 vs. 42.2 – both respectively). Secondary outcomes (change in associated behavioral disorder and mood) were not altered by the stimulation. Serious adverse events included one small hemorrhage ventral to the tip of the electrode, one infection of the pulse generator, subjective gaze disturbances, and reduction of energy levels in all patients. The interim analysis led to the termination of the trial. The authors commented that further RCTs on other targets are urgently needed since the search for the optimal one is still ongoing.
 
Hypothalamic Stimulation for the Treatment of Cluster Headaches and Facial Pain
Deep brain stimulation of the posterior hypothalamus for the treatment of chronic cluster headaches has been investigated, since functional studies have suggested cluster headaches have a central hypothalamic pathogenesis. In 2010, Fontaine et al. published results from a prospective crossover, double-blind, multicenter study in 11 patients with DBS of the posterior hypothalamus for severe refractory chronic cluster headache (Fontaine, 2010). The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. Severity of cluster headache was assessed by the weekly attacks frequency (primary outcome), pain intensity, sumatriptan injections, emotional impact, and quality of life (short-form 12 [SF-12]). During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6 of 11 patients reported a greater than 50% reduction in the weekly frequency of attacks.
 
Obsessive-Compulsive Disorder
A systematic review of DBS for obsessive-compulsive disorder (OCD) was published in 2011 (de Koning, 2011). The review included 9 case studies and 7 controlled studies with a blinded on-off phase. It was estimated from the published trials and case studies that more than 100 individuals have received experimental DBS for OCD in 5 different targets. These targets are the anterior limb of the internal capsule (ALIC), subthalamic nucleus, ventral capsule/ventral striatum, nucleus accumbens, and inferior thalamic peduncle. The most common measure of efficacy is a reduction in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The Y-BOCS is a 10-item scale in which higher scores reflect more intense symptoms, and a score of 24 or more (of a possible 40) is considered severe illness. Most studies designate a therapeutic response as a Y-BOCS reduction of 35% or more from the pretreatment baseline with a reduction of 25% or more considered a partial response.
 
Nucleus Accumbens
Denys et al. reported a double-blind crossover study of bilateral DBS of the nucleus accumbens in 16 patients with refractory OCD in 2010 (Denys, 2010). Patients with a score of equal to or greater than 28 on the Y-BOCS, and an equal to or greater than 5-year history of OCD that was refractory to medical treatment were included. Out of 101 patients screened for the study, 16 underwent implantation. The study consisted of 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. Once a decrease in Y-BOCS was obtained, a standardized cognitive behavioral therapy (CBT) program was added. In the open phase, the mean Y-BOCS score decreased by 46% from 33.7 at baseline to 18.0 after 8 months. Nine of 16 patients were responders (Y-BOCS decrease > 35%), with a mean decrease of 23.7 points. In the double-blind, sham-controlled phase (n=14), there was a mean 8.3 point difference in the Y-BOCS score between active and sham stimulation. Depression and anxiety decreased significantly, with a mean difference in Hamilton anxiety (HAM-A) scores of 12.1 and in Hamilton depression (HAM-D) scores of 11.3. Except for mild forgetfulness and word-finding problems, no permanent adverse events were reported. The most prominent adverse event related to stimulation was elevated mood or hypomania.
 
A double-blind crossover study of unilateral DBS of the nucleus accumbens was reported by Huff et al. in 2010 (Huff, 2010). Patients with a score of equal to or greater than 25 on the Y-BOCS, and an equal to or greater than 5-year history of OCD that was refractory to medical treatment were included. Ten patients received 3 months of DBS followed by 3 months of sham stimulation, or vice versa. After 6 months, stimulation was continued unblinded with the option to change stimulation parameters every 3 months (including activation of electrodes in the ALIC). The patients had an examination at baseline, within the first week, and at 3, 6, 9, and 12 months by a psychiatrist who was blinded to the treatment condition. The mean Y-BOCS at baseline was 32.2. There was no difference in Y-BOCS during the crossover period with a score of 27.9 during the on period and 31.1 during the off period. After 12 months the Y-BOCS had significantly decreased to 25.4. Logistic regression revealed no independent effect for changes in stimulation amplitude, changes in active contacts, or changes in medication. Five of 10 patients showed a decrease of equal to or greater than 25%, indicating a partial response. Only 1 patient showed a decrease in Y-BOCS of greater than 35%. Depression, global functioning, and quality of life improved within 1 year, while anxiety, global symptom severity, and cognitive function showed no significant changes.
 
Ventral Capsule/Ventral Striatum
Goodman et al. reported a double-blinded pilot crossover study of DBS of the ventral capsule/ventral striatum in 6 patients (Goodman, 2010). Patients with a score of equal to or greater than 28 on the Y-BOCS and a > 5-year history of OCD that was refractory to medical treatment were included. All 6 patients had a lifetime diagnoses of major depression that was deemed secondary to OCD, 1 met criteria for a current diagnosis of major depression. The mean duration of illness was 24 years (range, 11-35 years). The first patient was implanted in 2003; the sixth patient completed 12 months of DBS in 2008. The baseline Y-BOCS was 33.7. For the crossover phase, there was a reduction of 5.33 points with the stimulator turned on (n=3) and -0.67 with the stimulator off (n=3, not significantly different). After 12 months of stimulation, 4 (66.7%) of patients were responders (> 35% improvement and a score < 16 on the Y-BOCS). Depressive symptoms improved significantly in the group as a whole; global functioning improved in the 4 responders. The authors concluded that future research should attend to subject selection, lead location, DBS programming, and mechanisms underlying the therapeutic benefits.
 
Treatment-Resistant Depression
A variety of target areas are being investigated in case series for DBS of treatment-resistant depression, including the subcallosal cingulate gyrus, the ventral capsule/ventral striatum, and the nucleus accumbens. No randomized controlled trials have been identified.
 
In 2012, Holtzheimer et al. reported a Phase I/II open-label trial of DBS with a single-blind sham lead-in phase for treatment-resistant unipolar and bipolar depression (Holtzheimer, 2012). Ten patients with treatment-resistant major depressive disorder and 7 patients with treatment-resistant bipolar II disorder were included in the study. Inclusion criteria included a current major depressive episode of at least 12 months’ duration, a score of 20 or higher on the Hamilton Depression Rating Scale (HAM-D) not responding to at least 4 adequate antidepressant treatments, and a lifetime failure or inability to receive electroconvulsive therapy. The target of DBS was subcallosal cingulate white matter. The mean HAM-D score was 20.5 at the end of the sham lead-in phase, decreasing to 13.1 at 24 weeks (n=16), 13.6 at 1 year (n=14), and 7.3 at 2 years (n=11). Remission rates, defined as a HAM-D score of less than 8, were 18% at 24 weeks, 36% at 1 year, and 58% after 2 years. Response rates, defined as 50% or greater change in the HAM-D, were 41% after 24 weeks, 36% after 1 year and 92% after 2 years. The first 3 patients underwent a single-blind discontinuation phase after 24 weeks, and all 3 had full relapse with increased suicidal ideation. Because of patient safety concerns, this phase was eliminated for subsequent patients. No patient achieving remission experienced a relapse during stimulation. Efficacy was similar for patients with major depression and those with bipolar depression.
  
Guidelines
The European Society for the Study of Tourette Syndrome (ESSTS) published guidelines on DBS in 2011 (Muller-Vahl, 2011). The guidelines state that DBS for Tourette syndrome is still in its infancy and that there are no randomized controlled studies available that include a sufficiently large number of patients. There was general agreement among the workgroup members that DBS should only be used in adult, treatment-resistant, and severely affected patients, and it was highly recommended that DBS be performed in the context of controlled and double-blind trials including larger and carefully characterized groups of patients.
 
Summary
In summary, evidence for efficacy of deep brain stimulation for Tourette syndrome, obsessive-compulsive disorder, tardive dystonia, and cluster headache is based on experience with very small numbers of patients. In addition, the appropriate candidates and most effective target areas for DBS are under investigation. Additional controlled studies are required to evaluate the role of DBS for these conditions.  Except for minor changes in the criteria for coverage of deep brain stimulation for the treatment of the globus pallidus or subthalamic nucleus, the coverage statement is unchanged.
 
2013 Update
A literature search was conducted through January 2013.  There was no new literature identified that would prompt a change in the coverage statement. The following is a summary of the key identified literature.
 
Tourette Syndrome
A 2012 systematic review identified 25 published studies, representing data from 69 patients, that reported on the efficacy of DBS in the treatment of Tourette syndrome (Steeves, 2012). However, only 3 studies with methodological quality ratings of fair to poor met the inclusion criteria for evidence-based analysis. These 3 studies are described below. The authors recommend that DBS continues to be considered an experimental treatment for severe, medically refractory tics.
 
Another systematic review from 2012 examined patient and target selection for DBS of Tourette syndrome (Pansaon, 2012). The majority of clinical trials for DBS in Tourette syndrome have targeted the medial thalamus at the crosspoint of the centromedian nucleus, substantia periventricularis, and nucleus ventro-oralis internus. Other targets that have been investigated include the subthalamic nucleus, caudate nucleus, globus pallidus internus, and the anterior limb of the internal capsule and nucleus accumbens. The review found no clear consensus in the literature for which patients should be treated and what the best target is. Additional study is needed to clarify these issues.
 
Treatment-Resistant Depression
A variety of target areas are being investigated in case series for DBS of treatment-resistant depression, including the subcallosal cingulate gyrus, the ventral capsule/ventral striatum, and the nucleus accumbens. No randomized controlled trials have been identified.
 
In 2012, Holzheimer et al. reported a phase I/II open-label trial of DBS with a single-blind sham lead-in phase for treatment-resistant unipolar and bipolar depression (Holtzheimer, 2012). Ten patients with treatment-resistant major depressive disorder and 7 patients with treatment-resistant bipolar II disorder were included in the study. Inclusion criteria included a current major depressive episode of at least 12 months’ duration, a score of 20 or higher on the Hamilton Depression Rating Scale (Ham-D) not responding to at least 4 adequate antidepressant treatments, and a lifetime failure or inability to receive electroconvulsive therapy. The target of DBS was subcallosal cingulate white matter. The mean Ham-D score was 20.5 at the end of the sham lead-in phase, decreasing to 13.1 at 24 weeks (n=16), 13.6 at 1 year (n=14), and 7.3 at 2 years (n=11). Remission rates, defined as a Ham-D score of less than 8, were 18% at 24 weeks, 36% at 1 year, and 58% after 2 years. Response rates, defined as 50% or greater change in the Ham-D, were 41% after 24 weeks, 36% after 1 year and 92% after 2 years. The first 3 patients underwent a single-blind discontinuation phase after 24 weeks and all 3 had full relapse with increased suicidal ideation. Because of patient safety concerns, this phase was eliminated for subsequent patients. No patient achieving remission experienced a relapse during stimulation. Efficacy was similar for patients with major depression and those with bipolar depression.
 
Practice Guidelines and Position Statements
The American Academy of Neurology published an updated guideline on the treatment of essential tremor in 2011 (Zeisiewicz, 2011). There were no changes from the conclusions and recommendations of the 2005 practice parameters regarding DBS for essential tremor (Zesiewicz, 2005). The guidelines stated that DBS of the thalamic nucleus may be used to treat medically refractory limb tremor (level C, possibly effective), but that there is insufficient evidence to make recommendations regarding the use of thalamic DBS for head or voice tremor (level U, treatment is unproven).
 
2014 Update
A literature search conducted through June 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
A systematic review from 2014 identified 22 published reports with 6 different approaches/targets including the nucleus accumbens, ventral striatum/ventral capsule, subgenual cingulate cortex, lateral habenula, inferior thalamic nucleus, and medial forebrain bundle (Morishita, 2014). Only 3 of the studies identified were controlled with sham stimulation periods, and as of December 2013, there were 2 unpublished multicenter, randomized, controlled trials evaluating subgenual cingulate cortex and ventral striatum/ventral capsule DBS that had been terminated due to futility (interim analysis demonstrating very low probability of success if trial was completed as planned).
 
2006 Guidelines from AAN on the treatment of PD with motor fluctuations and dyskinesia found that although the criteria are evolving, patients with PD who are considered candidates for DBS include levodopa-responsive, non-demented, and neuropsychiatrically intact patients who have intractable motor fluctuations, dyskinesia, or tremor (Pahwa, 2006). AAN concluded that DBS of the subthalamic nucleus may be considered as a treatment option in PD patients to improve motor function and to reduce motor fluctuations, dyskinesia, and medication usage (Level C – possibly effective), but found insufficient evidence to make any recommendations about the effectiveness of DBS of the globus pallidus or the ventral intermediate nucleus of the thalamus in reducing motor complications or medication usage, or in improving motor function in PD patients.
 
2010 Guidelines from AAN on the treatment of non-motor symptoms of Parkinson disease found insufficient evidence for the treatment of urinary incontinence with DBS of the subthalamic nucleus (Zesiewicz, 2010). AAN found that DBS of the subthalamic nucleus possibly improves sleep quality in patients with advanced Parkinson disease. However, none of the studies performed DBS to treat insomnia as a primary symptom, and DBS of the subthalamic nucleus is not currently used to treat sleep disorders.
 
2013 Guidelines from AAN on the treatment of tardive syndromes states that the available evidence, which consists of Class IV studies comprising case reports or small case series, is insufficient to support or refute pallidal DBS for tardive syndromes (Bhidayasiri, 2013).
 
In 2006, NICE published a clinical guideline on the diagnosis and management of Parkinson disease in primary and secondary care (NICE, 2006). With the evidence at that time it was not possible to decide if the subthalamic nucleus or globus pallidus interna is the preferred target for deep brain stimulation for people with PD, or whether one form of surgery is more effective or safer than the other. Based on level 3 or 4 evidence, NICE concluded that thalamic deep brain stimulation may be considered as an option in people with PD who predominantly have severe disabling tremor and where subthalamic nucleus stimulation cannot be performed.
 
2017 Update
A literature search conducted through March 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Parkinson Disease with Early Motor Complications
Schuepbach and colleagues published an RCT evaluating DBS in patients with PD and early motor complications (Schuepbach, 2013). Key eligibility criteria included age 18 to 60 years, disease duration of at least 4 year, improvement of motor signs of at least 50% with dopaminergic medication, and PD disease severity below stage 3 in the on-medication condition. At total of 251 patients enrolled, 124 of who were assigned to DBS plus medical therapy and 127 to medical therapy alone. Analysis was intention to treat and blinded outcome assessment was done at baseline and 2 years.
 
The primary end point was mean change from baseline to 2 years in the summary index of the Parkinson Disease Questionnaire (PDQ-39), which has a maximum score is 39 points, with higher scores indicating higher QOL. Mean baseline scores on the PDQ-39 were 30.2 (SD=1.3) in the DBS plus medical therapy group and 30.2 (SD=1.2) in the medical therapy only group. At 2 years, the mean score increased by 7.8 points (SD=1.2) in the DBS plus medical therapy group and decreased by 0.2 points (SD=1.1) in the medical therapy only group. There was a significant difference between groups in the mean change, 8.0 (SD=1.6) (p=0.002). There were also significant between-group differences in major secondary outcomes, favoring the DBS plus medical therapy group (p<0.01 on each). These outcomes included severity of motor signs, ADLs, severity of treatment-related complications, and the number of hours with good mobility and no troublesome dyskinesia. The first 3 secondary outcomes were assessed using UPDRS subscales. Regarding medication use, the levodopa-equivalent daily dose was reduced by 39% in the DBS plus medical therapy group and increased by 21% in the medical therapy only group.
 
Sixty-eight patients in the DBS plus medical therapy group and 56 in the medical therapy only group experienced at least 1 serious adverse event (SAE). This included 26 SAEs in the DBS group that were surgery- or device-related; reoperation was necessary in 4 patients.
 
GPi vs STN Stimulation
A review by Tan and colleagues included RCTs evaluating patients with PD who were responsive to levodopa, had at least 6 months of follow-up, and reported at least 1 of the following outcome measures: UPDRS-III, Beck Depression Inventory-II (BDI), levodopa-adjusted dose (LED), neurocognitive status, or QOL (Tan, 2016). Ten RCTs met eligibility criteria and were included in the quantitative synthesis. After 6 months, there were no significant differences in the UPDRS-III scores between the GPi and STN groups for patients in the off-medication/on-simulation state (5 studies; MD = -1.39; 95% CI, -3.70 to 0.92) or the on-medication/on-stimulation state (5 studies; MD = -0.37; 95% CI, -2.48 to 1.73). At the 12- and 24-month follow-up, only 1 to 3 studies reported data on the UPDRS-III score. A pooled analysis of LED, there was a significant difference between the GPi and STN groups, favoring STN (6 studies; MD=0.60; 95% CI, 0.46 to 0.74). However, the analysis of BDI-II scores favored the GPI group (4 studies; MD = -0.31; 95% CI, -0.51 to -0.12). Other meta-analyses had similar mixed findings and none concluded that 1 type of stimulation was clearly better than the other for patients with advanced PD.
 
Treatment-Resistant Depression
A crossover RCT evaluating active and sham phases of DBS stimulation in 25 patients with treatment-resistant depression was published by Bergfeld and colleaues (Bergfeld, 2016). Prior to the randomized phase, all patients received 52 weeks of open-label DBS treatment with optimization of settings. Optimization ended when patients achieved a stable response of at least 4 weeks or after the 52-week period ended. At the end of the open-label phase, 10 (40%) patients were classified as responders (≥50% decrease in the Hamilton Depression Rating Scale [HAM-D] score) and 15 (60%) patients were classified as nonresponders. After the 52 weeks of open-label treatment, patients underwent 6 weeks of double-blind active and sham stimulation. Sixteen (64%) of 25 enrolled patients participated in the randomized phase (9 responders, 7 nonresponders). Nine patients were prematurely crossed over to the other intervention. Among all 16 randomized patients, HAM-D scores were significantly higher at the end of the active stimulation phase (mean HAM-D score, 16.5) than the sham stimulation phase (mean HAM-D score, 23.1; p<0.001). Mean HAM-D scores were similar after the active (19.0) and sham phases in initial nonresponders (23.0). Among initial responders, mean HAM-D score was 9.4 after active stimulation and 23 after sham stimulation. Trial limitations included the small number of patients in the randomized phase and potential bias from having an initial year of open-label treatment; patients who had already responded to DBS over a year of treatment were those likely to respond to active than sham stimulation in the double-blind randomized phase; findings may not be generalizable to patients with treatment-resistant depression who are DBS-nnaïve.
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2018. Policy statement revised. The key identified literature is summarized below.
 
Primary Dystonia
In 2017, Moro et al published a systematic review of literature published through November 2015 on
primary dystonia (also known as isolated dystonia) (Moro, 2017). Reviewers included studies with at least 10 cases. Fifty-eight articles corresponding to 54 unique studies were identified; most involved bilateral DBS of the GPi. There were only 2 controlled studies, 1 RCT (Volkmann et al; described below) and 1 study that included a double-blind evaluation with and without stimulation. Twenty-four studies reported data using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and were included in a meta-analysis. These studies enrolled a total of 523 patients (mean per study, 22 patients) and had a mean follow-up of 32.3 months (range, 6-72 months). In a pooled analysis of BFMDRS motor scores (scale range, 0-120; higher scores indicate more severe dystonia) from 24 studies, the mean increase in scores at 6 months compared with baseline was 23.8 points (95% CI, 18.5 to 29.1 points). The mean increase in the motor score at last follow-up compared with baseline was 26.6 points (95% CI, 22.4 to 30.9 points). The mean percentage improvement was 59% at 6 months and 65% at last follow-up. Fourteen studies reported BFMDRS disability scores (scale range, 0-30). Compared with baseline, the mean absolute change in the score was 4.8 points (95% CI, 3.1 to 6.6 points) at 6 months and 6.4 points (95% CI, 5.0 to 7.8 points) at last follow-up. The mean percentage improvement was 44% at 6 months and 59% at last follow-up.
 
The RCT, which was an industry-sponsored, patient- and observer-blinded evaluation of pallidal neurostimulation in subjects with refractory cervical dystonia, was published by Volkmann (Volkmann, 2014). The trial included 62 adults with cervical dystonia of at least 3 years in duration, a severity score of at least 15 on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), and an unsatisfactory response to botulinum toxin injection and oral medication. Patients were randomized to DBS (n=32) or to sham stimulation (n=30). The primary outcome was change in the TWSTRS severity score at the end of the blinded study period (3 months); thereafter, all patients received open-label active stimulation. After 3 months, mean TWSTRS score improved by 5.1 points (95% CI, 3.5 to 7.0 points) in the neurostimulation group and by 1.3 points (95% CI, 0.4 to 2.2 points) in the sham group. The between-group difference was 3.8 points (95% CI, 1.8 to 5.8 points; p=0.024). Findings were mixed on the prespecified secondary outcomes. There was significantly greater improvement in the neurostimulation than in the sham group on the TWSTRS disability score and the Bain Tremor Scale score, but not on the TWSTRS pain score or the Craniocervical Dystonia Questionnaire‒24 score. During the 3-month blinded study period, 22 adverse events were reported in 20 (63%) patients in the neurostimulation group and 13 adverse events were reported in 12 (40%) patients in the sham group. Of these 35 adverse events, 11 (31%) were serious. Additionally, 40 adverse events, 5 of which were serious, occurred during 9 months of the open-label extension period. During the study, 7 patients experienced dysarthria (ie, slightly slurred speech), which was not reversible in 6 patients.
 
 
PRACTICE GUIDELINES AND POSITION STATEMENTS
 
European Academy of Neurology
In 2016, the European Academy of Neurology (EAN) published guidelines on neuromodulation in
management of chronic pain (Cruccu, 2016). EAN’s recommendation on deep brain stimulation (DBS) for treatment of neuropathic pain was inconclusive and based on a “very low” quality of evidence.
 
 

CPT/HCPCS:
61850Twist drill or burr hole(s) for implantation of neurostimulator electrodes, cortical
61860Craniectomy or craniotomy for implantation of neurostimulator electrodes, cerebral, cortical
61863Twist drill, burr hole, craniotomy, or craniectomy with stereotactic implantation of neurostimulator electrode array in subcortical site (eg, thalamus, globus pallidus, subthalamic nucleus, periventricular, periaqueductal gray), without use of intraoperative microelectrode recording; first array
61864Twist drill, burr hole, craniotomy, or craniectomy with stereotactic implantation of neurostimulator electrode array in subcortical site (eg, thalamus, globus pallidus, subthalamic nucleus, periventricular, periaqueductal gray), without use of intraoperative microelectrode recording; each additional array (List separately in addition to primary procedure)
61867Twist drill, burr hole, craniotomy, or craniectomy with stereotactic implantation of neurostimulator electrode array in subcortical site (eg, thalamus, globus pallidus, subthalamic nucleus, periventricular, periaqueductal gray), with use of intraoperative microelectrode recording; first array
61868Twist drill, burr hole, craniotomy, or craniectomy with stereotactic implantation of neurostimulator electrode array in subcortical site (eg, thalamus, globus pallidus, subthalamic nucleus, periventricular, periaqueductal gray), with use of intraoperative microelectrode recording; each additional array (List separately in addition to primary procedure)
61880Revision or removal of intracranial neurostimulator electrodes
61885Insertion or replacement of cranial neurostimulator pulse generator or receiver, direct or inductive coupling; with connection to a single electrode array
61886Insertion or replacement of cranial neurostimulator pulse generator or receiver, direct or inductive coupling; with connection to 2 or more electrode arrays
61888Revision or removal of cranial neurostimulator pulse generator or receiver
95836Electrocorticogram from an implanted brain neurostimulator pulse generator/transmitter, including recording, with interpretation and written report, up to 30 days
95970Electronic analysis of implanted neurostimulator pulse generator/transmitter (eg, contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with brain, cranial nerve, spinal cord, peripheral nerve, or sacral nerve, neurostimulator pulse generator/transmitter, without programming
95976Electronic analysis of implanted neurostimulator pulse generator/transmitter (eg, contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with simple cranial nerve neurostimulator pulse generator/transmitter programming by physician or other qualified health care professional
95977Electronic analysis of implanted neurostimulator pulse generator/transmitter (eg, contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with complex cranial nerve neurostimulator pulse generator/transmitter programming by physician or other qualified health care professional
95978Electronic analysis of implanted neurostimulator pulse generator system (eg, rate, pulse amplitude and duration, battery status, electrode selectability and polarity, impedance and patient compliance measurements), complex deep brain neurostimulator pulse generator/transmitter, with initial or subsequent programming; first hour
95979Electronic analysis of implanted neurostimulator pulse generator system (eg, rate, pulse amplitude and duration, battery status, electrode selectability and polarity, impedance and patient compliance measurements), complex deep brain neurostimulator pulse generator/transmitter, with initial or subsequent programming; each additional 30 minutes after first hour (List separately in addition to code for primary procedure)
95983Electronic analysis of implanted neurostimulator pulse generator/transmitter (eg, contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with brain neurostimulator pulse generator/transmitter programming, first 15 minutes face to face time with physician or other qualified health care professional
95984Electronic analysis of implanted neurostimulator pulse generator/transmitter (eg, contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with brain neurostimulator pulse generator/transmitter programming, each additional 15 minutes face to face time with physician or other qualified health care professional (List separately in addition to code for primary procedure)
L8679Implantable neurostimulator, pulse generator, any type
L8680Implantable neurostimulator electrode, each
L8681Patient programmer (external) for use with implantable programmable neurostimulator pulse generator, replacement only
L8682Implantable neurostimulator radiofrequency receiver
L8683Radiofrequency transmitter (external) for use with implantable neurostimulator radiofrequency receiver
L8685Implantable neurostimulator pulse generator, single array, rechargeable, includes extension
L8686Implantable neurostimulator pulse generator, single array, non rechargeable, includes extension
L8687Implantable neurostimulator pulse generator, dual array, rechargeable, includes extension
L8688Implantable neurostimulator pulse generator, dual array, non rechargeable, includes extension

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