Clinical Policy Bulletin: Vagus Nerve Stimulation...treatment. Vagus nerve stimulation (VNS) using the NeuroCybernetic Prosthesis (NCP) System has been shown to shorten the duration

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http://qawww.aetna.com/cpb/medical/data/100_199/0191_draft.html 04/15/2015

Clinical Policy Bulletin: Vagus Nerve Stimulation

Revised February 2015

Number: 0191

Policy

Aetna considers vagus nerve electrical stimulators medically necessary durable medical

equipment (DME) for shortening the duration or reducing the severity of seizures in members

with partial onset seizures who remain refractory to optimal anti-epileptic medications and/or

surgical intervention, or who have debilitating side effects from anti-epileptic medications. (Note:

Electronic analysis of an implanted neurostimulator pulse generator system for vagus nerve

stimulation is considered medically necessary when criteria are met).

Aetna considers transcutaneous vagus nerve stimulation experimental and investigational for the

treatment of seizures and all other indications (see below) because the effectiveness of this

approach has not been established.

Aetna considers vagus nerve electrical stimulators and transcutaneous vagus nerve

stimulation experimental and investigational for the treatment of all other indications because its

effectiveness for these indications has not been established (not an all inclusive list):

Addictions

Anxiety disorders

Autism

Bipolar disorders

Cerebral palsy

Chronic headaches

Cognitive impairment associated with Alzheimer’s disease

Coma

Depression

Eating disorders (e.g., anorexia and bulimia)

Essential tremor

Fibromyalgia

Generalized epilepsy syndromes

Generalized treatment-resistant epilepsy

Heart failure

Hemicrania continua

Impaired glucose tolerance/Pre-diabetes

Juvenile myoclonic epilepsy

Migraine headaches

Mood disorders

Narcolepsy

Obesity

Obsessive-compulsive disorder

http://qawww.aetna.com/cpb/medical/data/100_199/0191_draft.html



Sleep disorder

Stroke

Tinnitus

Tourette's syndrome

Traumatic brain injury (TBI) including post-TBI pneumonia

See also CPB 0221 - Quantitative EEG (Brain Mapping), CPB 0226 - Hospitalization for the

Initiation of Ketogenic Diet for the Treatment of Intractable Seizures, CPB 0279 - Magnetic

Source Imaging/Magnetoencephalography, CPB 0322 - Electroencephalographic (EEG) Video

Monitoring, CPB 0394 - Epilepsy Surgery, CPB 0425 - Ambulatory Electroencephalography, and

CPB 0406 - Tinnitus Treatments.

Background

Approximately 1.7 millions Americans suffer from epilepsy. The vast majority of these patients

can be controlled by conventional drug therapy. Despite the availability of new anti-epileptic

medications and advances in surgical therapy, more than 200,000 people remain refractory to

treatment. Vagus nerve stimulation (VNS) using the NeuroCybernetic Prosthesis (NCP) System

has been shown to shorten the duration and reduce the severity of seizures in certain patients

who remain refractory despite optimal drug therapy or surgical intervention or in those with

debilitating side effects of anti-epileptic medications.

The NCP System, approved by the Food and Drug Administration (FDA) on July 16, 1997, is a

pacer-like device implanted under the skin in the upper left chest area. It is connected by wire to

a lead that is wrapped around the left vagus nerve in the neck. Through the vagus nerve, it

delivers intermittent electrical pulses 24 hours a day to the brain. When a patient senses the

impending onset of a seizure, he/she can activate the device through a hand-held magnet to

deliver an additional dose of stimulation. Treatment with the vagus nerve stimulator is not free of

side effects. Patients have experienced cough, hoarseness, alterations in their voice, and

shortness of breath.

Recent studies have established vagus nerve stimulation to be a viable option for improving

seizure control in difficult to treat pediatric patients with epilepsy (Zamponi et al, 2002; Murphy et

al, 2003; Smyth et al, 2003; and Buoni et al, 2004). An assessment of VNS in children by the

National Institute for Clinical Excellence (NICE, 2004) reached the following conclusion:

"Current evidence on the safety and efficacy of vagus nerve stimulation for refractory epilepsy in

children appears adequate to support the use of this procedure, provided that the normal

arrangements are in place for consent, audit and clinical governance".

It has been reported that VNS in patients with epilepsy is associated with an improvement in

mood. Approximately 1/3 of patients with major depressive disorder fail to experience sufficient

symptom improvement despite adequate treatment. Management of patients with treatment

resistant depression (TRD) usually consists of pharmacological or non-pharmacological

methods. The former approach entails switching to another anti-depressant monotherapy, and

augmentation or combination with 2 or more antidepressants or other agents. The latter

approach includes psychotherapy, electroconvulsive therapy, and VNS. Although VNS is

associated with mood improvements in patients with epilepsy, randomized, controlled studies

with long-term follow-up are needed to confirm its effect on TRD. In this regard, Kosel and

Schlaepfer (2003) stated that recent data from an open-label, multi-center pilot study involving 60

patients (Goodnick et al, 2001) suggested a potential clinical usefulness in the acute and

maintenance treatment of TRD. However, definite therapeutic effects of clinical significance

remain to be confirmed in large placebo-controlled trial. This is in agreement with the

observation of George et al (2000) who noted that additional research is needed to clarify the

mechanisms of action of VNS and its potential clinical utility in the management of patients with

TRD. Because of the lack of well-designed controlled clinical trials, VNS for refractory




depression is considered experimental and investigational. Long-term data regarding tolerability

as well as symptomatic and functional outcomes of depressed patients receiving VNS are

needed to ascertain the effectiveness of this procedure for treating refractory depression. An

assessment by the Institute for Clinical Systems Improvement (ICSI, 2004) stated that VNS for

depression “cannot be considered evidence-based.”

In an acute phase pilot study (n = 59), Nahas et al (2005) evaluated the safety and effectiveness

of VNS for patients with treatment-resistant major depressive episode (MDE). They examined

the effects of adjunctive VNS over 24 months in this patient population. Adult outpatients with

chronic or recurrent major depressive disorder or bipolar (I or II) disorder and experiencing a

treatment-resistant, non-psychotic MDE (DSM-IV criteria) received 2 years of VNS. Changes in

psychotropic medications and VNS stimulus parameters were allowed only after the first 3

months. Response was defined as greater than or equal to 50 % reduction from the baseline 28-

item Hamilton Rating Scale for Depression (HAM-D-28) total score, and remission was defined

as a HAM-D-28 score less than or equal to 10. Based on last observation carried forward

analyses, HAM-D-28 response rates were 31 % (18/59) after 3 months, 44 % (26/59) after 1

year, and 42 % (25/59) after 2 years of adjunctive VNS. Remission rates were 15 % (9/59) at 3

months, 27 % (16/59) at 1 year, and 22 % (13/59) at 2 years. By 2 years, 2 deaths (unrelated to

VNS) had occurred, 4 participants had withdrawn from the study, and 81 % (48/59) were still

receiving VNS. Longer-term VNS was generally well- tolerated. These investigators concluded

that their findings suggest that patients with chronic or recurrent, TRD may show long-term

benefit when treated with VNS.

George et al (2005) stated that previous reports had described the effects of VNS plus treatment

as usual (VNS+TAU) during open trials of patients with TRD. To better understand these effects

on long-term outcome, these researchers compared 12-month VNS+TAU outcomes with those of

a comparable TRD group. Admission criteria were similar for those receiving VNS+TAU (n =

205) or only TAU (n = 124). In the primary analysis, repeated-measures linear regression was

used to compare the VNS+TAU group (monthly data) with the TAU group (quarterly data)

according to scores of the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR

(30)). The 2 groups had similar baseline demographic data, psychiatric and treatment histories,

and degrees of treatment resistance, except that more TAU participants had at least 10 prior

major depressive episodes, and the VNS+TAU group had more electroconvulsive therapy before

study entry. The VNS+TAU group was associated with greater improvement per month in IDS-

SR(30) than the TAU group across 12 months (p < 0.001). Response rates according to the 24-

item Hamilton Rating Scale for Depression (last observation carried forward) at 12 months were

27 % for the VNS+TAU group and 13 % for the TAU group (p < 0.011). Both groups received

similar TAU (drugs and electroconvulsive therapy) during follow-up. These investigators

concluded that this comparison of 2 similar but non-randomized TRD groups showed that

VNS+TAU was associated with a greater anti-depressant benefit over 12 months. These

preliminary findings by Nahas et al (2005) as well as George as et (2005) need to be validated by

prospective, randomized placebo-controlled studies.

In a randomized controlled 10-week study, Rush and colleagues (2005a) compared adjunctive

VNS with sham treatment in 235 outpatients with non-psychotic major depressive disorder (n =

210) or non-psychotic, depressed phase, bipolar disorder (n = 25). Subjects had not responded

adequately to between 2 to 6 research-qualified medication trials. A 2-week, single-blind recovery

period (no stimulation) and then 10 weeks of masked active or sham VNS followed implantation.

Medications were kept stable. Primary efficacy outcome among 222 evaluable participants was

based on response rates (greater than or equal to 50 % reduction from baseline on the 24-item

Hamilton Rating Scale for Depression [HRSD(24)]). At 10-weeks, HRSD(24) response rates

were 15.2 % for the active (n = 112) and 10.0 % for the sham (n = 110) groups (p

= 0.251). Response rates with a secondary outcome, the Inventory of Depressive

Symptomatology - Self-Report (IDS-SR(30)), were 17.0 % (active) and 7.3 % (sham) (p =

0.032). Vagal nerve stimulation was well-tolerated; 1 % (3/235) of subjects left the study

because of adverse events. These investigators concluded that this study did not yield definitive

evidence of short-term effectiveness of adjunctive VNS in TRD.




Rush et al (2005b) described follow-up of outpatients with non-psychotic major depressive (n =

185) or bipolar (I or II) disorder, depressed phase (n = 20) who initially received 10 weeks of

active (n = 110) or sham VNS (n = 95). The initial active group received another 9 months, while

the initial sham group received 12 months of VNS. Participants received anti-depressant

treatments and VNS, both of which could be adjusted. The primary analysis (repeated measures

linear regression) revealed a significant reduction in HRSD(24) scores (average improvement,

.45 points [SE = .05] per month (p < 0.001). At exit, HRSD(24) response rate was 27.2 %

(55/202); remission rate (HRSD(24) less than or equal to 9) was 15.8 % (32/202). Montgomery

Asberg Depression Rating Scale (28.2 % [57/202]) and Clinical Global Impression-Improvement

(34.0 % [68/200]) showed similar response rates. Voice alteration, dyspnea, and neck pain were

the most frequently reported adverse events. These researchers concluded that these 1-year

open trial data found VNS to be well-tolerated, suggesting a potential long-term, growing benefit

in TRD, albeit in the context of changes in depression treatments. Comparative long-term data

are needed to determine whether these benefits can be attributed to VNS.

Furthermore, the BlueCross BlueShield TEC assessment on VNS for TRD (2005) stated that this

method does not meet the TEC criteria. The TEC assessment stated that the available evidence

is insufficient to permit conclusions of the effect of VNS therapy on health outcomes. According

to the TEC assessment, “the available evidence consists of a case series of 60 patients receiving

VNS, a short-term (i.e., 3-month) randomized, sham-controlled clinical trial of 221 patients, and

an observational study comparing 205 patients on VNS therapy compared to 124 patients

receiving ongoing treatment for depression. Patients who responded to sham treatment in the

short-term randomized, controlled trial (approximately 10%) were excluded from the long-term

observational study. Patient selection was a concern for all studies. VNS is intended for

treatment-refractory depression, but the entry criteria of failure of 2 drugs and a 6-week trial of

therapy may not be a strict enough definition of treatment resistance. Treatment-refractory

depression should be defined by thorough state-of-the-art psychiatric evaluation and

management”.

The BlueCross BlueShield Association updated their assessment in August 2006, and concluded

that VNS does not meet the TEC criteria. The assessment explained that, "[s]ince the last TEC

Assessment, there have been no studies reporting clinical outcomes on any new or different

patients. Data from the case series and clinical trials have been reanalyzed to show what

proportions of patients who respond at one time are still responders at a subsequent time point.

However, this information by itself does not provide evidence of the efficacy of VNS beyond that

provided by the original observational comparison of VNS versus treatment as usual."

An assessment of VNS for severe depression by the Aggressive Research Intelligence Facility

(ARIF, 2005) stated: "To conclude, this is an experimental and as yet unproven method of

treatment for severe depression. If this treatment is utilized, patients should be advised of the

experimental nature of the treatment and should be assessed by an expert in the field, who is

familiar with the treatment. The treatment should ideally be given as part of a robust evaluation

of clinical effectiveness and safety in order to add to the current evidence base". Furthermore,

an assessment by the California Technology Assessment Forum (CTAF, 2006) concluded that

the use of VNS for the treatment of resistant depression does not meet CTAF's technology

assessment criteria for safety, effectiveness, and improvement in health outcomes.

George et al (2007) stated that VNS is a new approach in treating neuropsychiatric diseases

within the class of brain-stimulating devices known as neuromodulators. Although VNS has

received FDA approval for the treatment of medication-resistant depression. there is a lack of

Class I evidence of effectiveness in treating depression. The authors concluded that much more

research is needed regarding exactly how to refine and deliver the electrical pulses and how this

differentially affects brain function in health and disease.

The Centers for Medicare & Medicaid Services (CMS, 2007) stated that there is sufficient

evidence to conclude that VNS is not reasonable and necessary for the treatment of resistant




depression. Thus, CMS has announced a national non-coverage determination for this

indication.

In a systematic review on the safety and effectiveness of VNS in the management of patients

with TRD, Daban and colleagues (2008) concluded that VNS seems to be an interesting new

approach to treating TRD. However, despite the promising results reported mainly in open

studies, further clinical trials are necessary to confirm its effectiveness in major depression.

Moreover, studies on its mechanism of action and cost-effectiveness are also needed to better

understand and develop VNS therapy for affective disorder. This is in agreement with the

observation of Fitzgerald and Daskalakis (2008) who stated that given the invasive nature of

VNS and potential side effects, further research on its use for the treatment of depression is

urgently needed. This should include the development of predictors of clinical response and

definition of stimulation parameters with enhanced effectiveness.

An Agency for Healthcare Research and Quality's review (Gaynes et al, 2011) reported that there

is insufficient evidence to evaluate whether non-pharmacological treatments are effective for

TRD. The review summarized evidence of the effectiveness of 4 non-pharmacological

treatments: (i) electroconvulsive therapy (ECT), (ii) repetitive transcranial magnetic stimulation

(rTMS), (iii) VNS, and (iv) cognitive behavioral therapy (CBT) or interpersonal psychotherapy.

With respect to maintaining remission (or preventing relapse), there were no direct comparisons

(evidence) involving ECT, rTMS, VNS, or CBT. With regard to indirect evidence, there were 3

fair trials compared rTMS with a sham procedure and found no significant differences, however,

too few patients were followed during the relapse prevention phases in 2 of the 3 studies (20-

week and 6-month follow-up) and patients in the 3rd study (3-month follow-up) received a co-

intervention providing insufficient evidence for a conclusion. There were no eligible studies for

ECT, VNS. or psychotherapy.

The review concluded that that comparative clinical research on non-pharmacologic interventions

in a TRD population is early in its infancy, and many clinical questions about efficacy and

effectiveness remain unanswered. Interpretation of the data is substantially hindered by varying

definitions of TRD and the paucity of relevant studies. The greatest volume of evidence is for

ECT and rTMS. However, even for the few comparisons of treatments that are supported by

some evidence, the strength of evidence is low for benefits, reflecting low confidence that the

evidence reflects the true effect and indicating that further research is likely to change our

confidence in these findings. This finding of low strength is most notable in 2 cases: ECT and

rTMS did not produce different clinical outcomes in TRD, and ECT produced better outcomes than

pharmacotherapy. No trials directly compared the likelihood of maintaining remission for

non-pharmacologic interventions. The few trials addressing adverse events, subpopulations,

subtypes, and health-related outcomes provided low or insufficient evidence of differences

between non-pharmacologic interventions. The most urgent next steps for research are to apply

a consistent definition of TRD, to conduct more head-to-head clinical trials comparing non-

pharmacologic interventions with themselves and with pharmacologic treatments, and to

delineate carefully the number of treatment failures following a treatment attempt of adequate

dose and duration in the current episode.

Recently, VNS has been used to treat patients with autism, obesity, Alzheimer’s disease, and

obsessive-compulsive disorder. Results from pilot studies suggested that VNS might induce

weight loss in obese individuals and improve cognitive function in patients with Alzheimer’s

disease. However, these findings need to be validated in large randomized placebo-controlled

studies with long-term outcomes.

In an open-label study, Camilleri and associates (2008) evalauted the effects of vagal blocking by

means of a new medical device that uses high-frequency electrical algorithms to create

intermittent vagal blocking (VBLOC therapy) on excess weight loss (EWL). Electrodes were

implanted laparoscopically on both vagi near the esophago-gastric junction to provide electrical

block. Patients (obese subjects with body mass index [BMI] of 35 to 50 kg/m(2)) were followed

for 6 months for body weight, safety, electrocardiogram, dietary intake, satiation, satiety, and

plasma pancreatic polypeptide (PP) response to sham feeding. To specifically assess device




effects alone, no diet or exercise programs were instituted. A total of 31 patients (mean BMI,

41.2 +/- 1.4 kg/m(2)) received the device. Mean EWL at 4 and 12 weeks and 6 months after

implant was 7.5 %, 11.6 %, and 14.2 %, respectively (all p < 0.001); 25 % of patients lost over 25

% EWL at 6 months (maximum, 36.8 %). There were no deaths or device-related serious

adverse events (AEs). Calorie intake decreased by greater than 30 % at 4 and 12 weeks and 6

months (all p < or = 0.01), with earlier satiation (p < 0.001) and reduced hunger (p = 0.005). After

12 weeks, plasma PP responses were suppressed (20 +/- 7 versus 42 +/- 19 pg/ml). Average

percent EWL in patients with PP response less than 25 pg/ml was double that with PP response

greater than 25 pg/ml (p = 0.02). Three patients had serious AEs that required brief

hospitalization, 1 each for lower respiratory tract, subcutaneous implant site seroma, and

clostridium difficile diarrhea. The authors concluded that VBLOC therapy is associated with

significant EWL and a desirable safety profile. They noted that these findings have resulted in

the design and implementation of a randomized, double-blind, prospective, multi-center trial in an

obese subject population.

Vagal nerve stimulation is also being studied for treating chronic headaches; however, its value for

this indication has yet to be established. Mauskop (2005) reported that VNS was implanted in

4 men and 2 women with disabling chronic cluster and migraine headaches. In 1 man and 1

woman with chronic migraines, VNS produced dramatic improvement with restoration of ability to

work. Two patients with chronic cluster headaches had significant improvement of their

headaches. Treatment was well-tolerated in 5 patients, while 1 developed nausea even at the

lowest current strength. The author concluded that VNS may be an effective therapy for

intractable chronic migraine and cluster headaches and deserves further trials.

Ansari et al (2007) noted that a possible role of VNS in the treatment of severe refractory

headache, intractable chronic migraine and cluster headache has been suggested. Clinical trials

are ongoing to examine VNS as a potential treatment for essential tremor, cognitive deficits in

Alzheimer's disease, anxiety disorders, and bulimia. Furthermore, VNS has also been studied in

the treatment of resistant obesity, addictions, sleep disorders, narcolepsy, coma, as well as

memory and learning deficits.

In a review on current and future treatments for chronic migraine, Mathew (2009) stated that

larger and more accurate studies are needed to further evaluate the usefulness of VNS as a

preventive migraine treatment.

In a pilot study, Schwartz et al (2008) examined the feasibility and safety and tested possible

efficacy of chronic VNS in patients with heart failure (HF). A total of 8 patients (mean age of 54

years) were included in this study. CardioFit (BioControl Medical), a vagal

stimulation implantable system delivering pulses synchronous with heart beats through a multiple

contact bipolar cuff electrode, was used. Vagus nerve stimulation was started 2 to 4 weeks after

implant, slowly raising intensity; patients were followed 1, 3 and 6 months thereafter. All

procedures were successful: as sole surgical side effect, 1 patient had transient hoarseness.

Vagal stimulation was well-tolerated, with only mild side effects (cough and sensation of electrical

stimulation). There was a significant improvement in NYHA class, Minnesota quality of life (from

52 +/- 14 to 31 +/- 18, p < 0.001), left ventricular end-systolic volume (from 208 +/- 71 to 190 +/-

83 ml, p = 0.03), and a favorable trend toward reduction in end-diastolic volume. The authors

concluded that this novel approach in treating patients with HF is feasible, and appears safe and

tolerable. They stated that the preliminary efficacy results appear promising, and that these

findings suggest the opportunity to proceed with a larger multi-center study.

Rosenberg et al (2009) stated that treatment of mood disorders is one of the most challenging

territories in the elderly. Effectiveness of different treatment strategies could be related to age,

sex and physical conditions. The side effect profile in this population also affects pharmacological

interventions. These investigators reviewed the neurostimulative treatment strategies in this

population of patients. However, possible treatment strategies such as electroconvulsive

therapy, transcranial magnetic stimulation (TMS), VNS and deep brain stimulation (DBS) were

less studied in the elderly. Electroconvulsive therapy was found to be an

effective treatment procedure in mood disorders. Few double-blind sham controlled studies were




conducted and demonstrated effectiveness of TMS; and DBS has lack of double-blind studies.

Electroconvulsive therapy appears to be the golden standard for the treatment resistant elderly

patients despite its side effects. The authors stated that double-blind, sham, controlled studies

with larger samples are needed to confirm preliminary results with transcranial direct current

stimulation, magnetic seizure therapy, DBS as well as VNS.

Jaseja (2008) stated that cerebral palsy (CP) continues to pose a cause for major socio-

economic concern and medical challenge worldwide. It is associated with a multi-faceted

symptomatology warranting a multi-dimensional management-approach. Recent recognition of

neurocognitive impairment and its hopefully possible treatment has opened up a new dimension

in its management to the neurologists. Vagal nerve stimulation technique is presently emerging

as an effective alternative anti-epileptic therapeutic measure in intractable epilepsy. Vagus nerve

stimulation has recently been shown to possess a suppressive effect also on interictal

epileptiform discharges (IEDs) that are now being widely accepted as established associates of

neurocognitive impairment. The author proposed VNS technique implantation in CP patients on

account of its dual therapeutic effectiveness, i.e., anti-epileptic and IED-suppression. These 2

effects are likely to control seizures that are quite often drug-resistant and also improve

neurocognition in CP patients, thus hoping for a better overall prognostic outcome and an

improved quality of life of the CP patients by VNS.

Kraus et al (2007) stated that direct VNS has proved to be an effective treatment for seizure

disorder. However, since this invasive technique implies surgery, with its side-effects and

relatively high financial costs, a non-invasive method to stimulate vagal afferences would be a

great step forward. These researchers studied effects of non-invasive electrical stimulation of

the nerves in the left outer auditory canal in healthy subjects (n = 22), aiming to activate vagal

afferences transcutaneously (tVNS). Short-term changes in brain activation and subjective well-

being induced by tVNS were investigated by functional magnetic resonance imaging (fMRI) and

psychometric assessment using the adjective mood scale (AMS), a self-rating scale for current

subjective feeling. Stimulation of the ear lobe served as a sham control. Functional MRI showed

that robust tVNS induced blood oxygenation level dependent (BOLD)-signal decreases in limbic

brain areas, including the amygdala, hippocampus, para-hippocampal gyrus and the middle and

superior temporal gyrus. Increased activation was seen in the insula, precentral gyrus and the

thalamus. Psychometric assessment revealed significant improvement of well-being after tVNS.

Ear lobe stimulation as a sham control intervention did not show similar effects in either fMRI or

psychometric assessment. No significant effects on heart rate, blood pressure or peripheral

microcirculation could be detected during the stimulation procedure. The authors concluded that

these findings showed the feasibility and beneficial effects of tVNS in the left auditory canal of

healthy subjects.

Dietrich and colleagues (2008) stated that left cervical VNS using the implanted NCP can reduce

epileptic seizures. To address a disadvantage of this device, the use of an alternative

transcutaneous electrical nerve stimulation technique, designed for muscular stimulation, was

studied. Functional MRI has been used to test non-invasively access nerve structures

associated with the vagus nerve system. The results and their impact were unsatisfying due to

missing brainstem activations. These activations, however, are mandatory for reasoning, higher

subcortical and cortical activations of vagus nerve structures. The objective of this study was to

test a new parameter setting and a novel device for performing specific tVNS at the inner side of

the tragus. This study showed the feasibility of these and their potential for brainstem and

cerebral activations as measured by BOLD fMRI. In total, 4 healthy male adults were scanned

inside a 1.5-Tesla MR scanner while undergoing tVNS at the left tragus. These investigators

ensured that their newly developed tVNS stimulator was adapted to be an MRI-safe stimulation

device. In the experiment, cortical and brainstem representations during tVNS were compared to

a baseline. A positive BOLD response was detected during stimulation in brain areas associated

with higher order relay nuclei of vagal afferent pathways, the left locus coeruleus, the thalamus,

the left prefrontal cortex, the right and the left postcentral gyrus, the left posterior cingulated

gyrus and the left insula, respectively. Deactivations were found in the right nucleus accumbens




and the right cerebellar hemisphere. The authors concluded that this method and device are

feasible and appropriate for accessing cerebral vagus nerve structures.

Xiong et al (2009) stated that post-operative cognitive dysfunction (POCD) is a decline in cognitive

function for weeks or months after surgery. It may affect the patients' length of hospital stay,

quality of life, the rehabilitation process, and work performance. Prolonged POCD occurs

frequently after cardiac surgery, and the risk of POCD increases with age. The pathophysiology

of POCD is not well-understood. However, emerging evidences indicate that various inflammatory

mediators are involved in the pathophysiology of POCD and inflammatory response may be a

potential pathogenic factor. Vagus nerve stimulation has been shown to decrease production and

release of pro-inflammatory cytokines through the cholinergic anti-inflammatory pathway (CAP) in

both animal model and human. Considering that inflammation plays a definite role in the

pathogenesis of POCD and the vagus nerve can mediate inflammation via CAP, these

researchers hypothesized that transcutaneous VNS may attenuate POCD by reducing

inflammatory response in elderly patients.

Hemicrania continua is a rare, relentless, constant, 1-sided headache that is accompanied at

times by mild symptoms related to dysfunction of the autonomic nervous system in the face --

small pupil, drooping eyelid, red or watering eye, stuffy or runny nose -- similar to the symptoms of

a cluster headache, but much less dramatic. The pain is usually dull but can wax and wane in

severity. These headaches often subside entirely with prescription anti-inflammatory medication.

Magis et al (2011) stated that cluster headache is well known as one of the most painful primary

neurovascular headache. Since 1 % of chronic cluster headache patients become refractory to

all existing pharmacological treatments, various invasive and sometimes mutilating procedures

have been tried in the last decades. Recently, neurostimulational approaches have raised new

hope for drug-resistant chronic cluster headache patients. The authors reviwed the evidence on

stimulation of the great occipital nerve, which has been the best evaluated peripheral nerve

stimulation technique in drug-resistant chronic cluster headache, providing the most convincing

results so far. Other peripheral nerve stimulation approaches used for this indication were also

reviewed in detail. They noted that "[a]lthough available studies are limited to a relatively small

number of patients and placebo-controlled trials are lacking .... More studies are needed to

evaluate the usefulness of supraorbital nerve stimulation and of vagus nerve stimulation in

management of cluster headaches".

Martin and Martin-Sanchez (2012) evaluated the effectiveness of VNS for treatment of

depression. These researchers conducted a systematic review and meta-analysis of analytical

studies. Effectiveness was evaluated according to severity of illness and percentage of

responders. They identified 687 references. Of these, 14 met the selection criteria and were

included in the review. The meta-analysis of effectiveness for uncontrolled studies showed a

significant reduction in scores at the Hamilton Depression Rating Scale endpoint, and the

percentage of responders was 31.8 % ([23.2 % to 41.8 %], p < 0.001). However, the randomized

controlled trial that covered a sample of 235 patients with depression, reported no statistically

significant differences between the active intervention and placebo groups (odds ratio [OR] =

1.61 [95 % confidence interval [CI]: 0.72 to 3.62]; p = 0.25). To study the cause of this

heterogeneity, a meta-regression was performed. The adjusted co-efficient of determination (R2

(Adj)) was 0.84, which implies that an 84 % variation in effect size across the studies was

explained by baseline severity of depression (p < 0.0001). The authors concluded that currently,

insufficient data are available to describe VNS as effective in the treatment of depression. In

addition, it cannot be ruled out that the positive results observed in the uncontrolled studies might

have been mainly due to a placebo effect.

In a pilot study, Lehtimaki et al (2013) examined if transcutaneous VNS (tVNS) combined with

sound therapy (ST) would reduce the severity of tinnitus and tinnitus-associated distress. The

objectives were to study whether tVNS has therapeutic effects on patients with tinnitus and,

additionally, if tVNS has effects on acoustically evoked neuronal activity of the auditory cortex.

The clinical efficacy was studied by a short-term tVNS plus ST trial in 10 patients with tinnitus

using disease-specific and general well-being questionnaires. Transcutaneous VNS was




delivered to the left tragus. The acute effects of tVNS were evaluated in 8 patients in the MEG

study in which the N1m response was analyzed in terms of source level amplitude and latency in

the presence or absence of tVNS. The treatment with tVNS plus ST produced improved mood

and decreased tinnitus handicap scores, indicating reduced tinnitus severity. The application of

tVNS decreased the amplitude of auditory N1m responses in both hemispheres. The results of

this pilot study need to be validated by well-designed studies.

Straube et al (2012) stated that chronic migraine (CM) was first defined in the second edition of

the International Headache Society (IHS) classification in 2004. The definition currently used

(IHS 2006) requires the patient to have headache on more than 15 days/month for longer than 3

months and a migraine headache on at least 8 of these monthly headache days and that there is

no medication overuse. In daily practice the majority of the patients with CM also report

medication overuse but it is difficult to determine whether the use is the cause or the

consequence of CM. Most the patients also have other co-morbidities, such as depression,

anxiety and chronic pain at other locations. Therapy has to take this complexity into

consideration and is generally multi-modal with behavioral therapy, aerobic training and

pharmacotherapy. The use of analgesics should be limited to fewer than 15 days per month and

use of triptans to fewer than 10 days per month. Drug treatment should be started with

topiramate, the drug with the best scientific evidence. If there is no benefit, onabotulinum toxin A

(155 to 195 Units) should be used. There is also some limited evidence that valproic acid and

amitriptyline might be beneficial. Moreover, the authors stated that neuromodulation by

stimulation of the greater occipital nerve or vagal nerve is being tested in studies and is so far an

experimental procedure only.

On behalf of the Guideline Development Subcommittee of the American Academy of Neurology

(AAN), Morris et al (2013) evaluated the evidence since the 1999 assessment regarding safety

and effectiveness of (VNS for epilepsy, currently approved as adjunctive therapy for partial-onset

seizures in patients greater than 12 years of age. These investigators reviewed the literature and

identified relevant published studies. They classified these studies according to the AAN

evidence-based methodology. Vagal nerve stimulation is associated with a greater than 50 %

seizure reduction in 55 % (95 % CI: 50 % to 59 %) of 470 children with partial or generalized

epilepsy (13 Class III studies). Vagal nerve stimulation is associated with a greater than 50 %

seizure reduction in 55 % (95 % CI: 46 % to 64 %) of 113 patients with Lennox-Gastaut

syndrome (LGS) (4 Class III studies). Vagal nerve stimulation is associated with an increase in

greater than or equal to 50% seizure frequency reduction rates of approximately 7 % from 1 to 5

years post-implantation (2 Class III studies). Vagal nerve stimulation is associated with a

significant improvement in standard mood scales in 31 adults with epilepsy (2 Class III studies).

Infection risk at the VNS implantation site in children is increased relative to that in adults (OR =

3.4, 95 % CI: 1.0 to 11.2). Vagal nerve stimulation is possibly effective for seizures (both partial

and generalized) in children, for LGS-associated seizures, and for mood problems in adults with

epilepsy; it may have improved efficacy over time. The authors concluded that VNS may be

considered for seizures in children, for LGS-associated seizures, and for improving mood in

adults with epilepsy (Level C); it may be considered to have improved efficacy over time (Level

C). Children should be carefully monitored for site infection after VNS implantation. Moreover,

these researchers noted that some reports have discussed VNS use in small numbers of patients

with juvenile myoclonic epilepsy (JME); they stated that larger reports would help substantiate

whether VNS is appropriate in medically refractory JME.

McClelland et al (2013) stated that eating disorders (ED) are chronic and sometimes deadly

illnesses. Existing treatments have limited proven efficacy, especially in the case of adults with

anorexia nervosa. Emerging neural models of ED provide a rationale for more targeted, brain-

directed interventions. In a systematic review, these investigators examined the effects of

neuromodulation techniques on eating behaviors and body weight and assessed their potential

for therapeutic use in ED. All articles in PubMed, PsychInfo and Web of Knowledge were

considered and screened against a priori inclusion/exclusion criteria. The effects of repetitive

transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, VNS and deep

brain stimulation (DBS) were examined across studies in ED samples, other psychiatric and




neurological disorders, and animal models. A total of 60 studies were identified. There is

evidence for ED symptom reduction following rTMS and DBS in both anorexia nervosa and

bulimia nervosa. Findings from studies of other psychiatric and neurological disorders and from

animal studies demonstrated that increases in food intake and body weight can be achieved

following DBS and that VNS has potential value as a means of controlling eating and inducing

weight loss. The authors concluded that neuromodulatory tools have potential for reducing ED

symptomatology and related behaviors, and for altering food intake and body weight. They

stated that more research is needed to evaluate the potential of neuromodulatory procedures for

improving long-term outcomes in ED.

Elliott et al (2011a) evaluated the safety and effectiveness of VNS in a consecutive series of

adults and children with treatment-resistant epilepsy (TRE). In this retrospective review of a

prospectively created database of 436 consecutive patients who underwent VNS implantation for

TRE between November 1997 and April 2008, there were 220 (50.5 %) females and 216 (49.5

%) males ranging in age from 1 to 76 years at the time of implantation (mean of 29.0 ± 16.5).

Thirty-three patients (7.6 %) in the primary implantation group had inadequate follow-up (less

than 3 months from implantation) and 3 patients had early device removal because of infection

and were excluded from seizure control outcome analyses. Duration of VNS treatment varied

from 10 days to 11 years (mean of 4.94 years). Mean seizure frequency significantly improved

following implantation (mean reduction of 55.8 %, p < 0.0001). Seizure control greater than or

equal to 90 % was achieved in 90 patients (22.5 %), greater than or equal to 75 % seizure control

in 162 patients (40.5 %), greater than or equal to 50 % improvement in 255 patients (63.75 %),

and less than 50 % improvement in 145 patients (36.25 %). Permanent injury to the vagus nerve

occurred in 2.8 % of patients. The authors concluded that VNS is a safe and effective palliative

treatment option for focal and generalized TRE in adults and children. When used in conjunction

with a multi-disciplinary and multi-modality treatment regimen including aggressive anti-epileptic

drug regimens and epilepsy surgery when appropriate, more than 60 %

of patients with TRE experienced at least a 50 % reduction in seizure burden. Good results were

seen in patients with non FDA-approved indications. Moreover, they stated that prospective,

randomized trials are needed for patients with generalized epilepsies and for younger children to

potentially expand the number of patients who may benefit from this palliative treatment. The

authors also noted the following drawbacks of the study: (i) although patients were entered

prospectively into the database, this study was performed via retrospective query. Follow-up

was unavailable in 8 % of patients, providing a small margin of error in the estimates of VNS

efficacy. Determination of seizure frequency and use and efficacy of magnetic swiping relied on

the report of patients or caretakers and is inherently subject to error, (ii) a design limitation

inherent to all retrospective, non-randomized studies on VNS is the lack of a control group, and

(iii) a potential confound is the effect of AED (anti-epileptic drug) regimen changes on seizure

frequency over time in the setting of VNS. Many office visits were accompanied by VNS setting

changes and, much more frequently, by AED regimen adjustments (medication and/or dosage

changes). The complexity and frequency of such changes (often multiple changes in a single

visit) proved too difficult to incorporate into a meaningful analysis. The authors could not control

for all of these changes but believe AED treatment plays a major role in the success of any

treatment plan that includes long-term VNS therapy. In fact, the increase in VNS efficacy over

time reported by numerous centers may be due to alteration in device parameters, changes in

AED regimen, or an undefined, synergistic effect of both.

Elliott et al (2011b) analyzed the effectiveness of VNS in a large consecutive series of children

18 years of age and younger with TRE and compared the safety and effectiveness in children

under 12 years of age with the outcomes in older children. These researchers retrospectively

reviewed 141 consecutive cases involving children (75 girls and 66 boys) with TRE in whom

primary VNS implantation was performed by the senior author between November 1997 and

April 2008 and who had at least 1 year of follow-up since implantation. The patients' mean age

at VNS insertion was 11.1 years (range of 1 to 18 years). Eighty-six children (61.0 %) were

younger than 12 years at time of VNS insertion (which constitutes off-label usage of this device).

Follow-up was complete for 91.8 % of patients and the mean duration of VNS therapy in these

patients was 5.2 years (range of 25 days to 11.4 years). Seizure frequency significantly




improved with VNS therapy (mean reduction of 58.9 %, p < 0.0001) without a significant reduction

in anti-epileptic medication burden (median number of anti-epileptic drugs taken 3, unchanged).

Reduction in seizure frequency of at least 50 % occurred in 64.8 % of patients and

41.4 % of patients experienced at least a 75 % reduction. Major (3) and minor (6) complications

occurred in 9 patients (6.4 %) and included 1 deep infection requiring device removal, 1

pneumothorax, 2 superficial infections treated with antibiotics, 1 seroma/hematoma treated with

aspiration, persistent cough in 1 patient, severe but transient neck pain in 1 patient, and

hoarseness in 2 patients. There was no difference in efficacy or complications between children

12 years of age and older (FDA-approved indication) and those younger than 12 years of age (off

-label usage). Linear regression analyses did not identify any demographic and clinical variables

that predicted response to VNS. The authors concluded that VNS is a safe and effective

treatment for TRE in young adults and children. Over 50 % of patients experienced at least 50 %

reduction in seizure burden. Children younger than 12 years had a response similar to that of

older children with no increase in complications. Moreover, they stated that given the efficacy of

this device and the devastating effects of persistent epilepsy during critical developmental

epochs, randomized trials are needed to potentially expand the indications for VNS to include

younger children. Moreover, the authors stated that this study was limited by the retrospective

query into a prospective database and was subject to biases inherent to such methodology.

Nearly 8 % of patients were unavailable for follow-up. Determination of seizure frequency relied

on the reports of patients or caretakers and is inherently subject to error and bias. This limitation

is common to many studies measuring seizure frequency and treatment outcomes. These

researchers tried to improve their estimates by using LVCF (last value carried forward) analysis

instead of declining-n analysis, which is prone to non-responder attrition. Detailed information on

the effects of VNS on mood, quality of life, and qualitative aspects of seizures (duration, severity,

clustering, postictal period, and magnet usage) were either not systematically reported or could

not be derived from this retrospective analysis. Moreover, these investigators did not determine

if a mean reduction in seizures of nearly 50 % translates into caretaker and patient satisfaction

and overall improvements in quality of life. They stated that future prospective studies are needed

to better ascertain baseline mood assessments, quality-of-life metrics, and caretaker satisfaction

and to determine the impact of VNS on these parameters and their relation to seizure control.

Another confound concerns the unknown impact that changes in AED regimens have on seizure

frequency over time in the setting of VNS. Many office visits were accompanied by VNS setting

changes and, more frequently, by AED regimen adjustments. The authors could not control for

these changes but believe AED treatment plays a major role in the success of any treatment plan,

including long-term VNS therapy. They stated that further study is needed to better understand

the relative contributions of effective VNS therapy, AED regimen adjustments,

and regression to the mean.

The study by Elliott et al (2011b) (effects of VNS on children) appeared to be a sub-analysis of

the study by Elliott et al 2011a) (effects of VNS on adults and children).

An UpToDate review on “Vagus nerve stimulation therapy for the treatment of epilepsy” (Karceski

and Schachter, 2014) states that “The Food and Drug Administration (FDA) has approved vagus

nerve stimulator (VNS) therapy as adjunctive treatment for adults and adolescents over 12 years

of age whose partial-onset seizures were refractory to antiepileptic drugs. Since the approval of

VNS therapy for epilepsy, clinicians have actively debated its role. While further controlled

studies are needed to more fully understand the safety, tolerability, and efficacy profile of VNS in

children and in patients with generalized seizures, VNS is often used in these cases as well ….

Case series suggest that VNS is also effective in generalized epilepsy syndromes. While some

studies found that symptomatic generalized epilepsy is more responsive to VNS than idiopathic

syndromes, others have reported the opposite or found no difference”.

Huang et al (2014) noted that impaired glucose tolerance (IGT) is a pre-diabetic state of

hyperglycemia that is associated with insulin resistance, increased risk of type II diabetes, and

cardiovascular pathology. Recently, investigators hypothesized that decreased vagus nerve

activity may be the underlying mechanism of metabolic syndrome including obesity, elevated

glucose levels, and high blood pressure (BP). In this pilot randomized clinical trial (RCT), these




researchers compared the effectiveness of transcutaneous auricular VNS (taVNS) and sham-

taVNS on patients with IGT. A total of 72 participants with IGT were single-blinded and were

randomly allocated by computer-generated envelope to either taVNS or sham-taVNS treatment

groups. In addition, 30 IGT adults were recruited as a control population and not assigned

treatment so as to monitor the natural fluctuation of glucose tolerance in IGT patients. All

treatments were self-administered by the patients at home after training at the hospital. Patients

were instructed to fill in a patient diary booklet each day to describe any side effects after each

treatment. The treatment period was 12 weeks in duration. Baseline comparison between

treatment and control group showed no difference in weight, BMI, or measures of systolic BP,

diastolic BP, fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), or glycosylated

hemoglobin (HbAlc). A total of 100 participants completed the study and were included in data

analysis. Two female patients (1 in the taVNS group, 1 in the sham-taVNS group) dropped out of

the study due to stimulation-evoked dizziness. The symptoms were relieved after stopping

treatment. Compared with sham-taVNS, taVNS significantly reduced the 2-hour glucose tolerance

(F(2) = 5.79, p = 0.004). In addition, these investigators found that taVNS significantly decreased

(F(1) = 4.21, p = 0.044) systolic BP over time compared with sham-taVNS. Compared with the no-

treatment control group, patients receiving taVNS significantly differed in measures of FPG (F(2) =

10.62, p < 0.001), 2hPG F(2) = 25.18, p < 0.001) and HbAlc (F(1) = 12.79, p = 0.001) over the

course of the 12-week treatment period. The authors concluded that the findings of this study

suggested that taVNS is a promising, simple, and cost-effective treatment for IGT/ pre-

diabetes with only slight risk of mild side-effects.

Cai et l (2014) stated that because of its ability to regulate mechanisms well-studied in

neuroscience, such as norepinephrine and serotonin release, the vagus nerve may play an

important role in regulating cerebral blood flow, edema, inflammation, glutamate excito-toxicity,

and neurotrophic processes. There is strong evidence that these same processes are important

in stroke pathophysiology. These investigators reviewed the literature for the role of VNS in

improving ischemic stroke outcomes by performing a systematic search for publications in Medline

(1966 to 2014) with keywords "VNS AND stroke" in subject headings and key words with no

language restrictions. Of the 73 publications retrieved, these researchers identified 7 studies from

3 different research groups that met the final inclusion criteria of research studies

addressing the role of VNS in ischemic stroke. Results from these studies suggested that VNS

has promising efficacy in reducing stroke volume and attenuating neurological deficits in

ischemic stroke models. Given the lack of success in phase III trials for stroke neuroprotection, it

is important to develop new therapies targeting different neuroprotective pathways. The authors

concluded that further studies of the possible role of VNS, through normally physiologically active

mechanisms, in ischemic stroke therapeutics should be conducted in both animal models and

clinical studies. In addition, recent advent of a non-invasive, transcutaneous VNS could provide

the potential for easier clinical translation.

Hall et al (2104) stated that nosocomial infections, pneumonia in particular, are well-known

complications of traumatic brain injury (TBI), which are associated with a worse neurological

outcome. These researchers explored the role of vagus nerve activity in immunomodulation as a

causative factor. A MEDLINE search revealed numerous reports published over the last decade

describing the "cholinergic anti-inflammatory pathway" between the vagus nucleus and leukocyte

activity. Using a combination of lipopolysaccharide stimulation and vagotomy, it has been shown

that the parasympathetic fibers terminating in the spleen reduce tumor necrosis factor (TNF)

production. Further pharmacological and receptor knockout studies have identified the α7 subtype

of nicotinic receptors as the likely target for this. Vagal activity also induces changes in neutrophil

chemotaxis through altered expression of the CD11b integrin which is abolished by splenectomy.

By extrapolating this evidence these investigators suggested a possible mechanism for

immunosuppression following TBI, which also has the potential to be targeted to reduce the

incidence of pneumonia. The authors concluded that while there is strong supporting evidence for

the role of vagal nerve over-activity in post-TBI pneumonia, there have yet to be any clinical

investigations and further study is needed.




Zhou et al (2014) noted that previous studies have shown that VNS can improve the prognosis of

TBI. These researchers examined the mechanism of the neuroprotective effects of VNS in rabbits

with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10

V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin

(IL)-1β and IL-10 concentrations were detected in serum and brain tissues, and water content in

brain tissues was measured. Results showed that VNS could reduce the degree of brain edema,

decrease TNF-α and IL-1β concentrations, and increase IL-10 concentration after brain explosive

injury in rabbits. The authors concluded that these data suggested that VNS may exert

neuroprotective effects against explosive injury via regulating the

expression of TNF-α, IL-1β and IL-10 in the serum and brain tissue.

Howland (2014) noted that right cervical VNS is effective for treating heart failure in pre-clinical

studies and a phase II clinical trial. The effectiveness of various forms of non-invasive

transcutaneous VNS for epilepsy, depression, primary headaches, and other conditions has not

been investigated beyond small pilot studies. The relationship between depression,

inflammation, metabolic syndrome, and heart disease might be mediated by the vagus nerve.

The author concluded that VNS deserves further study for its potentially favorable effects on

cardiovascular, cerebrovascular, metabolic, and other physiological biomarkers associated with

depression morbidity and mortality.

Appendix

Exclusion Criteria for VNS Therapy of Partial Onset Seizures:

VNS can not be used in persons with left or bilateral cervical vagotomy

VNS is not indicated for persons with other types of seizures.

CPT Codes / HCPCS Codes / ICD-9 Codes

CPT codes covered if selection criteria are met:

61885 Insertion or replacement of cranial neurostimulator pulse generator or

receiver, direct or inductive coupling; with connection to a single electrode

array

64553 Percutaneous implantation of neurostimulator electrode array; cranial

nerve

64568 Incision for implantation of cranial nerve (eg, vagus nerve) neurostimulator

electrode array and pulse generator

64569 Revision or replacement of cranial nerve (eg, vagus nerve)

neurostimulator electrode array, including connection to existing pulse

generator

64570 Removal of cranial nerve (eg, vagus nerve) neurostimulator electrode

array and pulse generator

95970 Electronic analysis of implanted neurostimulator pulse generator system

(e.g., rate, pulse amplitude and duration, configuration of wave form,

battery status, electrode selectability, output modulation, cycling,

impedance and patient compliance measurements); simple or complex

brain, spinal cord, or peripheral (i.e., cranial nerve, peripheral nerve, sacral

nerve, neuromuscular) neurostimulator pulse generator/transmitter,

without reprogramming




95974 complex cranial nerve neurostimulator pulse generator/transmitter, with

intraoperative or subsequent programming, with or without nerve interface

testing, first hour

+ 95975 complex cranial nerve neurostimulator pulse generator/transmitter, with

intraoperative or subsequent programming, each additional 30 minutes

after first hour (List separately in addition to code for primary procedure)

CPT codes not covered for indications listed in the CPB:

0312T Vagus nerve blocking therapy (morbid obesity); laparoscopic implantation

of neurostimulator electrode array, anterior and posterior vagal trunks

adjacent to esophagogastric junction (EGJ), with implantation of pulse

generator, includes programming

0313T Vagus nerve blocking therapy (morbid obesity); laparoscopic revision or

replacement of vagal trunk neurostimulator electrode array, including

connection to existing pulse generator

0317T Vagus nerve blocking therapy (morbid obesity); neurostimulator pulse

generator electronic analysis, includes reprogramming when performed

64550 Application of surface (transcutaneous) neurostimulator [not covered for

transcutaneous vagus nerve stimulation]

Other CPT codes related to the CPB:

0314T Vagus nerve blocking therapy (morbid obesity); laparoscopic removal of

vagal trunk neurostimulator electrode array and pulse generator

0315T Vagus nerve blocking therapy (morbid obesity); removal of pulse generator

0316T Vagus nerve blocking therapy (morbid obesity); replacement of pulse

generator

HCPCS codes covered if selection criteria are met:

C1767 Generator, neurostimulator (implantable), nonrechargeable

C1778 Lead, neurostimulator (implantable)

C1816 Receiver and/or transmitter, neurostimulator (implantable)

C1883 Adaptor/ extension, pacing lead or neurostimulator lead (implantable)

L8680 Implantable neurostimulator electrode, each

L8681 Patient programmer (external) for use with implantable programmable

neurostimulator pulse generator, replacement only

L8682 Implantable neurostimulator radiofrequency receiver

L8683 Radiofrequency transmitter (external) for use with implantable

neurostimulator radiofrequency receiver

L8685 Implantable neurostimulator pulse generator, single array, rechargeable,

includes extension

L8686 Implantable neurostimulator pulse generator, single array, non-

rechargeable, includes extension




L8687 Implantable neurostimulator pulse generator, dual array, rechargeable,

includes extension

L8688 Implantable neurostimulator pulse generator, dual array, non-

rechargeable, includes extension

L8689 External recharging system for battery (internal) for use with implanted

neurostimulator, replacement only

L8695 External recharging system for battery (external) for use with implantable

neurostimulator, replacement only

ICD-9 codes covered if selection criteria are met:

345.40 - 345.41 Localization-related (focal) (partial) epilepsy and epileptic syndromes with

complex partial seizures [not covered for transcutaneous vagus nerve

stimulation]

345.50 - 345.51 Localization-related (focal) (partial) epilepsy and epileptic syndromes with

simple partial seizures [not covered for trancutaneous vagus nerve

stimulation]

ICD-9 codes not covered for indications listed in the CPB:

278.00 - 278.01 Obesity

291.82 Alcohol-induced sleep disorders

292.85 Drug-induced sleep disorders

296.00 - 296.99 Episodic mood disorders

298.0 Depressive type psychosis

299.00 - 299.01 Autistic disorder

300.00 - 300.09 Anxiety states

300.3 Obsessive-compulsive disorders

300.4 Dysthymic disorder

301.11 Chronic hypomanic personality disorder

303.00 - 303.93 Alcohol dependence syndrome

304.00 - 304.93 Drug dependence

305.00 - 305.93 Nondependent abuse of drugs

307.1 Anorexia nervosa

307.23 Tourette's disorder

307.40 - 307.49 Specific disorders of sleep of nonorganic origin

307.50 - 307.59 Other and unspecified disorders of eating

307.81 Tension headache

311 Depressive disorder, not elsewhere classified

327.19 Other organic hypersomnia




327.30 - 327.39 Circadian rhythm sleep disorder

327.40 - 327.49 Organic parasomnia

327.51 - 327.59 Organic sleep related movement disorders

327.8 Other organic sleep disorders

331.0 Alzheimer's disease

333.1 Essential and other specified forms of tremor

339.10 Tension type headache, unspecified

339.41 Hemicrania continua

343.0 - 343.9 Infantile cerebral palsy

345.00 - 345.3

345.60 - 345.91

Epilepsy [other than partial onset]

346.00 - 346.93 Migraine

347.00 - 347.11 Cataplexy and narcolepsy

388.30 - 388.32 Tinnitus

398.91 Rheumatic heart failure (congestive)

402.01 Hypertensive heart disease, malignant, with heart failure

402.11 Hypertensive heart disease, benign, with heart failure

402.91 Hypertensive heart disease, unspecified, with heart failure

404.01 Hypertensive heart and chronic kidney disease, malignant, with heart

failure and with chronic kidney disease stage I through stage IV, or

unspecified

404.03 Hypertensive heart and chronic kidney disease, malignant, with heart

failure and chronic kidney disease stage V or end stage renal disease

404.11 Hypertensive heart and chronic kidney disease, benign, with heart failure

and with chronic kidney disease stage I through stage IV, or unspecified

404.13 Hypertensive heart and chronic kidney disease, benign, with heart failure

and chronic kidney disease stage V or end stage renal disease

404.91 Hypertensive heart and chronic kidney disease, unspecified, with heart

failure and with chronic kidney disease stage I through stage IV, or

unspecified

404.93 Hypertensive heart and chronic kidney disease, unspecified, with heart

failure and chronic kidney disease stage V or end stage renal disease

428.0 - 428.9 Heart failure

729.1 Myalgia and myositis, unspecified [fibromyalgia]

780.01 Coma

780.39 Other convulsions [seizure NOS]




780.50 - 780.59 Sleep disturbances

783.6 Polyphagia

784.0 Headache

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Clinical Policy Bulletin: Vagus Nerve Stimulation...treatment. Vagus nerve stimulation (VNS) using the NeuroCybernetic Prosthesis (NCP) System has been shown to shorten the duration