Surgery Section - Deep Brain Stimulation for Movement Disorders and Miscellaneous Conditions

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

Deep brain stimulation (DBS) has been investigated as an alternative to permanent neuroablative procedures, such as thalamotomy and pallidotomy. (For further discussion of the neuroablative procedures see Surgery Policy No. 32. Stereotactic Radiofrequency Surgery for the Treatment of Parkinson's Disease) The technique has been most thoroughly investigated as an alternative to thalamotomy for unilateral control of essential tremor, and tremor associated with Parkinson's disease (PD). More recently, there has been research interest in the use of deep brain stimulation of the globus pallidus or subthalamic nucleus (STN) as a treatment of other Parkinsonian symptoms, such as rigidity, bradykinesia or akinesia. Another common morbidity associated with PD is the occurrence of motor fluctuations, referred to as "on and off" phenomena, related to the maximum effectiveness of drugs (i.e., the "on" state) and the nadir response during drug troughs (i.e., the "off" state). In addition, levodopa, the most commonly used antiparkinson drug, may be associated with disabling drug-induced dyskinesias. Therefore, the optimal pharmacologic treatment of Parkinson's disease may involve a balance between optimal effects on Parkinson's symptoms vs. the appearance of drug induced dyskinesias. The effect of DBS on both Parkinson's symptoms and drug-induced dyskinesias has also been studied.

DBS has also been investigated in patients with primary dystonia, defined as a neurological movement disorder characterized by involuntary muscle contractions, which force certain parts of the body into abnormal, contorted, and painful movements or postures. Dystonia can be classified according to age of onset, bodily distribution of symptoms, and cause. Age of onset can occur during childhood or during adulthood. Dystonia can affect certain portions of the body (focal dystonia and multifocal dystonia) or the entire body (generalized dystonia). Torticollis is an example of a focal dystonia. Primary dystonia is defined when dystonia is the only symptom unassociated with other pathology. Treatment options for dystonia include oral or injectable medications (i.e., botulinum toxin) and destructive surgical or neurosurgical interventions (i.e., thalamotomies or pallidotomies) when conservative therapies fail.

In addition, DBS has been recently investigated for intractable epilepsy, cluster headaches, chronic intractable pain, morbid obesity and psychiatric disorders such as obsessive-compulsive disorder.

In addition, DBS has been recently investigated in patients with chronic cluster headaches. Cluster headaches occur as episodic attacks of severe pain lasting from 30 minutes to several hours. The pain is usually unilateral and localized to the eye, temple, forehead, and side of the face. Autonomic symptoms that occur with cluster headaches include ipsilateral facial sweating, flushing, tearing, and rhinorrhea. Cluster headaches occur primarily in men and have been classified as vascular headaches that have been associated with high blood pressure, smoking, and alcohol use. However, the exact pathogenesis of cluster headaches is uncertain. PET scanning and MRI have shown the hypothalamic region may be important in the pathogenesis of cluster headaches. Alterations in hormonal/serotonergic function may also play a role. Treatment of cluster headaches includes pharmacologic interventions for acute episodes and prophylaxis, sphenopalatine ganglion (SPG) blockade and surgical procedures such as percutaneous SPG radiofrequency rhizotomy and gamma knife radiosurgery of the trigeminal nerve.

Deep brain stimulation involves the stereotactic placement of an electrode into the brain (i.e., thalamus, globus pallidus or STN). 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 more severe symptoms. However, the use of bilateral stimulation using two electrode arrays is also used 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's 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.

At the present time, there is only one device that has been approved by the US Food and Drug Administration (FDA) for deep brain stimulation: the Activa® Tremor Control System, manufactured by Medtronic Corp., MN. While the original 1997 FDA labeled indications were limited to unilateral implantation of the device for the treatment of tremor, in January 2002, the FDA-labeled indications were expanded to include bilateral implantation as a treatment to decrease the symptoms of advanced Parkinson’s that are not controlled by medication. In April 2003, the labeled indications were 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.” This latter indication received FDA approval through the Humanitarian Device Exemption process.

The Activa® Tremor Control System and the Activa® Dystonia Therapy System consist of the following components:

1. The implantable pulse generator
2. The deep brain stimulator lead
3. An extension that connects the lead to the power source
4. A console programmer
5. A software cartridge to set electrical parameters for simulation
6. A patient control magnet, which allows the patient to turn the pulse generator on and off or change between high and low settings

Note: The use of spinal cord stimulation as a treatment of chronic pain is addressed in a separate policy, Surgery Policy No. 45, Spinal Cord Stimulation for Treatment of Pain.

Policy/Criteria

1. When a multidisciplinary evaluation has confirmed both the medical intractability of the patient's symptoms and the potential value of deep brain stimulation (DBS), unilateral or bilateral DBS may be considered medically necessary for:


1. Stimulation of the thalamus in patients with disabling, medically unresponsive tremor due to essential tremor, multiple sclerosis, or Parkinson's disease.
2. Stimulation of the subthalamic nucleus (STN) or globus pallidus in patients with previously levodopa-responsive Parkinson's disease and symptoms such as rigidity, bradykinesia, dystonia or levodopa-induced dyskinesias.
3. Stimulation of the STN or globus pallidus in patients seven years of age or above with disabling, medically unresponsive primary dystonias including generalized and/or segmental dystonia, hemidystonia and cervical dystonia (torticollis).


2. Disabling, medically unresponsive tremor or dystonia is defined as all of the following:


1. Tremor or dystonia causing significant limitation in daily activities
2. Inadequate symptom control despite optimal medical management for at least 3 months before implant


3. Contraindications to deep brain stimulation include:


1. Patients who are not good surgical risks because of comorbid medical problems or because of the presence of a cardiac pacemaker
2. Patients who have medical conditions that require repeated MRI
3. Patients who have dementia that may interfere with the ability to cooperate


4. Deep brain stimulation is considered investigational for other conditions, including but not limited to the following:


1. Other movement disorders
2. Post-traumatic tremor
3. Cluster headaches
4. Chronic pain (e.g., neuropathic pain)
5. Morbid obesity
6. Epilepsy
   

Position Summary

The policy is based in part on two TEC Assessments; a 1997 TEC Assessment that focused on unilateral deep brain stimulation of the thalamus as a treatment for tremor (2) and a 2001 TEC Assessment that focused on the use of deep brain stimulation of the globus pallidus and subthalamic nucleus for a broader range of Parkinson symptoms. (3)  The observations and conclusions of the TEC assessment are summarized below.  Articles published since these two assessments continue to report positive outcomes for deep brain stimulation for tremor and Parkinson’s disease.

Unilateral Deep Brain Stimulation of the Thalamus for Tremor (2)

Outcome from TEC Assessment:

• Tremor suppression was total or clinically significant in 82% to 91% of operated sides in 179 patients who underwent implantation of thalamic stimulation devices. Results were durable for up to eight 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 Deep Brain Stimulation of the Globus Pallidus or Subthalamic Nucleus (3)

Outcome from TEC Assessment:

• 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 six to twelve 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 poses advantages to other treatment options. In comparison to pallidotomy, deep brain stimulation can be performed bilaterally. The procedure is non-ablative and reversible.

Additional Published Literature:

A Review of literature 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). (12) 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.

Deep Brain Stimulation for the Treatment of Primary Dystonia

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 affect 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.  A search of the literature for DBS with a focus on primary dystonias identified three studies that reported at least ten cases. Clinical improvement ranged from 50 to 88%. A total of twenty-one pediatric patients were studied; 81% were older than seven years. Among these patients there was approximately a 60% improvement in clinical scores. As noted in the FDA’s analysis of risk and probable benefit, the only other treatment options for chronic refractory primary dystonias 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 onset of dystonia occurs prior to the individual reaching their full adult size, the disease not only can affect normal psychological 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.” (4)

Since the FDA approval there have been additional published trials of DBS for dystonia which continue to report positive results. (5,6) 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 one 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.

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). (15) Blinded assessment with the Burke-Fahn-Marsden Dystonia Rating Scale found improvements in the movement score (16 points vs. 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 vs. 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.

Other Conditions

There is interest in applications of DBS beyond that for essential tremors and Parkinson’s disease. (7) Clinical trials are being pursued; however, at this time, FDA approval is limited to the above indications.

An updated search of the MEDLINE database failed to identify any published clinical trials related to the use of DBS for the treatment of post-traumatic tremors or morbid obesity.  Currently, the bulk of the published studies related to DBS for other conditions consist of small, non-randomized, uncontrolled, short-term trials which do not permit scientific conclusions related to health outcomes.

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 Leone and colleagues 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. (8-10)  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. Stimulation of the posterior hypothalamus was reported to have completely resolved headache in 10 of 16 chronic cluster headache patients and in 1 patient with neuralgiform headache; treatment failed in 3 of 3 patients who had atypical facial pain. (17)

DBS for the treatment of chronic pain was investigated and largely abandoned in the 1980’s due to poor results in two trials.  With improved technology and surgical techniques there has been a recent resurgence of interest in DBS for intractable pain.  For example, Owen and colleagues studied DBS of the periventricular/periaqueductal grey area (PVG/PAG) and sensory thalamus for treatment of post-stroke neuropathic pain. (11) Twelve patients were studied for an average follow-up of 27 months, achieving an average pain relief of 40-50%.  Seven patients stopped all analgesics and five patients changed from regular opiate analgesia to “as required” non-opiates.  The authors note that pain relief varied markedly between patients and that this variability along with the small number of patients in the study make it difficult to reach conclusions.

DBS has been investigated for the treatment of intractable seizures in patients who are not surgical candidates.  To date studies show promise but these early reports of therapeutic success are not confirmed by controlled clinical trials.  Question regarding the best structures to stimulate, the most effective stimuli, and the contrasting effects of high-frequency and low-frequency stimulation remain unanswered. 

Stimulation of the globus pallidus has been examined as a treatment of tardive dyskinesia in a phase II double-blinded (presence and absence of stimulation) multicenter study. (16) 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. 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. (18) Evidence remains insufficient to evaluate the efficacy of deep brain stimulation for these disorders.

References

1. BlueCross and BlueShield Association Medical Policy Reference Manual, Policy No. 7.01.63
2. TEC Assessment; Deep Brain Stimulation of the Thalamus for Tremor, 1997 (tab 20); BlueCross and BlueShield Association Technology Evaluation Center
3. TEC Assessment; Bilateral Deep Brain Stimulation of the Subthalamic Nucleus or the Globus Pallidus Interns for Treatment of Advanced Parkinson's Disease, 2001 (tab 16); BlueCross and BlueShield Association Technology Evaluation Center
4. FDA Summary of Safety and Probable Benefit: Medtronic Activa Dystonia Therapy at www.fda.gov/cdrh/pdf2/H020007b.pdf   (Verified  7/23/08)
5. Halbig TD, Gruber D, Kopp UA et al. Pallidal stimulation in dystonia: effects on cognition, mood and quality of life. J Neurol Neurosurg Psychiatry 2005;76(12):1713-6
6. Vidailhet M, Vercueil L, Houeto JL et al. Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. N Engl J Med 2005;352(5):459-67
7. Grady MS. What’s new in neurological surgery. J Am Coll Surg 2004;199(1):109-13
8. Franzini A, Ferroli P, Leone M et al. Stimulation of the posterior hypothalamus for treatment of chronic intractable cluster headaches: first reported series. Neurosurgery 2003;52(5):1095
9. Leone M, May A, Franzini A et al. Deep brain stimulation for intractable chronic cluster headache: proposals for patient selection. Cephalalgia 2004;24(11):934-7
10. Franzini A, Ferroli P, Leone M et al. Hypothalamic deep brain stimulation for the treatment of chronic cluster headaches: a series report. Neuromodulation 2004;7(1):1-8
11. Owen SLF, Green AL, Stein JF et al.  Deep brain stimulation for the alleviation of post-stroke neuropathic pain. Pain 2006;120(1-2):202-6
12. Kleiner-Fisman G, Herzog J, Fisman DN et al. Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord 2006; 21(suppl 14):S290-304
13. Deuschl G, Schade-Brittinger C, Krack P et al.; German Parkinson Study Group, Neurostimulation Section. A randomized trial of deep-brain stimulation for Parkinson's disease.N Engl J Med 2006; 355(9):896-908
14. Schupbach WM, Maltete D, Houeto JL et al. Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial. Neurology 2007; 68(4):267-71
15. Kupsch A, Benecke R, Muller J et al. Deep-Brain Stimulation for Dystonia Study Group. Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N Engl J Med 2006; 355(19):1978-90
16. Damier P, Thobois S, Witjas T et al; French Stimulation for Tardive Dyskinesia (STARDYS) Study Group. Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia. Arch Gen Psychiatry 2007; 64(2):170-6
17. Broggi G, Franzini A, Leone M et al. Update on neurosurgical treatment of chronic trigeminal autonomic cephalalgias and atypical facial pain with deep brain stimulation of posterior hypothalamus: results and comments. Neurol Sci 2007; 28(suppl 2):S138-45
18. www.ClinicalTrials.gov

Cross References

Spinal Cord Stimulation for Treatment of Pain, Regence Medical Policy Manual, Surgery, Policy No. 45

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