DBS Neurology Brochure

DBS Therapy for Parkinson’s Disease

Perry C.Benefiting from DBS Therapy since 2006

ACHIEVEDaily Victories

HELP YOUR PATIENTS

Deep Brain Stimulation Therapy for Movement Disorders2

• In the United States, there are more than 1 million people living with Parkinson’s disease (PD). 2

• Levodopa generally provides smooth and stable benefits for up to 5 years after therapy introduction.3

• After this period, patients may experience increasingly troublesome and unpredictable motor fluctuations and dyskinesias.3

Motor fluctuations and dyskinesias decrease quality of life for people with Parkinson’s disease1

Iris C.Benefiting from DBS Therapy since 2008

• The delayed “on,” wearing off, and dose failure of levodopa may be due to its impaired absorption, short half-life, and the loss of striatal dopamine storage capacity.3

• When drugs become less reliable, Medtronic DBS Therapy (Deep Brain Stimulation) should be considered to achieve PD treatment goals.

Treating motor fluctuations and dyskinesias requires moving beyond standard dopamine replacement therapy3

Medications Alone Medtronic DBS Therapy

0 hours of additional “on” time4 5.1 hours additional “on” time

without troubling dyskinesias*

Unpredictable More predictable

Dyskinesias and nonmotor side effects

Medication reduction may lead to fewer drug-induced side effects

Pulsatile delivery Continuous delivery

GI absorption required No GI absorption

Must cross blood-brain barrier Targeted and direct

Dosing compliance challenges Simplified medication regimen may be possible

Benefits of Adding Medtronic DBS Therapy

*Mean results; DBS is adjunctive to medications.

Help Your Patients Achieve Daily Victories 3

More than 75,000 patients globally have been treated with Medtronic DBS Therapy.

How Medtronic DBS Therapy Works• One or more leads are implanted to deliver electrical

stimulation to parts of the brain involved in movement control, including the globus pallidus or subthalamic nucleus.

• Current delivered by the lead is believed to disrupt and modulate abnormal motor circuit activity in the brain caused by PD, thereby smoothing out motor function. However, the exact mechanism of action isn’t completely understood.

* This chart is for illustrative purposes and does not reflect actual “on” or “off” time.

DBS Therapy with Medications Provides an Additional 5.1 Hours of “On” Time to Smooth Out Motor Function Throughout the Day4

Time (daily)

“Off” time

“On” time without dyskinesias

Dyskinesias

Without DBS Therapy

With DBS Therapy

“Medicine and surgery are not separate disciplines. Surgery is not the failure of neurology, but rather the extension of neurology.” — George Plotkin, MD, PhD

When drugs become less reliable, Medtronic DBS Therapy should be considered


5.1 hours of additional “on” time without dyskinesias compared to Best Medical Therapy (BMT) alone4

Best Medical Therapy DefinedPatients who received BMT were managed actively by movement disorder neurologists. Patients received state-of-the-art care, including the active management of medications and nonpharmacological therapy (e.g., physical occupational, and speech therapy) as needed to achieve best symptom control.

• Results from prospective multi-center randomized control trial of patients with advanced PD4

• Medications were reduced 25% on average for patients receiving DBS Therapy4

In a Separate Clinical Study, Medtronic DBS Therapy Was Shown to Maintain Symptom Improvements After 5 Years6

BMT Alone(n = 118)

p < 0.001

0 hours

* Results were at 6 months post implant versus baseline.4

Mean Additional Hours of “On” Time Without Dyskinesias

DBS Therapy + BMT

(n = 108)

0 1 2 3 4 5 6

5.1 hours

Additional “On” Time Without Dyskinesias4

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-DBS

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100

80

60

40

20

0Rigidity

73% 74% 71%

Tremor

75%

83%

75%

Akinesia

63%

52% 49%

1 Year (n = 43)

3 Years (n = 42)

5 Years (n = 42)

p < 0.001 5 years after surgery versus baseline

Improvement in Motor Scores After 5 Years

5 Help Your Patients Achieve Daily Victories

• Although there was a significantly higher incidence of serious adverse events observed in patients receiving DBS Therapy, 99% of serious adverse events were resolved by 6 months.4

• Improvements in MRI imaging, stereotactic equipment and software, and patient selection have all helped advance DBS Therapy since the FDA first approved it in 1997.

Surgical risks include:• Infection

• Cerebral hemorrhage

Hardware related risks include: • Lead fractures

Stimulation related side effects include: • Paresthesia

• Speech

• Dystonia

Note: Stimulation-related side effects typically can be reduced or resolved noninvasively through fine-tuning of programming settings.

The majority of serious adverse events* with Medtronic DBS Therapy are procedure-related and temporary4

Proven safety profile

Additional risks and side effects:• Speech may get worse after DBS Therapy,

requiring speech therapy.

• Some risks associated with DBS Therapy may be due to improved function and greater activity.5

Unlike thalamotomy: • DBS Therapy preserves brain structures for

future therapies and treatments.

• DBS Therapy is safely performed bilaterally.4

* A serious adverse event was defined according to FDA regulations as any event that: results in death, is life-threatening, results in prolonged or new hospitalization, results in disability or congenital anomaly/birth defect, or requires medical or surgical intervention to prevent one of the above outcomes.

Note: Adverse events vary depending on implanting centers. Consult with the implanting center you refer patients to in order to determine risks and adverse events.


In order to obtain maximum benefits from DBS Therapy, patients with idiopathic Parkinson’s disease must be referred at the optimal time, or during a “window of opportunity” when the therapy may be most effective.

According to the American Academy of Neurology (AAN), “10% to 20% of people with PD may be eligible for surgical treatments.”7

• No longer responsive to dopaminergic medication• Severely disabled even in the best “on” state

• Medical conditions that prevent surgery• Onset of frank dementia

Patient is experiencing troubling motor symptoms not effectively controlled

by medications.

• “On” time characterized by disabling dyskinesias (or other nonmotor side effects)

OR

• “Off” time characterized by disabling tremor, rigidity, or akinesia/bradykinesia

OR

• Unpredictable “on/off” motor fluctuations

OR

• Medication-resistant tremor

Window of Opportunity

DBS Therapy Exclusion Criteria

Medtronic DBS Therapy in the PD continuum of care


When is Medtronic DBS Therapy appropriate?

Medtronic DBS Patient Referral Advisor The Patient Referral Advisor is a software tool that creates a patient “appropriateness” profile for DBS Therapy based on 5 absolute criteria and 7 relative criteria.

To download the Patient Referral Advisor software visit: www.medtronic.com/dbsreferraladvisor.

DBS Therapy should be considered when the patient, despite optimal medical therapy, reaches a stage where the daily burden of PD begins to cause significant interference with:

• Daily function

• Occupational activities

• Important leisure time pursuits

• Basic activities of daily living

Discuss each patient’s goals and expectations to determine whether DBS Therapy is right for him or her. It’s important to set realistic goals about the benefits of Medtronic DBS Therapy.


Establish a partnership with your Medtronic DBS Therapy implant center to manage postimplant patient care, which involves programming and medical management.

• Initial Device Programming—Identifying and programing optimal stimulation parameters during the first several months

• Maintenance Device Programming—Titrating stimulation as needed over time

Patient programming is reimbursed.

Patient managementMedtronic provides comprehensive education, training, and clinical and technical support to help manage patients with DBS Therapy.

Medtronic has developed technology to make device programming easier, including:

• A step-by-step process that provides a systematic approach to programming

• The ability to capture, store and sort patient data in the device

• Features that maximize therapeutic response and device longevity

Innovative programming software


Present and future neuromodulation therapies

• Today, more than 500,000 patients globally have received Medtronic neuromodulation devices.9

• The future of neurology will include the integration of device-based neuromodulation treatment into the management of the most common neurological disorders.

A paradigm shift DBS Therapy continues to be the fastest growing treatment option for people suffering from movement disorders.

PRESENT FUTURE

Intracerebroventricular (ICV) Applications

Obsessive-Compulsive Disorder*

Chronic Pain (Opioid)

Malignant Pain

Spasticity

Chronic Pain

Parkinson’s Disease

Essential Tremor

Dystonia*

Chronic Migraine (ONS)

Chronic Pain (Nonopioid)

Depression

Urinary Incontinence and Retention

Medtronic neuromodulation therapies

* HumanitarianDevice: The effectiveness of this device for the treatment of dystonia or obsessive-compulsive disorder has not been demonstrated.

Medtronic: The leader in DBS Therapy

Product innovation• Providing new products such as Activa® PC—the next generation primary cell neurostimulator—and

Activa® RC—the first rechargeable neurostimulator for DBS Therapy

• New programming platform provides step-by-step guidance and advanced device programming options

Education• Customized courses for clinicians designed to make DBS Therapy successful in your practice

Procedure support• Medtronic Procedure Solutions provides a complete system to plan, record, place and manage with success

Innovative clinical research• Medtronic has sponsored numerous studies to evaluate the safety and efficacy of DBS for current and

future indications

Medtronic is committed to advancing the science of neuromodulation through:

Kristin E.Benefiting from DBS Therapy since 2003

Indications for DBS Therapy

Parkinson’s Disease

Essential Tremor• AAN Guidelines concluded that unilateral deep

brain stimulation resulted in a significant (60% to 90%) reduction of contralateral limb tremor.8

• DBS Therapy improves activities of daily living in patients with ET.4

Dystonia• Approved in 2003 under Humanitarian Device

Exemption (HDE) for the treatment of dystonia.*

Obsessive-Compulsive Disorder• Approved in 2009 under HDE for the treatment

of obsessive-compulsive disorder.*

* Humanitarian Device: The effectiveness of this device for the treatment of dystonia or obsessive-compulsive disorder has not been demonstrated.

Help Your Patients Achieve Daily Victories 11

Medtronic DBS Therapy for Parkinson’s Disease, Tremor and Dystonia: Patients should always discuss the potential risks and benefits with a physician.Indications: Medtronic DBS Therapy for Parkinson’s Disease: Bilateral stimulation of the internal globus pallidus (GPi) or the subthalamic nucleus (STN) using Medtronic DBS Therapy for Parkinson’s Disease is indicated for adjunctive therapy in reducing some of the symptoms of advanced, levodopa-responsive Parkinson’s disease that are not adequately controlled with medication.

Medtronic DBS Therapy for Tremor: Unilateral thalamic stimulation using Medtronic DBS Therapy for Tremor is indicated for the suppression of tremor in the upper extremity. The system is intended for use in patients who are diagnosed with Essential Tremor or Parkinsonian tremor not adequately controlled by medications and where the tremor constitutes a significant functional disability. The safety or effectiveness of this therapy has not been established for bilateral stimulation.

Medtronic DBS Therapy for Dystonia: Unilateral or bilateral stimulation of the internal globus pallidus (GPi) or the subthalamic nucleus (STN) using Medtronic DBS Therapy for Dystonia is indicated as an aid in the management of chronic, intractable (drug refractory) primary dystonia, including generalized and segmental dystonia, hemidystonia, and cervical dystonia (torticollis), for individuals 7 years of age and older.

Contraindications: Contraindications include patients who will be exposed to MRI using a full body radio-frequency (RF) coil or a head transmit coil that extends over the chest area, patients who are unable to properly operate the neurostimulator, or for Parkinson’s disease and Essential Tremor, patients for whom test stimulation is unsuccessful. Also, diathermy (e.g., shortwave diathermy, microwave diathermy or therapeutic ultrasound diathermy) is contraindicated because diathermy’s energy can be transferred through the implanted system (or any of the separate implanted components), which can cause neurostimulation system or tissue damage and can result in severe injury or death. Transcranial Magnetic Stimulation (TMS) is contraindicated for patients with an implanted DBS System.

Warnings/ Precautions/Adverse Events: There is a potential risk of tissue damage using stimulation parameter settings of high amplitudes and wide pulse widths. Extreme care should be used with lead implantation in patients with a heightened risk of intracranial hemorrhage. The lead-extension connector should not be placed in the soft tissues of the neck due to an increased incidence of lead fracture. Theft detectors and security screening devices may cause stimulation to switch ON or OFF, and may cause some patients to experience a momentary increase in perceived stimulation. Although some MRI procedures can be performed safely with an implanted DBS System, clinicians should carefully weigh the decision to use MRI in patients with an implanted DBS System. MRI can cause induced voltages in the neurostimulator and/or lead possibly causing uncomfortable, jolting, or shocking levels of stimulation.

The DBS System may be affected by or adversely affect medical equipment such as cardiac pacemakers or therapies, cardioverter/ defibrillators, external defibrillators, ultrasonic equipment, electrocautery, or radiation therapy. Safety and effectiveness has not been established for patients with neurological disease other than Parkinson’s disease or Essential Tremor, previous surgical ablation procedures, dementia, coagulopathies, or moderate to severe depression; or for patients who are pregnant, under 18 years, over 75 years of age (Parkinson’s Control Therapy) or over 80 years of age (Tremor Control Therapy). For patients with Dystonia, age of implant is suggested to be that at which brain growth is approximately 90% complete or above. Depression, suicidal ideations and suicide have been reported in patients receiving Medtronic DBS Therapy for Movement Disorders, although no direct cause and effect relationship has been established.

Abrupt cessation of stimulation should be avoided as it may cause a return of disease symptoms, in some cases with an intensity greater than was experienced prior to system implant (“rebound” effect). Adverse events related to the therapy, device, or procedure can include: stimulation not effective, cognitive disorders, pain, dyskinesia, dystonia, speech disorders including dysarthria, infection, paresthesia, intracranial hemorrhage, electromagnetic interference, cardiovascular events, visual disturbances, sensory disturbances, device migration, paresis/asthenia, abnormal gait, incoordination, headaches, lead repositioning, thinking abnormal, device explant, hemiplegia, lead fracture, seizures, respiratory events, and shocking or jolting stimulation.

Humanitarian Device (Dystonia): Authorized by Federal Law for the use as an aid in the management of chronic, intractable (drug refractory) primary dystonia, including generalized and segmental dystonia, hemidystonia, and cervical dystonia (torticollis), for individuals 7 years of age and older. The effectiveness of this device for this use has not been demonstrated. USA Rx only Rev 0311

Reclaim™ Deep Brain Stimulation Therapy for Obsessive-Compulsive Disorder: Product labeling must be reviewed prior to use for detailed disclosure of risks.Indications: The Medtronic Reclaim DBS Therapy is indicated for bilateral stimulation of the anterior limb of the internal capsule, AIC, as an adjunct to medications and as an alternative to anterior capsulotomy for treatment of chronic, severe, treatment-resistant obsessive-compulsive disorder (OCD) in adult patients who have failed at least three selective serotonin reuptake inhibitors (SSRIs).

Contraindications: Contraindications include patients who will be exposed to MRI using a full body radio-frequency (RF) coil or a head transmit coil that extends over the chest area, and for patients who are unable to properly operate the neurostimulator. Also, diathermy (e.g., shortwave diathermy, microwave diathermy or therapeutic ultrasound diathermy) is contraindicated because diathermy’s energy can be transferred through the implanted system (or any of the separate implanted components), which can cause tissue damage and can result in severe injury or death. Diathermy can damage parts of the neurostimulation system. Transcranial Magnetic Stimulation (TMS) is contraindicated for patients with an implanted DBS System.

Warnings/precautions/adverse events:

Electroconvulsive Therapy (ECT) – The safety of ECT in patients who have an implanted deep brain stimulation (DBS) system has not been established. Induced electrical currents may interfere with the intended stimulation or damage the neurostimulation system components resulting in loss of therapeutic effect, clinically significant undesirable stimulation effects, additional surgery for system explantation and replacement, or neurological injury.

There is a potential risk of tissue damage using stimulation parameter settings of high amplitudes and wide pulse widths. Extreme care should be used with lead implantation in patients with a heightened risk of intracranial hemorrhage. Do not place the lead-extension connector in the soft tissues of the neck. Placement in this location has been associated with an increased incidence of lead fracture. Theft detectors and security screening devices may cause stimulation to switch ON or OFF, and may cause some patients to experience a momentary increase in perceived stimulation. Severe burns could result if the neurostimulator case is ruptured or pierced. The safety of somatic psychiatric therapies using equipment that generates electromagnetic interference (e.g., vagus nerve stimulation) has not been established. The Reclaim DBS System may be affected by or adversely affect medical equipment such as cardiac pacemakers or therapies, cardioverter/ defibrillators, external defibrillators, ultrasonic equipment, electrocautery, or radiation therapy. Patients should be monitored for at least 30 minutes after a programming session, for side effects, including: autonomic effects (e.g., facial flushing, facial muscle contractions, or increased heart rate), hypomania, increased disease symptoms, sensations such as tingling, smell, or taste. In addition, during treatment, patients should be monitored closely for increased depression, anxiety, suicidality, and worsening of obsessive-compulsive symptoms. The safety and probable benefit of this therapy has not been established for patients with: Tourette’s syndrome, OCD with a subclassification of hoarding, previous surgical ablation (e.g., capsulotomy), dementia, coagulopathies or who are on anticoagulant therapy, neurological disorders, and other serious medical illness including cardiovascular disease, renal or hepatic failure, and diabetes mellitus. In addition, the safety and probable benefit has not been established for these patients: those whose diagnosis of OCD is documented to be less than 5 years duration or whose YBOCS score is less then 30, who have not completed a minimum of 3 adequate trials of first and/or second line medications with augmentation, who have not attempted to complete an adequate trial of cognitive behavior therapy (CBT), who are pregnant, under the age of 18 years, and who do not have comorbid depression and anxiety. Physicians should carefully consider the potential risks of implanting the Reclaim DBS System in patients with comorbid psychiatric disorders (e.g., bipolar, body dysmorphic, psychotic) as the Reclaim DBS System may aggravate the symptoms. Additionally, the abrupt cessation of stimulation for any reason should be avoided as it may cause a return or worsening (i.e., “rebound” effect) of disease symptoms. Serious adverse events related to the therapy, device, or procedure can include: suicidality/increased depression, increased OCD/fluctuating results, intracranial hemorrhage, lead/extension failure, aggression/violent behavior, accident proneness, irritability, death, hypomania, infection, pyelonephritis, and post-operative seizure. Adverse events related to the therapy, device, or procedure can include: coma, paralysis, pain or discomfort at incision/implant sites, general post-op discomfort, GI symptom (post op), increased anxiety, insomnia, cognitive disturbance (clouding), induced muscle contraction, restlessness, stimulation induced paresthesia, device migration, shocking or jolting stimulation, induced sensation of taste/smell, weight gain, increased fatigue, upper respiratory infection, headaches, dizziness, dry mouth, itching at surgical site(s), nausea, sedation, and weight loss.

Humanitarian Device: Authorized by Federal (U.S.A) law for use as an adjunct to medications and as alternative to anterior capsulotomy for treatment of chronic, severe, treatment-resistant obsessive-compulsive disorder (OCD) in adult patients who have failed at least three selective serotonin reuptake inhibitors (SSRIs). The effectiveness of this device for this use has not been demonstrated. USA Rx Only Rev 1009

References1. Adler, CH. Relevance of motor complications in Parkinson’s disesae. Neurology. 2002;58(Suppl 1):S51-S56.

2. National Parkinson’s Foundation (www.parkinson.org/Page.aspx?pid=225) accessed site, Dec. 3, 2009.

3. Melamed E, Ziv I, Djaldetti R. Management of Motor Control Complications in Advanced Parkinson’s Disease. Movement Disorders. 2007;22(Suppl. 17)S379-S384.

4. Activa Therapy Clinical Summary, 2009.

5. Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson’s disease: a randomized controlled trial. JAMA. 2009;301(1):63-73.

6. Krack R, Batir A, Van Blercom N, et al. Five-Year Follow-up of Bilateral Stimulation of the Subthalamic Nucleus in Advanced Parkinson’s Disease. N Engl J Med. 2003;349:1925-34.

7. AAN Guidelines Summary for patients and their families: medical and surgical treatment for motor fluctuations and dyskinesia in Parkinson’s disease, April 2006.

8. Zesiewicz TA, Elble R, Louis ED, et al. Practice paramater: therapies for essential tremor: Report of the Quality Standards Subcommittee of the AAN. Neurology. 2005;64:2008-2020.

9. Medtronic, Inc. data on file.

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Medtronic Neuromodulation 710 Medtronic Parkway Minneapolis, MN 55432-5604 USA Tel. 763-505-5000 Toll-free 1-800-328-0810

EuropeMedtronic International Trading Sàrl Route du Molliau 31 Case Postale CH-1131 Tolochenaz Switzerland Tel. +41-21-802-7000

Asia-PacificMedtronic International, Ltd. Suite 1602 16/F Manulife Plaza The Lee Gardens, 33 Hysan Avenue Causeway Bay Hong Kong Tel. 852-2891-4456

AustraliaMedtronic Australasia Pty. Ltd. 97 Waterloo Road North Ryde NSW 2113 Australia Tel. +61-2-9857-9000 www.medtronicneuro.com.au

CanadaMedtronic of Canada Ltd. 6733 Kitimat Road Mississauga, Ontario L5N 1W3 Canada Tel. 1-905-826-6020

professional.medtronic.com

Ensure that Medtronic DBS Therapy is a successful part of your practiceStep 1. Partner with your local implanting team.• Establish referral processes and communications.

• Establish postimplant patient management roles.

Step 2. Identify appropriate patients. • Attend a Medtronic education program to learn more about appropriate patient selection.

• Use the DBS Therapy Patient Referral Advisor to confirm appropriateness for patient referral.

Step 3. Discuss DBS Therapy with patients and their caregivers.• Discuss patients’ goals with them.

• Educate patients about the benefits and risks of DBS Therapy.

• Set appropriate expectations.

Step 4. Refer appropriate patients for DBS Therapy.

Documents

DBS Neurology Brochure