Deep Brain Stimulation Therapy for Parkinson

1
Deep Brain StimulationTherapy for
ParkinsonsDisease
Perry C. Benefiting from DBS Therapy since 2007
2
Motor Fluctuations and Dyskinesias Decrease
Quality of Life for People with Parkinsons
Disease1

• In the United States more than 1 million people
  living with Parkinsons disease (PD)2
• Levodopa generally provides smooth and stable
  benefits for up to 5 years3
• After this period, patients may experience
  increasingly troublesome and unpredictable motor
  fluctuations and dyskinesias3

• Adler, CH. Relevance of motor complications in
  Parkinsons disease. Neurology. 200258(Suppl
  1)S51-S56.
• National Parkinsons Foundation
  (www.parkinson.org/Page.aspx?pid225) accessed
  site, Dec. 3, 2009.
• Melamed E, Ziv I, Djaldetti R. Management of
  Motor Control Complications in Advanced
  Parkinson's Disease. Movement Disorders,
  200722(Suppl. 17)S379-S384.

3
Treating motor fluctuations and dyskinesias
requires moving beyond standard dopamine
replacement therapy3

• 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 capacity3
• When drugs become less reliable, Medtronic DBS
  Therapy (Deep Brain Stimulation) should be
  considered to achieve PD treatment goals
• According to the American Academy of Neurology
  (AAN), 10 to 20 of people with PD may be
  eligible for surgical treatments4

3. Melamed E, Ziv I, Djaldetti R. Management of
Motor Control Complications in Advanced
Parkinsons Disease. Movement Disorders.
200722(Suppl. 17)S379-S384. 4. AAN Guidelines
for patients and their families medical and
surgical treatment for motor fluctuations and
dyskenisias in Parkinsons disease. April, 2006.
4
How Does Medtronic DBS Therapy Work?

• One or 2 leads are implanted to deliver
  electrical stimulation to parts of the brain
  involved in movement control, including the
  globus pallidus (GPi) or subthalamic nucleus
  (STN)
• Current delivered by the lead is believed to
  disrupt and modulate abnormal motor circuit
  activity inthe brain caused by PD, thereby
  smoothing out motor function
• The exact mechanism of action isnt completely
  understood

5
Medtronic DBS Therapy with Medications Provides
an Additional 5.1 Hours of On Time to Smooth
Out Motor Function Throughout the Day5
5. Activa Therapy Clinical Summary, 2009.
This chart is for illustrative purposes and
does not reflect actual on or off time.
6
5.1 Hours of Additional On time Without
Dyskinesias Compared to Best Medical Therapy
(BMT)5

• Medications werereduced 25 on average for
  patients receivingDBS Therapy5
• Results from prospective multicenter randomized
  control trial of patients with advanced PD5

Best Medical Therapy Defined Patients who
received BMT were managed actively by movement
disorder neurologists. Patients received
state-of-the-art care, including the active
management of medications and non-pharmacological
therapy (e.g., physical occupational, and speech
therapy) as needed to achieve best symptom
control.
5. Activa Therapy Clinical Summary, 2009.
7
In a Separate Study, DBS Therapy Was Shown to
Maintain Symptom Improvements After 5 Years6
6. Krack R, Batir A, Van Blercom N, et al.
Five-Year Follow-up of Bilateral Stimulation of
the Subthalamic Nucleus in Advanced Parkinsons
Disease. N Engl J Med. 20033491925-34.
8
Proven Safety Profile

• Improvements in MRI imaging, stereotactic
  equipment and software, and patient selection
  have all helped advanceDBS Therapy since the FDA
  first approved it in 1997
• 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 months5
• The majority of serious adverse events with DBS
  Therapy are procedure related and temporary5

5. Activa Therapy Clinical Summary, 2009.
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.
9
What are the Risks Associated with DBS Therapy?

• There are risks to consider with DBS Therapy, as
  is the case with any brain surgery. Be sure to
  discuss the possible surgical complications and
  side effects with patients.
• Risks of brain surgery may include serious
  complications such as coma, intracranial
  hemorrhage, seizures and infection. Some of these
  risks may be fatal.
• Possible device complications include infection,
  problems with lead/extension connector
  positioning, parts wearing through the skin, or
  an interruption in therapy because of mechanical
  or electrical problems. Any of these situations
  may require additional surgery or cause symptoms
  to return.
• Some side effects associated with the stimulation
  may include worsening of tremor or speech and
  language impairments. Typically, these side
  effects are not permanent and can be resolved by
  adjusting stimulation parameters. Depression,
  suicidal thoughts, and suicide, have also been
  reported. Occurrence of fall has been observed
  in patients with Parkinsons disease.

10
Benefits of Adding MedtronicDBS Therapy
Medications Alone Medtronic DBS Therapy
0 hours of additional on time5 5.1 hours additional on time without troubling dyskinesias
Unpredictable More predictable
Dyskinesias and nonmotorside effects Medication reductions 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 maybe possible
Mean results DBS is adjunctive to medications.
5. Activa Therapy Clinical Summary, 2009.
11
When Is Medtronic DBS Therapy Appropriate?

• 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 patients goals and expectations
  to determine whether DBS
  Therapy is right
• Set realistic goals about the benefits of
  Medtronic DBS Therapy

12
Medtronic DBS Therapy in thePD Continuum of Care
Window of Opportunity
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
Upredictable on/off motor fluctuations OR
Medication-resistant tremor

• In order to obtain maximum benefit, PD patients
  must be referred at the optimal time, or during a
  window of opportunity when DBS therapy may be
  most effective.

13
Medtronic DBS Therapy Exclusion Criteria

• No longer responsive to dopaminergic medication
• Severely disabled even in the best on state
• Medical conditions that prevent surgery
• Onset of frank dementia

14
Medtronic DBS Patient Referral Advisor

• A tool that creates a patient appropriateness
  profile for DBS Therapy based on5 absolute
  criteria and 7 relative criteria
• Clinical criteria and appropriateness ratings
  were developed by an expert panel of neurologists
• Software can be downloaded at

www.medtronic.com/dbsreferraladvisor
15
Patient Management

• Establish a partnership with an implant center to
  manage postimplant patient care, which involves
• -Programming
• -Medical management

16
Device Programming

• Initial device programming Identifying and
  programming optimal stimulation parameters during
  the first several months
• Maintenance device programmingTitrating
  stimulation as needed over time
• Patient programming is reimbursed

17
Innovative Programming Software

• Medtronic has developed technology to make device
  programming easier
• Features include
• A step-by-step process that provides a systematic
  approach to programming
• The ability to capture, store and sort patient
  data in the device
• Functionality that maximizes therapeutic response
  and device longevity

18
Neuromodulation Therapies Present

• Today, more than 500,000 patients globally have
  received Medtronic neuromodulation devices.6
• DBS Therapy continues to be the fastest growing
  treatment option for people suffering from
  movement disorders.
• More than 80,000 patients globally have been
  treated with Medtronic DBS Therapy

6. Medtronic, Inc. data on file.
19
Neuromodulation Therapies Future

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

20
Medtronic Neuromodulation Therapies
PRESENT
FUTURE
Intracerebroventricular (ICV) Applications
Parkinsons Disease
Essential Tremor
Depression
Dystonia
Obsessive-Compulsive Disorder
Chronic Migraine (ONS)
Chronic Pain (Nonopioid)
Chronic Pain (Opioid)
Malignant Pain
Chronic Pain
Humanitarian Device The effectiveness of this
device for the treatment of dystonia or
obsessive-compulsive disorder has not been
demonstrated.
Spasticity
Urinary Incontinence and Retention
21
Medtronic The Leader in DBS Therapy
Medtronic is committed to advancing the science
of neuromodulation through

• Product innovation
• Education
• Procedure support
• Innovative clinical research

22
Product Innovation

• Medtronic continues to offer new products such as
• Activa PC The next generation primary cell
  neurostimulator
• Activa RC The first rechargeable
  neurostimulator for DBS Therapy
• New programming platform provides step-by-step
  guidance and advanced device programming options

23
Innovative Clinical Research

• Medtronic has sponsored numerous studies to
  evaluate the safety and efficacy of Medtronic DBS
  Therapy for current and future indications
• More than 2,000 clinical papers have been
  published on DBS Therapy

24
Approved Indications for DBS Therapy

• Parkinsons disease (FDA approved in 2002)
• Essential tremor (FDA approved in 1997)
• AAN Guidelines state that unilateral DBS resulted
  in a significant (60 to 90) reduction of
  contralateral limb tremor.7
• DBS Therapy improves activities of daily living
  in patients with ET.5
• Dystonia (FDA approved HDE in 2003)
• Obsessive-compulsive disorder (FDA approved HDE
  in 2009)
• The first psych indications approved for DBS
• Humanitarian Device The effectiveness of this
  device for the treatment of dystonia or
  obsessive-compulsive disorder has not been
  demonstrated.

5. Activa Therapy Clinical Summary, 2009. 7.
Zesiewicz TA, Elble R, Louis ED, et al. Practice
paramater therapies for essential tremor Report
of the Quality Standards Subcommittee of the AAN.
Neurology. 2005642008-2020.
25
Medtronic DBS Therapy and Your Practice

• Step 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.

26
Medtronic DBS Therapy and Your Practice
(continued)

• 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.

27
Brief Disclosures
Medtronic DBS Therapy for Parkinsons Disease,
Tremor, and Dystonia Product technical manual
must be reviewed prior to use for detailed
disclosure. Indications Medtronic DBS Therapy
for Parkinsons Disease Bilateral stimulation of
the internal globus pallidus (GPi) or the
subthalamic nucleus (STN) using Medtronic DBS
Therapy for Parkinsons Disease is indicated for
adjunctive therapy in reducing some of the
symptoms of advanced, levodopa-responsive
Parkinsons 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. Contraindica
tions 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 Parkinsons 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 tissue damage and can result in severe
injury or death. Diathermy can damage parts of
the neurostimulation 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. 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.
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. MRI
image quality may be reduced for patients who
require the neurostimulator to control tremor,
because the tremor may return when the
neurostimulator is turned off. Severe burns could
result if the neurostimulator case is ruptured or
pierced. 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 Parkinsons
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 (Parkinsons 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. Addition
ally, the abrupt cessation of stimulation for any
reason should be avoided as it may cause a return
of disease symptoms. In some cases, symptoms may
return 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 0910
28
Brief Disclosure Reclaim DBS Therapy for
OCD 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). Contraindic
ations 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
diathermys 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
Tourettes 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