Deep Brain Stimulation For Parkinson's Disease

Deep Brain Stimulation For
Parkinson’s Disease
Rajesh Pahwa, MD
Director, Parkinson’s Disease and Movement Disorder Center
Kelly E. Lyons, PhD
Director of Research and Education
Parkinson’s Disease and Movement Disorder Center
Jules M. Nazzaro, MD
Director, Stereotactic and Functional Neurosurgery
University of Kansas Medical Center

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Introduction:
Parkinson’s disease (PD) is a progressive neurodegenerative disease. Levodopa is currently
the most effective medication for the treatment of PD. When levodopa is initiated, PD symptoms
improve and are under control throughout the day. However, the long-term management of PD
with levodopa is complicated by the development of motor fluctuations and dyskinesia. Motor
fluctuations represent an inconsistent control of symptoms with times during the day when PD
symptoms are under reasonable control (on medication states) and times when PD symptoms
are bothersome (off medication states). Initially, with the addition of other PD medications or with
changes in dosing schedules, these off states can be avoided. However, as the disease
progresses, these fluctuations become unpredictable and cannot be managed by medication
adjustments. Patients may also develop involuntary dance-like or wiggling movements, known
as dyskinesia, which in some patients can be more disabling than the actual PD symptoms.
Approximately 50% of PD patients develop motor fluctuations and/or dyskinesia after five years
of treatment with levodopa. When motor fluctuations and dyskinesia cannot be managed by
medications, surgical treatments for PD are often considered. In addition, it is estimated that
tremor responds to medications in only about 50% of PD patients. Patients with medication
resistant tremor may also benefit from surgical therapy.
Surgical therapy for PD has been used since the 1950s. However, after the discovery of levodopa,
surgical therapies were abandoned due to a high rate of surgical complications and the dramatic
benefits of levodopa. The development of motor fluctuations and dyskinesia with levodopa therapy,
improvements in surgical techniques, a better understanding of the anatomy and physiology of
the brain and better brain imaging techniques like magnetic resonance imaging (MRI) led to the
reintroduction of surgical therapies for PD.

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Types of Surgeries for Parkinson’s Disease:
The current surgeries approved by the Food and Drug Administration (FDA) for the treatment of
PD include lesion surgeries and deep brain stimulation (DBS). Lesioning and DBS are typically
covered by major insurance companies.
Lesion Surgery: Lesion surgeries involve destroying a particular part of the brain to control the
symptoms of PD. Lesion surgeries for PD include:
1. Thalamotomy: a part of the ventrointermediate (VIM) nucleus of the thalamus is destroyed
primarily to reduce tremor.
2. Pallidotomy: a part of the globus pallidus interna (GPi) is destroyed to control the primary
symptoms of PD (tremor, rigidity, slowness).
3. Subthalamotomy: a part of the subthalamic nucleus (STN) is destroyed to control the primary
symptoms of PD (tremor, rigidity, slowness).
The majority of movement disorder surgical centers do not routinely perform lesion surgeries.
This is because lesion surgeries have been reported to result in more surgical complications
than DBS and by destroying parts of the brain it is possible that future treatments might not be
helpful. In addition, bilateral lesion surgeries are not recommended as they can result in severe
complications related to speech, balance and walking. Therefore, DBS is currently the surgical
procedure of choice for PD.
Deep Brain Stimulation: DBS involves implanting an electrode in the brain and connecting it
with an extension wire to an implantable pulse generator (IPG) which is pacemaker-like device
or battery most often placed in the chest. The electrode can be placed in different parts of the

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brain which include:
1. Thalamic stimulation: the electrode tip is placed in the ventrointermediate (VIM) nucleus
of the thalamus primarily to control tremor.
2. Globus pallidus interna (GPi) stimulation: the electrode tip is placed in the GPi to control
the primary symptoms of PD (tremor, rigidity, slowness) and dyskinesia.
3. Subthalamic nucleus (STN) stimulation: the electrode tip is placed in the STN to control
the primary symptoms of PD (tremor, rigidity, slowness) and dyskinesia.
One side of the brain controls the opposite side of the body, hence if the electrode is implanted
on the left side of the brain, symptoms on the right side of the body are improved. In order to
improve symptoms on both sides of the body, two DBS systems are generally implanted, one on
the right side of the brain and one on the left. These surgeries are NOT a cure for PD, they treat
the underlying symptoms of the disease.
DBS system implanted on both sides of
the brain,
Courtesy of Medtronic, Inc

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Deep Brain Stimulation (DBS)
In 1997, the FDA approved the use of the Activa Tremor Control Therapy which uses a DBS
electrode, extension wire and an implantable pulse generator (IPG) for thalamic stimulation to
control parkinsonian and essential tremor. In 2002, the FDA approved the use of the Activa
Parkinson’s Control Therapy for GPi and STN stimulation to control the primary symptoms of PD
(tremor, rigidity, slowness) and dyskinesia.
Implantable pulse generator (IPG or
neurostimulator), extension wire and electrode,
Courtesy of Medtronic, Inc
Each DBS electrode has four contacts at the tip; one, two, three or all four contacts can be turned
on depending on patient symptoms and location of the electrode.
DBS electrode
Courtesy of Medtronic, Inc

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The implantable pulse generator (IPG) is usually implanted under the skin below the collar bone.
The electrode and the IPG are connected by an extension wire. The extension wire is tunneled
from the electrode in the brain under the skin on the side of the neck to the IPG in the chest. There
are two kinds of IPGs available: 1) Soletra which controls one electrode and hence a patient who
has bilateral surgery would require two Soletra devices; 2) Kinetra allows the electrodes from
both sides of the brain to be connected to one IPG. The Kinetra IPG is approximately twice as
big as the Soletra. The IPG is programmed by a physician or nurse specialist. The patient can
turn the device on and off with an Access Review™ Therapy Controller which provides information
as to whether the devices are on or off and the battery status.
The advantages of DBS compared to lesion surgeries include no destruction of the brain so
future treatments or procedures could later be treatment options, the ability to change stimulation
parameters to increase benefit or reduce side effects and the ability to perform bilateral operations
without causing permanent speech impairment or other serious side effects. The disadvantages
of DBS include the cost of the system, the fact that an object is implanted in the brain which
increases the risk of infections, the need to periodically replace the battery (IPG) and the possibility
of mechanical problems or malfunctions of the device and its components.
Thalamic Stimulation
It was observed that during thalamotomy high frequency stimulation (greater than 100 hz) of the
target site in the brain had the same effect as destruction of the site. This led to the
development of the DBS technique. Several studies have evaluated the benefits and safety of
thalamic DBS. Approximately 90% of patients have marked reduction in tremor on the side
opposite of the surgery after thalamic DBS. Some patients show a micro-thalamotomy effect,

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a reduction of tremor after implantation of the electrode, but before the stimulator is turned on.
This is most likely due to swelling of the brain at the electrode site and this effect typically goes
away in two to four weeks after the swelling has resolved. Rarely, this effect may persist due to a
small lesion that may have occurred during placement of the electrode. Thalamic stimulation
primarily improves tremor and does not typically have any effect on slowness, rigidity, dyskinesia
or walking and balance difficulties. Long-term studies of thalamic stimulation have shown that
although tremor continues to be improved, other parkinsonian symptoms including slowness,
rigidity and gait difficulties continue to progress. Hence, thalamic stimulation is not usually rec-
ommended for PD patients unless the only disabling symptom is tremor and rigidity and slow-
ness are minimal and do not appear to be progressing.
Subthalamic Stimulation:
STN stimulation is currently the most commonly performed surgical procedure for PD. Electrodes
are usually implanted on both sides. All the major parkinsonian signs (tremor, slowness, rigidity)
improve with bilateral STN surgery. There is marked reduction in dyskinesia due to a reduction in
antiparkinsonian medications, a marked increase in on time (good symptom control) and a marked
reduction in off time (poor symptom control) after surgery. In the medication off state, the ability to
perform typically improves by 30-70% and tremor, slowness and rigidity typically improve by 40-
75%. Antiparkinsonian medications are usually reduced by 30-80% after surgery. The best
improvement that a patient can expect after surgery is usually equal to the best improvement that
they get with their antiparkinsonian medications (best medication on state); however, the patient
typically is in the on state for a longer period of time with reduced dyskinesia. Tremor is the only
symptom that may improve more with STN DBS than with medications alone. Long term results
of STN stimulation demonstrate that the improvements seen after surgery (decreased off time

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and dyskinesia) and reductions in antiparkinsonian medication dosage persist. However, due
to disease progression after 3-5 years PD symptoms may worsen but generally are still less
severe than prior to surgery. Over time patients may develop other features of advanced
disease like dementia, hallucinations and paranoia.
Pallidal Stimulation:
The results of GPi stimulation are usually similar to STN stimulation except there is typically no
reduction in antiparkinsonian medication. The improvement in PD symptoms in the medication
off state has been reported to be 25-50% and the improvement in daily functioning has ranged
from 20% to 70%. When measured by patient diaries, there is a significant reduction in dyskinesia
resulting in an increase in on time during the day. Long term results suggest that there is some
decrease in efficacy after long term follow-up. In addition, there is progression of the disease
and patients may develop symptoms such as dementia, hallucinations and paranoia. GPi
stimulation has also been shown to be effective for the treatment of dystonia.

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Candidates for surgery:
STN and GPi DBS candidates:
The criteria to identify patients for STN and GPi stimulation are similar. The team including a
neurologist, neurosurgeon and neuropsychologist determines if a patient is a candidate for surgery.
The following criteria are used to identify surgical candidates:
1. Diagnosis of idiopathic Parkinson’s disease. Patients should not have atypical PD like
multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or other
neurodegenerative conditions as atypical forms of PD have been shown to respond poorly
to the surgeries.
2. Patients should be responsive to levodopa. Patients with typical PD are responsive to
levodopa and atypical PD patients are generally not levodopa responsive. In addition,
response to levodopa prior to surgery is the best predictor of surgical outcome. The
results seen with DBS are generally comparable to the best medication on state for an
extended period of time.
3. Patients should have motor fluctuations or dyskinesia that cannot be controlled with
medications. Patients should have tried multiple classes of PD medications and should
consider surgery when disability persists. Some patients who do not have motor
fluctuations or dyskinesia but have medication resistant tremor would also be candidates
for the surgery if their tremor is disabling.
4. There should be no significant cognitive or behavioral abnormalities as these symptoms
may worsen after surgery.

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5. Patients who cannot tolerate anti-parkinsonian medications due to side effects and have
disabling PD symptoms may be candidates for surgery.
6. Patients should have the physical health and stamina to be able to undergo the surgical
procedure.
7. Patients should have realistic expectations from surgery. These procedures are not a
cure for PD and the disease will continue to progress. In addition, the best improvement
is related to an increase in on time, a reduction in dyskinesia and improvement in
medication resistant tremor.
The following criteria are usually used to exclude patients from surgery:
1. Atypical PD
2. Significant cognitive or behavioral abnormalities
3. Absence of significant disability during medication off states.
4. Lack of family support. As the surgical evaluation and stimulation programming may
require frequent sessions it would be difficult for the patient to have significant
improvement if someone was not available to assist with attending these visits.
5. Presence of uncontrolled hypertension, cardiac or other medical problems. The DBS
system is compatible with some cardiac pacemakers, this should be determined prior to
approval for surgery.
6. Presence of significant emotional problems like major depression, uncontrolled mania
or suicidal tendencies.

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