Surgical Techniques for Stereotactic
Implant of Deep Brain Stimulators
Isabelle M. Germano, M.D., FACS,1 Donald J. Weisz, Ph.D.,1 Adam Silvers, M.D.,2
R. Shrivastava, M.D.,1 and BoYi Yang, Ph.D.1
ABSTRACT
Downloaded by: NYU. Copyrighted material.
Chronic deep brain stimulation (DBS) for movement disorders is currently performed by numerous neurosurgeons. The purpose of this article is to provide the reader
with the surgical details necessary for this procedure. The selection of patients and targets
are first reviewed. The nine phases of the surgical procedure are then described, including
the use of computer-assisted technology for surgical planning and guidance. Our results
corroborate the concept that DBS is a promising surgical procedure for treatment of
movement disorders. Additional ongoing multi-center studies will allow precise determination of the role of chronic deep brain stimulation for treatment of Parkinson’s disease
and other movement disorders and the definition of the best brain target(s).
KEYWORDS: Suthalamic nucleus,globus pallidus, ventrointermediate nucleus of
the thalamus, deep brain stimulation, Parkinson’s disease, dystonia, movement
disorders
Objectives: On completion of this article the author should appreciate the current clinical and technical aspects relative to stereotactic implant of deep brain stimulators for movement disorders.
D
eep brain stimulation (DBS) was introduced
in the 1980s in Europe as a novel technique for surgical
treatment of Parkinson’s disease (PD). In this procedure, chronic high frequency stimulation is delivered to
the chosen brain target using a stereotactically implanted brain electrode connected with a pulse generator implanted in the chest, similar to a cardiac pacemaker. Controlled trial of DBS stimulation of the
ventrointermediate nucleus of the thalamus (VIM)
demonstrated the beneficial effects of this procedure for
patients with tremor secondary to PD or essential
tremor (ET).1–16 Based on this evidence, in 1997 the
FDA approved unilateral DBS of the VIM for PD and
ET. Tremor, however, is usually only one of the four car-
dinal symptoms of patients with PD. These include
rigidity, bradykinesia, and gait and postural instability.
In the past decade, a strong body of evidence from neurophysiological and experimental work supported the
concept that the subthalamic nucleus (STN) and the
globus pallidus (GPi) may be better targets to ameliorate the entire constellation of PD symptoms. Thus, in
1995 we performed the first surgery for a DBS trial focused on the study of these two alternative targets for
PD.17 Additionally, clinical evidence suggested that
DBS could be used for movement disorders other than
PD and ET, such as dystonia. Thus, we and other investigators have used DBS of the GPi for selected patients
with dystonia.
Seminars in Neurosurgery, Volume 12, Number 2, 2001. Address correspondence and reprint requests to: Isabelle M. Germano, M.D., Department
of Neurosurgery, Mount Sinai School of Medicine, One Gustave L. Levy Place, Annenberg 8–06, Box 1136, New York, NY 10029-6574.
1Department of Neurosurgery, and 2Department of Radiology (Neuroradiology), Mount Sinai School of Medicine, New York, NY. Copyright ©
2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. 1526-8012,
p;2001,12,02,213,224,ftx,en;sns00086x.
213
SEMINARS IN NEUROSURGERY/VOLUME 12, NUMBER 2 2001
This article reviews the technical details of the
surgical procedure for DBS. At our Institution, DBS
surgeries other than VIM for PD and ET are performed
with Investigation Review Board (IRB) and Food
and Drug Administration (FDA) Investigation Device
(IDE) approval.
PATIENT SELECTION
One of the most important factors for successful surgical outcome is patient selection based on accurate diagnosis. Patients who are given the diagnosis of PD may
have Parkinsonism or Parkinson’s plus syndromes.
These are also known as “multiple system atrophy”
(MSA). In either case, these syndromes respond poorly
to surgery presumably because the underlying pathophysiology is not the same as for idiopathic PD. A history of good responsiveness to levodopa upon presentation of the symptoms is a good indicator that the
diagnosis of PD is correct.
Prior to consideration for surgery, all patients
should have an adequate trial of medical therapy. Because of the fluctuating nature of the disease, “on” medication and “off ” medication neurological examinations
should be performed by an experienced neurologist
using standardized evaluation scales, such as the United
Parkinson’s Disease Rating Scale (UPDRS) and Hoehn
and Yahr scale. Most surgeons would agree that patients
with a grade 5 Hoehn and Yahr score are so disabled
that symptomatic improvement secondary to the surgery might not result in functional improvement. Thus,
they are not good surgical candidates. Dementia and
excessive brain atrophy are also considered contraindications for DBS. Contraindications for conventional
stereotactic neurosurgical procedures are also contraindications to surgery for DBS. Normal preoperative
coagulation studies are mandatory to rule out coagulopathy. Patients on chronic intake of oral anticoagulants are not considered good candidates for this procedure. Patients must stop the intake of acetylsalicilic acid
and any other medication with antiplatelet effects at
least 2 weeks prior to surgery. Uncontrolled hypertension, particularly intraoperative hypertension, is a
contraindication since it increases the risk of intraoperative hemorrhage.
Typically the patient is admitted to the hospital
the morning of the procedure. The day prior to surgery
the patient is loaded with Dilantin (1000 mg). Oral intake and medications, except for antihypertensive medications, are discontinued at midnight prior to surgery.
Anti-Parkinson’s medications are discontinued to avoid
drug-induced dyskinesias that can interfere with stereotactic frame placement and proper imaging studies for
target determination. There is also concern that dyskinesias could apply enough force on the frame to reduce
accuracy of stereotactic localization during the surgery.
Additionally, discontinuation of anti-Parkinson’s medication facilitates the immediate feedback on the effects
of the intraoperative stimulation (see below).
TARGET SELECTION
After the appropriate neurological diagnosis is confirmed and all contraindications are ruled out, a patient
with medically refractory movement disorder(s) becomes a candidate for DBS. At this point it is crucial to
decide the best brain target. The choice of target is
based on the diagnosis and symptoms. There is unanimous consensus that the VIM is the best target for ET.
For patients with advanced PD where tremor is only
one of the symptoms we prefer to use the STN. Patients
with dystonia are implanted in the GPi. Although these
are currently our target selection criteria, there have
been no studies to clearly document that these are the
best choices, as discussed below. In most cases, patients
have bilateral symptoms. Although we used to perform
simultaneous bilateral procedures, we now prefer to
stage them. Therefore, we select as the first side the
brain target opposite to the patient’s worse symptoms.
OPERATIVE PROCEDURE
The operative procedure is divided into nine stages
summarized in Table 1. The first eight phases of the
procedure are done under local anesthesia with neuroleptic analgesia. Placement of the pulse generator is
done under general anesthesia. We perform all stages in
the same day. The duration of the entire procedure is
6 to 8 hours. Postoperatively the pulse generator is
turned “on” the day of the patient’s discharge from the
hospital, that is, 48 to 72 hours after the surgery. Typically, the patients require additional visits on an outpatient basis to determine the optimal stimulation contacts and electrical parameters.
Table 1 Operative Procedure for Deep Brain
Stimulation Implant
1. Fixation of the stereotactic frame
2. Imaging for target localization
3. Preoperative planning and virtual surgery
4. Placement of recording electrode
5. Intraoperative microrecording
6. Placement of permanent electrode
7. Intraoperative macrostimulation
8. Intraoperative imaging
9. Placement of pulse generator
Downloaded by: NYU. Copyrighted material.
214
STEREOTACTIC IMPLANT OF DBS/GERMANO, ET AL
Imaging for Target Localization
The head MR localizer is then placed on the frame. The
fiducial channels of the localizer must be completely
filled with water to eliminate air bubbles that could
cause artifacts. The patient is scanned in the supine position with the frame in the head coil.
We use a Signa 1.5 Tesla scan (General Electric,
Milwaukee, WI) and special sequences for target determination (Table 2). These sequences have the advantage
of reducing spatial distortion with the T1-weighted images and excellent anatomical depiction of the GPi, the
optic tract, the internal capsule, the red nucleus, the
substantia nigra, and the STN with the T2-weighted
images. We also acquire a T1-weighted sequence to be
used for computer-assisted image-guided planning (see
below).
We obtain the first set of stereotactic coordinates
using conventional stereotactic measurement and image
Table 2 Magnetic Resonance Imaging Sequences for
Target Localization
Series
Type
Purpose
Sagittal localizer
Axial images
Coronal images
Contiguous axial
T1W
T1W
T2W
T1W
Define AC-PC plane
Obtain target coordinates
Anatomical verification of target
Computer-assisted planning
acquisition protocol. First, the AC-PC line is identified
on the sagittal localizer images. Axial 2-mm contiguous
T1- and T2-weighted images are then obtained parallel
to the AC-PC line. On T1-weighted axial images, the
slice that simultaneously depicts AC and PC is identified. The superior-inferior and lateral distance of the desired target is then calculated. The axial slice with the
appropriate superior-inferior distance to the AC-PC is
then selected and the stereotactic coordinates of the target are chosen on that slice (Fig. 1). Additionally the
“x” and “y” coordinates of the nine fiducials are calculated on the same axial slice. For targeting of the GPi
and STN, T2-weighted images are then used to visualize
anatomical landmarks, such as the external (GPe) and
internal (GPi) pallidal segments, the internal capsule,
the optic tract, the substantia nigra, and the red nucleus.
The cursor used to define the target and fiducials on the
T1-weighted images is positioned in the same location
on the T2-weighted image to assess its relationship with
the above anatomical landmarks. If necessary, adjustments based on visual anatomical landmarks are made in
the anterior-posterior, lateral, and vertical coordinates.
The last set of MR images is acquired according to our
protocol for image-guided computer-assisted guidance.
Preoperative Planning and Virtual Surgery
The MRI obtained with the computer-assisted imageguided protocol is then loaded in the StealthStation
Frame-Link software (Medtronic SNT, Louisville,
CO). This allows for display of triplanar and 3D images. Additionally, after the fiducials of the stereotactic
frame are entered in the computer together with the
AC-PC and midline points, the computer provides
real-time readout of AC-PC and CRW (or Leksell) coordinates (Fig. 2). Finally, a scalable Shaltenbrand atlas
can be overlapped to the reformatted images. This allows anatomical and neurophysiological data to display
simultaneously and it is very helpful in the refinement
of the target choice. A second set of coordinates is,
therefore, obtained with this software and compared to
the previous set. In case of discrepancy, each coordinate
(AP, lateral, vertical) can be visualized on the screen and
corrected using visual anatomical landmarks.
When the coordinates of the target are satisfactory, an entry point is selected. The entry point is chosen
Downloaded by: NYU. Copyrighted material.
Fixation of the Stereotactic Frame
We use the Cosman-Roberts-Wells (CRW) stereotactic frame. This is fixed to the patient’s head on the
morning of surgery. An intravenous infusion is secured
to the patient’s arm ipsilateral to the deep brain implant
for administration of neuroleptic analgesia. Approximately 30 minutes before placement of the frame, the
patient is sedated with Valium (5 to 10 mg) and morphine (4 to 6 mg) while (s)he is monitored on a pulse
oxymeter. With the patient in a wheelchair, the CRW
MR-compatible ring is placed over the patient’s head as
parallel as possible to the anterior-posterior commissure
(AC-PC) line. In order to parallel the AC-PC line in
the sagittal plane, the frame is positioned 15 degrees to
a line that joins the lower canthus to the ipsilateral external auditory meatus and is inclined 6 degrees from
the horizontal plane with the anterior half of the ring
being higher than the posterior half. This is roughly
achieved by having an assistant lightly supporting the
frame below the external meatus with two hands and by
allowing the frame to rest on a fingertip placed on the
patient’s nose. Correct positioning of the stereotactic
ring along the AC-PC line is much more important
when placing the Leksell frame as with this stereotactic
system the target is localized relative to the center of the
frame.
The scalp is then infiltrated to the periosteum
with local anesthetic solution of 1.0% lidocaine; approximately 2 to 4 ml is injected through each of the pinholes
using a 25-gauge needle. The stereotactic frame is then
fixed to the patient’s head using four MR-compatible
screws of the appropriate lengths. The diagonally opposed screws are advanced simultaneously and symmetrically, alternating between left and right opposing
screws. In this fashion, all screws are advanced to similar
depth to avoid rotation of the frame.
215
SEMINARS IN NEUROSURGERY/VOLUME 12, NUMBER 2 2001
A
B
C
D
Figure 1 MR images of a 70-year-old woman with ET used for target localization of the left VIM. (A) Sagittal T1-weighted localizer
image depicting the AC and PC. (B) Sagittal image showing the position of the axial slices shown below and acquired parallel to the
AC-PC line. (C) Axial image used to determine the location of the target. First, the length of the intercommisural line (IC, labeled 1,
26 mm). The crossing of the lines indicates the AP target calculated using conventional coordinates.17a From this point the lateral coordinate is calculated at 14 mm from the midline (labeled 2). (D) The vertical coordinate is 3 mm above the AC-PC plane.
anterior to the coronal suture and approximately 3 cm lateral to midline. Great care is taken to ensure that the entry
point is on a gyrus and not on a sulcus to avoid cortical
hemorrhages. After the entry point is chosen, the computer displays the planned trajectory and the anteriorposterior and lateral arc coordinates for the frame. At this
point additional computer-reformatted images can be
displayed to allow performance of virtual surgery (Fig. 2).
In particular the “probe eye’s view” reformatted image allows us to follow the planned path of the electrode
through the brain. It is very important to assure that the
planned path does not interfere with the sulci, the ventricular system, and the internal capsule. If the planned
trajectory is not satisfactory, the entry point is changed
and new trajectories can be displayed until the optimal
one is found. Additionally, performance of virtual surgery
with three-dimensional and triplanar images is an excellent teaching tool for residents in training.
Placement of the Recording Electrode
Although preoperative imaging studies are required to
allow localization of the target, proper target localization is confirmed by intraoperative microrecording and
macrostimulation. In the operating room, the patient
lies supine on the operating room table with the frame
fixed to the Mayfield head clamp adapter. The patient
receives intravenous antibiotics (cefuroxime 1 gr) and
steroids (dexamethasone 10 mg). The blood-pressure
cuff and the oxygen saturation monitor are placed on
the arm ipsilateral to the side of the deep brain stimulator implant to allow free neurological testing of the contralateral limbs during surgery.
The patient’s hair is shaved anterior to the coronal suture. The entry point is marked using the frameless equipment. Lidocane 1% 1:200,000 with epinephrine is injected at the entry point. The patient’s head
is draped with a transparent drape (Apuzzo drape,
Downloaded by: NYU. Copyrighted material.
216
Figure 2 Preoperative planning and virtual surgery. Intraoperative photograph of the computer screen displaying axial and reformatted coronal, sagittal, and 3D images while planning the target, entry point, and trajectory for a left STN DBS. (A) After the fiducials, AC, PC, and midline points are entered in the computer, a reformatted patient’s scaled Schaltenbrand atlas is overlapped to the
triplanar images. By clicking on the reformatted images (the dot on the images represents the chosen STN) the computer allows for
real-time reading of the CRW coordinates in the dialog box (right-hand side). (B). After the target is selected, the entry point is chosen (see text) and the trajectory displayed as a line on the triplanar images. Virtual surgery can be performed by scrolling the bar in
the dialog box and visualizing the planned path on computer reformatted images (right lower quadrant). This allows to optimization
of the trajectory if necessary (see text).
Radionics, Burlington, MA). This allows the patient’s
face to be seen during the stimulation. Sedatives are administered intravenously by the anesthesiologist as
needed. These are short lasting and are meant to sedate
the patient during the placement of the burr hole only.
The patient’s full cooperation during the remainder of
the surgery is desirable. Blood pressure should be kept
under strict control at all times, using intravenous antihypertensive medications if necessary.
The CRW stereotactic arc is adjusted with the
stereotactic coordinates obtained as described above.
This is then mounted on a rigid CRW phantom to validate the accuracy of the hardware and then is assembled
into the patient’s frame. A stereotactic guided linear
skin incision, approximately 4 cm long, is made centered on the entry point and parallel to midline. A
14-mm burr hole is then made with a craniotome using
a disposable burr (Acrucat, Codman, Philadelphia, PA).
A burr hole ring is placed around the hole to allow fixation of the permanent electrode at the end of the procedure. The dura is cauterized with the bipolar and kept
closed. A guiding cannula is then mounted on the
CRW arc held by a digital microdrive (Radionics,
Burlington, MA). A brain cannula is then inserted
trough the dura bluntly and advanced to 20 mm above
the target. A large piece of gelfoam is packed around the
cannula on the dura to prevent CSF leak during the recording.
Intraoperative Microrecording
We utilize monopolar tungsten electrodes with a tip diameter of 0.25 micron and impedance of 500k ohms at
1k Hz (FHC, Brunswick, ME). After the cannula stylet
217
Downloaded by: NYU. Copyrighted material.
STEREOTACTIC IMPLANT OF DBS/GERMANO, ET AL
SEMINARS IN NEUROSURGERY/VOLUME 12, NUMBER 2 2001
is removed, the microelectrode is inserted through the
brain cannula. The tip of the microelectrode is then advanced though the brain cannula. This extends 10 mm
beyond the brain cannula. At this point the microelectrode impedance is verified. Electrodes are replaced if
the impedance is less than 200k ohms or greater than
500k ohms.
The microelectrode is further advanced in micrometer increments, using a digital microdrive. After
waiting for 2 to 3 minutes for the brain to stabilize in
position relative to the recording electrode, the tip is
slowly advanced until extra cellular spikes are seen and
heard from the recordings.
The microelectrode recordings are amplified (gain
= 5000) and bandpass filtered (300 to 10,000 Hz). The
output of the amplifier is sent to a storage oscilloscope, an
audioamplifier, a window discriminator, an analogto-digital converter connected to a personal computer,
and a digital tape drive (for archival storage). Additional
details of the microrecording equipment are reported
elsewhere.18 Identification of the target structure through
microelectrode recordings is accomplished by analyzing
the characteristics of the neuronal recordings. As the microelectrode enters the STN, there is a sudden increase in
the number of spikes being recorded because cells in the
STN are much more densely packed and tonically active
than are cells immediately above the structure. Single
cells are isolated in order to obtain additional information
about the neuronal firing patterns and rates. It is our experience that these cells can be more difficult to isolate
than are cells in surrounding areas because of the STN’s
higher cell density. As an aid in isolating single cells from
a recording that contains two or more cells we also use
template-matching spike sorting software.
In our recordings most STN cells have shown an
irregular firing pattern with periods of bursts and pauses
(Fig. 3A). We have also observed tremor-related patterns of activity in patients who were exhibiting tremor
at the time of the recordings. The cell density (high),
pattern of activity (bursts of spikes and irregular firing
patterns or tremor-related activity), firing rate (10 to
80 spikes/sec), and spike morphology (0.5 to 0.8 msec
width) are our main criteria for STN localization.
When placing a DBS in the GPi, typically the
microrecording starts in the GPe. Cells in the GPe normally exhibit one or two patterns of firing, neither of
which is regular. One pattern consists of rapid bursts
lasting greater than 500 msec that are separated by very
low rates of discharge or silence that can last for more
than 0.5 msec. The second pattern consists of very slow
firing interspersed with occasional short bursts of
spikes. As the electrode moves to the GPi there is a
brief silence and reduced background activity, indicating
that the tip is probably in the internal medullary lamina.
Unlike the GPe, the GPi cells exhibit continuous
discharge without periods of silence. Firing rates of
the GPI cells range from 10 spikes/sec to over
100 spikes/sec (Fig. 3B). As the electrode reaches the
ventral part of the GPi, the background activity decreases. This indicates the presence of white matter,
possibly the optic tract. At this point microstimulation
(less than 20 mA) of the electrode is performed to
evoke visual sensation. If electrical stimulation fails to
elicit visual sensation, we record visual evoked responses from the same electrode. Recordings are made
in correspondence to a flashing light that is computer
controlled. Generally 20 to 50 stimuli are averaged and
analyzed.
Typical microelectrode recording of the VIM reveals noisy, high-voltage spontaneous activity (Fig. 3C),
albeit less than that observed in the ventrocaudal (VC)
thalamus. Additionally, in the VIM, kinesthetic neurons
respond to deep (not superficial) movements of the
joints. There is a topographic orientation, with the lower
limb dorsolateral, upper limb ventromedial, and face
most medial. Finally, single-cell recording of the VIM
shows cells that discharge at tremor frequency and cease
firing when the tremor is arrested. These are also known
as “tremor cells.” Responses of single unit discharges to
passive movements of the contralateral or ipsilateral
limbs are also detected intraoperatively by analyzing the
corresponding changes in neuronal firing rates and patterns as visualized on the oscilloscope, heard on the audiomonitor, and analyzed by computer software.
Placement of the Permanent Electrode
After adequate localization of the target is performed by
microelectrode recording, the microelectrode and cannula are withdrawn. A larger cannula is then placed up
to 10 mm above the target and the permanent electrode
is passed into the cannula to reach the target. The permanent electrode is a 1.2 mm-diameter, tetrapolar electrode with four contacts, each 1.5 mm long at 1.5-mm
distance from each other [Model 3387, Medtronic,
Minneapolis, MN]. The most distant contact, known as
contact “0,” is placed at “target.” The target for the permanent electrode is defined intraoperatively by the
stereotactic coordinates of the track where the neurophysiological characteristics of the specific target were
seen with the largest millimetric range.
Intraoperative Macrostimulation
The permanent electrode is then connected to a test
stimulator. Macrostimulation is performed at high frequency greater than 100 Hz, to check for benefit, and
low frequency less than 100 Hz, to rule out side effects.
Typically, resolution of the tremor and improvement of
rigidity are seen at high frequency. Motor effects, including tetanic contractions, seen at low voltage, suggest
proximity to the internal capsule. When targeting the
Downloaded by: NYU. Copyrighted material.
218
STEREOTACTIC IMPLANT OF DBS/GERMANO, ET AL
219
Downloaded by: NYU. Copyrighted material.
A
B
C
Figure 3 Oscilloscope tracings of intraoperative microelectrode recordings. Five seconds of activity are shown in each tracing
(x-axis). Representative samples of the firing pattern, as described in the text, of a cell in (A) the STN; (B) the GPi; and (C) the VIM.
STN, oculomotor effects, including mydriasis, indicate
too-far medial location of the electrode. In the thalamus, speech disturbances, such as anomia, indicate
proximity to the anterior nuclei, speech arrest to the
medial nuclei, sensory disturbances, including paresthesias, to the posterolateral nuclei. Upon completion of
the macrostimulation, the stylet is then removed from
the electrode and the cannula is withdrawn from the
brain. The electrode is secured to the burr hole ring with
the burr hole cap. The skin is closed with nylon.
Intraoperative Imaging
The patient is then brought to the MR scanner to confirm correct positioning of the electrode and rule out
presence of intracerebral hemorrhage (Fig. 4). This
could be a contraindication to proceeding with the last
phase of the surgery, that is, placement of the pulse gen-
erator. After the MR images are acquired, the stereotactic frame is removed and the patient returned to the operating room.
Placement of the Pulse Generator
This stage of the surgical procedure is most readily accomplished under general anesthesia. The patient is positioned prone on the operating room table with the
head in a donut holder rotated to the side opposite the
implant. The head, neck, and superior half of the chest
are prepped and draped. A linear skin incision is made
below and parallel to the clavicle after infiltration with
lidocaine 1:200,000 with epinephrine. A subcutaneous
pocket over the muscle fascia is then dissected similar to
that used for a cardiac pacemaker. The pocket should be
big enough to accommodate the entire pulse generator
and to avoid having the skin incision positioned over it.
SEMINARS IN NEUROSURGERY/VOLUME 12, NUMBER 2 2001
Figure 4 Postoperative axial MR image of the same
patient shown in Figure 1, confirming the location of
the deep brain electrode in the left VIM. The electrode
contact is seen in the left VIM as a signal void. Postoperatively, the patient had complete control of her essential tremor in the right upper extremity.
The incision over the head is then reopened and the distal part of the electrode externalized. A tunneling device
is then used to pass the connecting wire under the skin.
This is then connected to the electrode proximally and
to the pulse generator distally. The connecting wire is inserted in the distal part of the electrode and held in place
by four screws. These are tightened with a hex wrench to
achieve a finger-tight fit. The connection is then covered
with a silicon boot. It is important that the connection
not be placed over the parietal boss to avoid skin erosion.
We place it toward the convexity; alternatively it could
be placed behind the ear. The distal part of the connecting wire has two pins. These are inserted in the pulse
generator and fixed by four screws closed with the hex
wrench to achieve a finger-tight fit. Excess cable is carefully positioned behind the pulse generator. The pulse
generator is then placed in the subcutaneous pocket with
great care to position the engraved part of the stimulator
toward the skin. If this is positioned toward the chest
wall, percutaneous telemetry may be difficult to accomplish. The incisions are then closed in anatomical layers
and dressed in the usual sterile fashion.
RESULTS
We participated in a multicenter trial that evaluated
96 patients and 38 patients who underwent bilateral
STN and GPi DBS, respectively. These were followed
for 6 months, with a double-blind, cross-over assess-
ment at 3 months. Significant benefits of stimulation
were observed with stimulation in both “off ” and “on”
states. Stimulation for the “off ” state provided significant improvement of all the cardinal features of PD.
Benefits were confirmed in the double-blind, cross-over
study and approximated to those obtained with L-dopa,
but with a decrease in motor fluctuations, increased “on”
time without dyskinesia, and reduced “off ” period severity. The L-dopa dose was reduced by approximately
30% in these patients. In this trial, patients were not
randomized to STN or GPi, so the study was not directed to compare these two targets. The detailed results
of our patients, including improvement of UPDRS
scores, have been published elsewhere.18a
DISCUSSION
Intraoperative stimulation at high frequency (greater
than 100 Hz) of the motor thalamus has long been performed during ablative surgery for movement disorders
to provide electrophysiological confirmation of the target location prior to lesioning.19–22 Chronic stimulation
of the motor thalamus is very effective for medically refractory ET and PD tremor. In a series of 80 PD, Benabid found that 88% had complete or near complete resolution at the longest follow-up ranging from 6 months
to 8 years.4 Similar efficacy has been noted in open trials.11,12 Bilateral thalamic DBS has been reported to be
more effective than unilateral DBS in controlling bilat-
Downloaded by: NYU. Copyrighted material.
220
STEREOTACTIC IMPLANT OF DBS/GERMANO, ET AL
animal and human studies suggests that neurotransmitter and fiber activation also may be an important mechanism for DBS. Long-term effects of DBS in the brain
are not known.
DBS offers several theoretical advantages when
compared to ablative procedures. First, the stimulation
parameters can be adjusted at any time in an attempt to
maximize efficacy and minimize adverse events. Second, since a destructive lesion is not performed, DBS
does not preclude the opportunity to employ neuroprotective or restorative therapies when and if they become
available.
On the other hand, DBS has some disadvantages. First, the use of a mechanical device implies that
malfunction or infection of the equipment could occur
at any given time throughout the patient’s life. Second,
since the lifespan of the pulse generator battery is restricted (2 to 5 years) additional surgery is necessary to
replace it. Third, the DBS system is costly. Finally, the
stimulator adjustments require frequent and prolonged
out-patient visits to optimize the stimulation.
CONCLUSIONS
As is true of ablative procedures, high-frequency
chronic DBS is a technically challenging procedure that
requires stereotactic skills and excellent knowledge of
the anatomy and physiology of the basal ganglia.
Although DBS may have theoretical advantages over
ablative procedures, further clinical experience with longterm follow up is necessary to establish if these advantages are real. Thus, at the present time the decision to
treat a PD patient with an ablative procedure or DBS
rests solely on the patient-physician’s decision. Additional multicenter studies are necessary to allow precise
determination of the role of chronic DBS for treatment
of PD and other movement disorders and to define the
best brain target(s).
REFERENCES
1. Alesch F, Pinter MM, Helscher RJ, et al. Stimulation of the
ventral intermediate thalamic nucleus in tremor dominated
Parkinson’s disease and essential tremor. Acta Neurochir 1995;
136:75–81
2. Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J.
Combined (thalamotomy and stimulation) stereotactic surgery
of the VIM thalamic nucleus for bilateral Parkinson disease.
Appl Neurophysiol 1987;50:334–346
3. Benabid A, Pollak P, Cervason C, et al. Long-term suppression
of tremor by chronic stimulation of the ventral intermediate
thalamic nucleus. Lancet 1991;337:403–406
4. Benabid AL, Pollak P, Gao D, et al. Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as
a treatment of movement disorders. J Neurosurg 1996;84:
203–214
Downloaded by: NYU. Copyrighted material.
eral appendicular and midline tremor.23 In a randomized trial, DBS resulted in similar high level of tremor
relief with significantly fewer complications than VIM
thalamotomy.24 Relief of rigidity, bradykinesia, and gait
and postural instability is, however, reportedly unaffected by VIM stimulation. Thus, alternative targets are
investigated, namely the STN and GPi.
An increasing number of reports describe the effects of chronic unilateral or bilateral pallidal stimulation for PD.25–33 Improvements in UPDRS motor
scores during stimulation were highly variable, ranging
from statistically insignificant25 to significant changes
of 11 to 70% in other reports.26–31 Similarly to pallidotomy, pallidal stimulation improves contralateral tremor,
rigidity, bradykinesia, and L-dopa–induced dyskinesias.
Improvement in axial symptoms and gait and postural
stability has been reported; however, this is not a unanimous finding.25–33 Multiple factors can contribute to
the variability of improvements after GPi DBS. These
factors include surgical technique, small sample size,
and location of the permanent electrode. Efforts to proceed with larger prospective and controlled studies are
in progress.
Benabid and colleagues34–36 pioneered bilateral
STN DBS in PD patients. In their experience, UPDRS
motor scores and activity of daily living (ADL) scores
improved by 42 to 82% 3 months after the surgery. All
PD symptoms improved in the “off ”state with akinesia
and rigidity improving the most. More than with any
other procedure, the “on” state symptoms that are
L-dopa–resistant are improved.35 Additionally, after
STN DBS, patients were able to significantly decrease
their L-dopa intake. Thus, drug-induced dyskinesias
are improved after STN DBS. Numerous other clinical
reports confirmed these findings.34–44
The exact mechanisms by which chronic electrical stimulation is efficacious are complex and still poorly
understood. It is well known that the effects of stimulation are only seen while the stimulation occurs and they
stop within seconds of stopping the stimulation. It
seems clear that DBS simulates the effects of a lesion
without the need to make a brain lesion. At typical
stimulation parameters, tissue within 2 to 3 mm of the
stimulating electrode is likely to be affected, but could
vary greatly depending on the stimulation parameters.
Stimulation could directly activate cells or axons by depolarization, but could also inactivate cells or axons by
depolarization blockade. Furthermore, electrical stimulation can activate adjacent long tract white matter
fibers either orthodromically or antidromically. Activation of cells or fibers could have similar behavioral effects as inactivation by increasing release of inhibitory
neurotransmitters, overriding abnormally patterned activity, with a constant frequency signal, or by numerous
other hypothetical mechanisms.35 Although there is evidence for local neuronal blockade, other evidence from
221
SEMINARS IN NEUROSURGERY/VOLUME 12, NUMBER 2 2001
5. Blond S, Siegfried J. Thalamic stimulation for the treatment
of tremor and other movement disorders. Acta Neurochir
Suppl 1991;52:109–111
6. Blond S, Caparros-Lefebvre D, Parker F, et al. Control of
tremor and involuntary movement disorders by chronic
stereotactic stimulation of the ventral intermediate thalamic
nucleus. J Neurosurg 1992;77:62–68
7. Burleigh AL, Horak FB, Burchiel KJ, et al. Effects of thalamic stimulation on tremor, balance, and step initiation: a
single subject study. Mov Disord 1993;8:519–524
8. Caparros-Lefebvre D, Ruchoux MM, Blond S, Petit H,
Percheron G. Long-term thalamic stimulation in Parkinson’s
disease: postmortem anatomoclinical study. Neurology 1994;
44:1856–1860
9. Deiber MP, Pollak P, Passinghan R, et al. Thalamic stimulation and suppression of parkinsonian tremor: evidence of a
cerebellar deactivation using positron emission tomography.
Brain 1993;116:267–279
10. Hassler R. The influence of stimulations and coagulations in
the human thalamus on the tremor at rest and its physiopathologic mechanism. Excerpta Media Foundation 1955;
2:637–642
11. Hubble JP, Busenbar KL, Wilkinson S, et al. Effects of thalamic deep brain stimulation based on tremor type of diagnosis. Mov Disord 1997;12(3):337–341
12. Koller W, Pahwa R, Busenbark K, et al. High-frequency unilateral thalamic stimulation in the treatment of essential and
parkinsonian tremor. Ann Neurol 1997;42:292–299
13. Ondo W, Jankovic J, Schwartz K, Almaguer M, Simpson RK.
Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson’s disease tremor. Neurology
1998;51:1063–1069
14. Siegfried J and Lippitz B. Bilateral chronic electrostimulation
of ventroposterolateral pallidum: a new therapeutic approach
for alleviating all Parkinsonian symptoms. Neurosurgery
1994;35:1126–1130
15. Tasker RR. Deep brain stimulation is preferable to thalamotomy for tremor suppression. Surg Neurol 1998;49:145–153
16. Andy DJ. Thalamic stimulation for control of movement disorders. Appl Neurophysiol 1983;46:107–111
17. Olanow CW, Germano IM, Brin MF, Swope D, Weisz D.
Deep brain stimulation of the subthalamic nucleus for
Parkinson’s disease. Mov Disord 1996;11(5):598–599
17a.Kelly PJ. Therapy of Parkinson’s Disease. New York: Marcel
Dekker; 1990
18. Weisz D and Yang B. Intraoperative electrophysiological recording techniques. In: Germano IM, ed. Neurosurgical
Treatment of Movement Disorders. Park Ridge, IL: AANS
Publication Committee, 1998:207–218
18a.Olanow CW, Brin MF, Obeso JA. The role of deep brain
stimulation as a surgical treatment of Parkinson’s disease.
Neurology 200;55(S60-S66)
19. Hassler R, Riechert T, Munginger F, Umbach W, Ganglberger JA. Physiological observations in stereotaxic operations in extrapyramidal motor disturbances. Brain 1960;83:
337–350
20. Bertrand G, Jasper H, Wong A, Mathews G. Microelectrode
recording using stereotactic surgery. Clin Neurosurg 1966;
16:328–356
21. Hirai T, Miyazaki M, Nakajima H, Shibazaki T, Ohye C. The
correlation between tremor characteristics and the predicted
volume of effective lesions in stereotaxic nucleus ventralis intermedius thalamotomy. Brain 1983;106:1001–1018
22. Tasker RR, Organ LW, Hawrylyshyn P. Investigation of the
surgical target for alleviation of involuntary movement disorders. Appl Neurophysiol 1982;45:261–274
23. Ondo W, Almaguer M, Jankovic J, Simpson R. Thalamic
deep brain stimulation: comparison between unilateral and
bilateral placement. Arch Neurol 2001;58:218–222
24. Schuurman PR, Bosch DA, Bossuty PMM, et al. A comparison of continuous thalamic stimulation and thalamotomy for
suppression of severe tremor. N Engl J Med 2000;342:
461–468
25. Tronnier VM, Fogel W, Kronenbuerger M, Steinvorth S. Pallidal stimulation: an alternative to pallidotomy? J Neurosurg
1997;87:700–705
26. Burchiel KJ, Anderson VC, Favre J, Hammerstad JP. Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson’s disease: results of a randomized, blinded pilot study. Neurosurgery 1999;45:1375–
1384
27. Durif F, Lemaire JJ, Debilly B, Dordain G. Acute and chronic
effects of anteromedial globus pallidus stimulation in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1999;67: 315–
322
28. Gálvez-Jiménez N, Lozano A, Tasker R, Duff J, Hutchison
W, Lange AE. Pallidal stimulation in Parkinson’s disease patients with a prior unilateral pallidotomy. Can J Neurol Sci
1998;25:300–305
29. Ghika J, Villemure JG, Fankhauser H, et al. Efficiency and
safety of bilateral contemporaneous pallidal stimulation (deep
brain stimulation) in levodopa-responsive patients with
Parkinson’s disease with severe motor fluctuations: a 2-year
follow-up review. J Neurosurg 1998;89:713–718
30. Gross C, Rougier A, Guehl D, Boraud T, Julien J, Bioulac B.
High-frequency stimulation of the globus pallidus internalis
in Parkinson’s disease: a study of seven cases. J Neurosurg
1997;87:491–498
31. Troster AI, Fields JA, Wilkinson SB, et al. Unilateral pallidal
stimulation for Parkinson’s disease: neurobehavioral functioning before and 3 months after electrode implantation. Neurology 1999;49:1078–1083
32. Vingerhoets G, van der Linden C, Lanno E, et al. Cognitive
outcome after unilateral pallidal stimulation in Parkinson’s
disease. J Neurol Neurosurg Psychiatry 1999;66:297–304
33. Hristova A, Lyons K, Troster A, Pahwa R, Wilkinson S,
Koller W. Effect and time course of deep brain stimulation of
the globus pallidus and subthalamus on motor features
of Parkinson’s disease. Clin Neuropharmacol 2000;23(4):
208–211
34. Limousin P, Pollak P, Hoffman D, Benazzouz A, Perret JE,
Benabid AL. Abnormal involuntary movements induced by
subthalamic nucleus stimulation in parkinsonian patients.
Mov Disord 1996;11:231–235
35. Limousin P, Krack P, Pollak P, et al. Electrical stimulation of
the subthalamic nucleus in advanced Parkinson’s disease.
N Engl J Med 1998;339:1105–1111
36. Limousin PL, Pollak P, Benazzouz A, et al. Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus
stimulation. Lancet 1995;345:91–95
37. Krack P, Pollack P, Limousin P, et al. Subthalamic nucleus or
internal pallidal stimulation in young onset Parkinson’s disease. Brain 1998;121:451–457
38. Krack P, Benazzouz A, Pollak P, et al. Treatment of tremor in
Parkinson’s disease by subthalamic nucleus stimulation. Mov
Disord 1998;13:907–914
Downloaded by: NYU. Copyrighted material.
222
STEREOTACTIC IMPLANT OF DBS/GERMANO, ET AL
43. Pinter MM, Alesch F, Murg M, Seiwald M, Helscher RJ,
Binder H. Deep brain stimulation of the subthalamic nucleus
for control of extrapyramidal features in advanced idiopathic
Parkinson’s disease: one-year follow-up. J Neural Transm
1999;106:693–709
44. Rodriguez-Oroz MC, Gorospe A, Guridi J, et al. Bilateral
deep brain stimulation of the subthalamic nucleus in Parkinson’s disease. Neurology 2000;55(Suppl 6):S45–S51
Downloaded by: NYU. Copyrighted material.
39. Kumar R, Lozano AM, Kim YJ, et al. Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson’s disease. Neurology 1998;51:850–855
40. Molinuevo J, Valldeoriola F, Tolosa E, et al. Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson’s disease. Arch Neurol 2000;57:983–988
41. Moro E, Scerrati M, Romito LM, Roselli R, Tonali P, Albanese A. Chronic subthalamic nucleus stimulation reduces
medication requirements in Parkinson’s disease. Neurology
1999;53:85–90
42. Pillon B, Ardouin C, Damier P, et al. Neuropsychological
changes between “off ” and “on” STN or GPi stimulation in
Parkinson’s disease. Neurology 2000;55:411–418
223
Downloaded by: NYU. Copyrighted material.