Single electrode and multiple electrode guided electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease.

Abstract

It is still debated to what extent intraoperative electrophysiological techniques contribute to the outcome of subthalamic nucleus (STN) deep brain stimulation (DBS). Intraoperative electrophysiological recordings for identification of the STN can be made with one electrode or with multiple, simultaneously implanted electrodes. The latter provide more detailed information about the electrophysiological boundaries of the STN; however, implantation of several electrodes at one time might increase the risk of bleeding. Here we report the results of a study of patients with advanced Parkinson's disease, in which one group of patients underwent bilateral STN DBS with electrophysiological recordings from a single electrode, and the other group received STN DBS with multiple (five or fewer) simultaneously implanted electrodes.
Fifty-five patients suffering from advanced Parkinson's disease who underwent bilateral STN stimulation were included in this study. Thirty-two patients underwent STN DBS guided by a single semi-microelectrode, and 23 patients underwent STN DBS guided with simultaneously implanted multiple microelectrodes. All patients were examined preoperatively and 3 and 12 months postoperatively with regard to activities of daily living, motor functions, and neuropsychological functions.
We found that the simultaneous implantation of multiple electrodes does not increase the risk of bleeding or any other major intracranial complication. The use of multiple electrodes resulted in better motor results when compared with patients who underwent STN DBS guided with a single recording electrode. There were significantly more improvements in patients' tremor and rigidity, and as a consequence, a better total Unified Parkinson Disease Rating Scale, Part III score was identified during the medication-off phase. Despite better motor effects, patients treated with multiple electrodes showed subtle deterioration in neuropsychological functions, particularly in memory function.
STN DBS performed with multiple electrophysiological recording electrodes resulted in better motor outcome but induced specific mild declines in neuropsychological functions.

Full text

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ONS346 | VOLUME 61 | OPERATIVE NEUROSURGERY 2 | NOVEMBER 2007
www.neurosurgery-online.com
FUNCTIONAL AND STEREOTACTIC
Clinical Studies
SINGLE ELECTRODE AND MULTIPLE ELECTRODE
GUIDED ELECTRICAL STIMULATION
OF THE SUBTHALAMIC NUCLEUS IN ADVANCED
PARKINSON’S DISEASE
OBJECTIVE: It is still debated to what extent intraoperative electrophysiological tech-
niques contribute to the outcome of subthalamic nucleus (STN) deep brain stimulation
(DBS). Intraoperative electrophysiological recordings for identification of the STN can
be made with one electrode or with multiple, simultaneously implanted electrodes.
The latter provide more detailed information about the electrophysiological bound-
aries of the STN; however, implantation of several electrodes at one time might increase
the risk of bleeding. Here we report the results of a study of patients with advanced
Parkinson’s disease, in which one group of patients underwent bilateral STN DBS with
electrophysiological recordings from a single electrode, and the other group received
STN DBS with multiple (five or fewer) simultaneously implanted electrodes.
PATIENTS AND METHODS: Fifty-five patients suffering from advanced Parkinson’s dis-
ease who underwent bilateral STN stimulation were included in this study. Thirty-two
patients underwent STN DBS guided by a single semi-microelectrode, and 23 patients
underwent STN DBS guided with simultaneously implanted multiple microelectrodes.
All patients were examined preoperatively and 3 and 12 months postoperatively with
regard to activities of daily living, motor functions, and neuropsychological functions.
RESULTS:We found that the simultaneous implantation of multiple electrodes does not
increase the risk of bleeding or any other major intracranial complication. The use of
multiple electrodes resulted in better motor results when compared with patients who
underwent STN DBS guided with a single recording electrode. There were significantly
more improvements in patients’ tremor and rigidity, and as a consequence, a better
total Unified Parkinson Disease Rating Scale, Part III score was identified during the
medication-off phase. Despite better motor effects, patients treated with multiple elec-
trodes showed subtle deterioration in neuropsychological functions, particularly in
memory function.
CONCLUSION: STN DBS performed with multiple electrophysiological recording elec-
trodes resulted in better motor outcome but induced specific mild declines in neu-
ropsychological functions.
KEY WORDS: Deep brain stimulation, Microelectrode recording, Parkinson’s disease, Subthalamic nucleus
Neurosurgery 61[ONS Suppl 2]:ONS346–ONS357, 2007
B
ment of patients suffering from advanced
Parkinson’s disease (PD). Many studies have
appeared describing the short- and long-term
effects of bilateral STN DBS for patients with
PD (2, 4, 8–11, 13–15, 21). These studies consis-
DOI: 10.1227/01.NEU.0000280137.83797.6F
Yasin Temel, M.D., Ph.D.
Department of Neurosurgery,
University Hospital Maastricht, and
European Graduate School
of Neuroscience,
Maastricht, The Netherlands
Poldi Wilbrink, M.D.
Department of Neurosurgery,
University Hospital Maastricht, and
European Graduate School
of Neuroscience,
Maastricht, The Netherlands
Annelien Duits, Ph.D.
Department of Medical Psychology,
University Hospital Maastricht,
Maastricht, The Netherlands
Peter Boon, M.Sc.†
Department of Medical Psychology,
University Hospital Maastricht,
Maastricht, The Netherlands
Selma Tromp, M.D., Ph.D.
Departments of Neurology and
Clinical Neurophysiology,
University Hospital Maastricht,
Maastricht, The Netherlands
Linda Ackermans, M.D.
Department of Neurosurgery,
University Hospital Maastricht, and
European Graduate School
of Neuroscience,
Maastricht, The Netherlands
Vivianne van Kranen-
Mastenbroek, M.D., Ph.D.
Department of Clinical
Neurophysiology,
University Hospital Maastricht,
Maastricht, The Netherlands
Wim Weber, M.D., Ph.D.
Department of Neurology,
University Hospital Maastricht,
Maastricht, The Netherlands
Veerle Visser-Vandewalle,
M.D., Ph.D.
Department of Neurosurgery,
University Hospital Maastricht, and
European Graduate School
of Neuroscience,
Maastricht, The Netherlands
†Deceased
Reprint requests:
Yasin Temel, M.D., Ph.D.,
Department of Neurosurgery,
University Hospital Maastricht,
P.O. Box 5800,
6202 AZ Maastricht, The Netherlands.
E-mail: y.temel@np.unimaas.nl
Received, November 8, 2006.
Accepted, April 12, 2007.
ilateral deep brain stimulation (DBS) of
the subthalamic nucleus (STN) is
presently widely performed for the treat-
tently show that patients with PD significantly
benefit from this procedure. However, the
results vary between centers (7). It is likely that
these differences in outcome are at least partly
related to differences in surgical procedure.
Even at present there is no standard procedure,
and the imaging technique for localization of
the target and the use of intraoperative electro-

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NEUROSURGERY
VOLUME 61 | OPERATIVE NEUROSURGERY 2 | NOVEMBER 2007 | ONS347
GUIDED ELECTRICAL STIMULATION IN PARKINSON’S DISEASE
physiological recordings and test stimulations often depend
on the surgeon’s preferences and experience.
It has been suggested that electrophysiological identifica-
tion of the STN is an important tool in the correct placement
of stimulating electrodes (3). Presently, it is still debated to
what extent intraoperative electrophysiological techniques
contribute to the outcome of STN DBS. A recent study
showed that patients who underwent implantation of STN
electrodes with intraoperative electrophysiological record-
ings had significantly better results with regard to Parkinson-
ian motor disability than patients who underwent the same
surgery without these techniques (5). Intraoperative electro-
physiological recordings for identification of the STN can be
made with one electrode or with multiple simultaneously
implanted electrodes. The latter provide more detailed infor-
mation about the electrophysiological boundaries of the STN,
but implantation of several electrodes at one time might
increase the risk of bleeding. The key question is whether
this supposed increase in risks is counterbalanced by a better
clinical outcome. Here we report the results of a study of
patients with advanced PD, in which one group of patients
underwent bilateral STN DBS with electrophysiological
recordings from a single electrode, and the other group
received STN DBS with multiple (five or fewer), simultane-
ously implanted electrodes.
PATIENTS AND METHODS
Patients
Between November of 1999 and June of 2005, patients were selected
for STN stimulation if they had clinical findings consistent with idio-
pathic PD and, despite optimal pharmacological treatment, severe
response fluctuations and/or dyskinesias. Good initial L-dopa response
was an absolute criterion. The one exception to this was the inclusion
of patients who demonstrated L-dopa-resistant rest tremor. Exclusion
criteria consisted of significant atrophy, multiple white-matter lesions,
or other focal brain abnormalities on magnetic resonance imaging,
Hoehn and Yahr Stage 5 at the best moment of the day, a score of less
than 24 on the Mini-Mental State Examination, psychosis, and general
contraindications for surgery such as severe hypertension or blood
coagulation disorders. Informed consent was obtained from all
patients, and STN DBS was approved by the local ethics committee.
In the first group of consecutive patients (Group A), surgery was
performed using a single recording electrode. In the second group of
consecutive patients (Group B), surgery was performed using multiple
recording electrodes.
Surgery
The patient was withdrawn from antiparkinsonian drugs for 36
hours before the scheduled surgery. While the patient received a local
anesthetic, the stereotactic procedure was performed using a CRW
stereotactic frame (NeuroPlan; Radionics, Ghent, Belgium). The target
was determined from fused computed tomographic (CT) and mag-
netic resonance images with the following coordinates: 11 to 12 mm
lateral to the anterior commissure-posterior commissure line, at the
mid-commissural point, and 4 mm inferior to the intercommissural
line. Special attention was given to the trajectory planning for all
patients to avoid blood vessels during electrode installation. After
making a precoronal burr hole, recording electrodes were introduced.
In Group A patients, a single semi-microelectrode (Model RAD SME-
E; Radionics) was introduced 10 mm above the presumed target for
electrophysiological recordings (Neuromap; Radionics). Recordings
were performed in steps of 0.5–1 mm, usually to 4 or 5 mm below the
target. The STN was characterized by a neuronal firing pattern con-
sisting of increased baseline activity and a strong increase in high-
voltage spikes, which were usually present over a length of 4 to 5 mm
(Fig. 1A). Subsequently, the electrode was withdrawn and another
electrode for test stimulation was introduced (Model TC 112;
Radionics).
Intraoperative macrostimulation was initiated with a frequency of
100 Hz and a stimulus duration of 0.1 millisecond. This was continued
stepwise every 2 mm, from 4 mm above the target to 4 mm below the
target. At each step, the stimulus intensity was increased at increments
of 0.5 V until the desired response was achieved or until unwanted side
effects occurred. At each point of test stimulation, the clinical response
was evaluated by the neurologist. The following clinical parameters,
using the Unified Parkinson Disease Rating Scale (UPDRS), were
scored: tremor (if present) and rigidity in all four extremities, finger
taps, hand movements and/or handgrips, and leg agility. If a clinical
response was not present at or several millimeters below the target, the
electrode was withdrawn, and a second target through a different tra-
jectory was chosen, 2 mm anterior, posterior, medial, or lateral to the
FIGURE 1. A, a representative image of electrophysiological activity
measured by a single semi-microelectrode during STN DBS surgery. The
upper trace is 4 mm above target (thalamic activity), the middle trace is
1 mm under target (typical STN activity), and the lower trace is 7 mm
below target (substantia nigra pars reticulata [SNr] activity). B and C,
representative images of electrophysiological activity measured by five
simultaneously implanted microelectrodes; central electrode (B) and pos-
terior electrode (C). In both trajectories, STN activity is indicated (black
line). Typically, STN activity is characterized by a neuronal firing pattern
consisting of increased baseline activity and a strong increase in high-volt-
age spikes, which are usually present over a length of 3 to 6 mm.
AB
C

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Neuropsychological and Psychiatric Evaluations
All patients underwent neuropsychological and psychiatric evalua-
tion preoperatively and at 3 months and 1 year postoperatively in the
on-phases. The neuropsychological evaluation was based on a selection
of standard neuropsychological tests often performed on patients with
PD. If available, alternate forms were used at follow-up time points to
reduce practice effects. The selection included the following tests.
Controlled Oral Word Association Test
The Controlled Oral Word Association Test (18) consists of three
word-naming trials. During 1 minute, the patient must name as many
words as possible beginning with a given letter. The total score is the
number of correct words provided in 3 minutes. Alternate versions
were used at follow-up.
Semantic Fluency
In the Semantic Fluency test (16), the patient must name as many
words as possible belonging to animal and occupational categories
within 1 minute. The total score is the number of correct words pro-
vided in 2 minutes.
California Verbal Learning Task (Dutch Version)
The California Verbal Learning Task (6) affords an analysis of learn-
ing and retention and is specifically designed to assess the use of
semantic associations. In the present study, raw scores are used and are
based on five learning trials of a 16-word list, including four categories
(total score per trial, 1–5), a free trial for long delay (delayed reproduc-
tion), and recognition of the target words presented with distractors,
including words from an interference list. We used alternate forms of
this test at follow-up.
Recognition Memory Test
We used the nonverbal form of the Recognition Memory Test (22),
which contains 50 stimulus items (male faces) followed by a recogni-
tion trial that pairs the target with 50 distractors. Retention is assessed
immediately after the presentation. Raw scores range from 0 to 50.
Stroop Color Word Test
The Stroop Color Word Test (19) measures perceptual interference,
response inhibition, and selective attention by having the subject 1)
read color names, 2) name colors, and 3) name the ink color used on
words that are printed in a nonmatching color (the interference trial).
The test is scored by measuring the time to complete each trial and the
number of errors in the interference trial.
Psychiatric evaluations involved open interviews with the patient
and family members to discuss and observe clinically significant
changes in behavior. Additionally, the Dutch version of the Beck
Depression Inventory (2nd edition) (1) was completed to assess the
existence and severity of depression. This edition of the Beck
Depression Inventory includes a self-report measure of 21 items. Each
item deals with a particular aspect of depression and contains four
statements of graded severity (four-point scale ranging from 0 for
absence to 3 for most severe). Total scores range from 0 to 63, with
scores higher than 20 indicating moderate to severe depression.
Statistical Analysis
Data are presented as means and standard deviations. The changes
in motor parameters between baseline (preoperative), 3 months postop-
eratively, and 1 year postoperatively were analyzed using repeated-
measures analysis of variance with time as the within-subjects factor
initial target. When a good effect was identified with the absence of
side effects, the test electrode was replaced by the final quadripolar
electrode (Model 3389; Medtronic, Minneapolis, MN), with the second-
deepest pole at the level of the best clinical result.
In the patients of Group B, normally five microelectrodes were
simultaneously implanted (Leadpoint; Medtronic). When the trajec-
tory planning had shown it to be impossible to avoid a blood vessel
when using five electrodes, then four or, if necessary, fewer electrodes
were used. Recordings were performed in 0.5–1-mm steps from 10 mm
above the target, usually until 4 to 5 mm below the target. The electrode
with the most typical STN pattern (Fig. 1, B and C) over the longest dis-
tance was selected for test stimulation. This microelectrode was
retracted until its tip was hidden, and the tip of its outer cannula,
designed for test stimulation, was installed at 4 mm above the target.
The other four (or fewer) electrodes were left in place but retracted for
20 mm. Stimulation was performed in the same way as for Group A.
When we obtained a positive clinical result without unwanted side
effects, the electrode was withdrawn and replaced by the quadripolar
electrode while the other four electrodes were temporarily left in place
to maximize the correct positioning (“anchoring effect”) of the final
electrode. When we encountered an unsatisfying clinical effect, another
electrode was chosen for test stimulation.
In both patient groups, the position of the final electrodes was veri-
fied using fluoroscopy. This electrode was finally fixed in the burr hole
with methylmethacrylate and connected to an extension cable, which
was externalized at a distance of approximately 7 cm from the burr
hole, and connected to an external pulse generator (Model 3625;
Medtronic). The same procedure was performed on the contralateral
side. On the second postoperative day, all patients underwent CT imag-
ing to evaluate the relative position of the electrodes and to detect
(a)symptomatic bleedings or other complications. The images were
evaluated by an independent neuroradiologist. When 1 week of eval-
uation with test stimulation showed a clear effect on parkinsonian
symptoms, a second operation was performed under general anesthe-
sia, to implant the pulse generator infraclavicularly or abdominally
(Itrell III or Kinetra; Medtronic).
To compare the duration of surgery for both groups, we recorded
this information for all patients.
Motor Evaluations
Disease stage was assessed using Hoehn and Yahr scores, activities
of daily living (ADL) were evaluated using the UPDRS, Part II, and
motor performance was evaluated using the UPDRS, Part III. The
complications of drug therapy were evaluated using the UPDRS, Part
IV score. These scores were evaluated preoperatively, 3 months post-
operatively, and 1 year postoperatively. Evaluations were performed
in the best medication-on and practically defined medication-off
phases, with both stimulators on and off for 12 hours as described by
the Core Assessment Program for Intracerebral Transplantation for
PD (12). This resulted in four experimental conditions. All data were
collected by the same investigators in the same sequence, and the
patient as well as the investigator were aware of the status of the med-
ication and stimulation.
Medication
Medication intake was defined by the L-dopa equivalent dose, which
equals 100 mg of L-dopa or 133 mg of L-dopa modified-release prepa-
rations or 1 mg of pergolide, 10 mg of bromocryptine, 1 mg of cabergo-
line, 6 mg of ropinirole, 1 mg of lisuride, 1 mg of pramipexol, or 20 mg
of apomorphine. A stable level of medication was maintained for at
least 2 months before surgery.
ONS348 | VOLUME 61 | OPERATIVE NEUROSURGERY 2 | NOVEMBER 2007
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and group as the between-subjects factor. For assessments performed
in on- and off-phases, these analyses were repeated for each phase for
each clinical parameter. For neuropsychological parameters, change
scores were calculated by distracting the scores at baseline from those
at 3 months and 1 year postoperatively. These scores were analyzed
using nonparametric tests (Mann-Whitney U test). A P value of less
than 0.05 was considered to be statistically significant for all analyses.
All data were analyzed using SPSS-pc, version 12.0.1 software (SPSS,
Chicago, IL).
RESULTS
Patient Characteristics
Fifty-five patients suffering from advanced PD who under-
went bilateral STN stimulation were included in this study
(Table 1). Group A consisted of 32 patients (21 men and 11
women) and Group B consisted of 23 patients (15 men and 8
women). The mean age of the patients at the time of surgery
was 59.4 years in Group A and 64.6 years in Group B. The
mean disease durations were 13.1 and 11.3 years for Groups A
and B, respectively. The preoperative Hoehn and Yahr stage in
the medication-on phase was similar in both groups.
In Group A, three patients died due to an unrelated cause,
and in Group B, one patient died and one patient went for
follow-up to another hospital.
Details of Surgery
While making the electrophysiological recordings, we
observed typical STN activity on the right side over a length of
4.7 ? 1.5 mm in Group A and of 4.8 ? 1.5 mm in Group B. On
the left side, the heights of STN activities were 4.1 ? 1.5 mm
and 4.8 ? 0.9 mm in Groups A and B, respectively. The differ-
ences between the groups were not statistically significant (F
test, ?3.6; not significant).
In Group A, a mean of 1.5 ? 1.0 trajectories (range, 1–5 trajec-
tories) for the right STN and 1.3 ? 0.8 trajectories (range 1–5 tra-
jectories) for the left STN were necessary to find a satisfactory
effect on macrostimulation. In Group B, five microelectrodes were
used for simultaneous electrophysiological recordings except for
three patients. In these patients, one electrode (typically the
medial electrode) was excluded because of a blood vessel that
was observed during trajectory planning and could not be
avoided despite adjustment of the stereotactic angles. In the right
STN, the trajectory chosen for implantation of the final quadripo-
lar electrode was the central trajectory for 36% of the patients
(8 patients), the anterior trajectory for 27% of the patients (6
patients), the lateral trajectory for 23% of the patients (5 patients),
the posterior trajectory for 9% of the patients (2 patients), and the
medial trajectory for 5% of the patients (1 patient). For implanta-
tion of the final quadripolar electrode in the left STN, we chose
the central trajectory in 32% of the patients (7 patients), the ante-
rior trajectory in 27% of the patients (6 patients), the lateral trajec-
tory in 18% of the patients (4 patients), the posterior trajectory in
14% of the patients (3 patients), and the medial trajectory for 9%
of the patients (2 patients).
All patients experienced at least a 50% improvement of their
key symptom(s) (akinesia, rigidity, or tremor) during intraop-
erative macrostimulation.
Duration of Surgery
The duration of surgery was equal in both groups (F test,
1.20; not significant). In Group A, the mean duration of surgery
from skin incision to skin closure was 5.38 hours ? 52.5 min-
utes (range, 3.43–7.05 hours), and in Group B, mean duration
was 5.37 ? 1.37 hours (range, 2.43–8.47 hours).
Activities of Daily Living
Bilateral STN stimulation improved the total UPDRS, Part II
score by 36.2% in Group A(F test, 22.39; P ? 0.01) and by 35.4%
in Group B (F test, 22.44; P ? 0.01) in the medication-off phase
at 3 months postoperatively. At 1 year postoperatively, these
improvements were 31.7% (F test, 14.34; P ? 0.01) and 44.0% (F
test, 9.93; P ? 0.05) in Groups A and B, respectively. The
changes in the UPDRS, Part II score after 3 months and 1 year
were not different between Groups Aand B (F tests, ? 0.80; not
significant) in the medication-off phase (Tables 2 and 3).
In the medication-on phase, there were small improve-
ments in the total UPDRS, Part II score in both groups at 3
months and 1 year postoperatively (Tables 2 and 3). These
improvements were not statistically significant (F tests, 2.2;
not significant).
Motor Functions: UPDRS, Part III
Bilateral STN stimulation improved the total UPDRS, Part III
score in the medication-off phase by 44.5% (F test, 28.7; P ? 0.01)
in Group A and by 56.5% (F test, 46.1; P ? 0.01) in Group B at 3
months postoperatively (Tables 2 and 3). The improvements at 1
year postoperatively in the medication-off phase were 40.9% (F
test, 28.2; P ? 0.01) and 55% (F test, 107.3; P ? 0.01) in Groups A
and B, respectively. The total UPDRS, Part III score was signifi-
cantly more improved in patients of Group B compared with
patients in Group Aat 1 year postoperatively (F test, 4.2; P?0.05).
TABLE 1. Patient characteristics for 55 patients suffering from
advanced Parkinson’s disease who were included in the study
CharacteristicGroup AGroup B
Sex (no.)
Male
Female
Age at surgery (yr)
Mean ? standard deviation
Range
Disease duration (yr)
Mean ? standard deviation
Range
Hoehn and Yahr stage, pre-
operative, medication-on
Mean ? standard deviation
Range
21
11
15
8
59.4 ? 7.0
43–75
64.6 ? 9.6
43–79
13.1 ? 5.1
8–21
11.3 ? 5.6
3–21
2.7 ? 1.2
2–5
2.7 ? 0.6
2–5
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Concerning the individual items in the UPDRS, Part III
score, at 3 months postoperatively there were significant
improvements in rigidity (Group A: F test, 8.07; P ? 0.05;
Group B: F test, 28.81; P ? 0.01), akinesia (Group A: F test,
29.35; P ? 0.01; Group B: F test, 14.35; P ? 0.01), bradykinesia
(Group A: F test, 18.31; P ? 0.01; Group B: F test, 23.40; P ?
0.01), freezing (Group A: F test, 19.24; P ? 0.01; Group B: F test,
6.12; P ? 0.05), and gait (Group A: F test, 49.65; P ? 0.01;
Group B: F test, 6.26; P ? 0.05) in both groups in the medica-
tion-off phase. However, reduction in tremor was only signif-
icant in Group B (F test, 5.31; P ? 0.05). At 1 year postopera-
tively, again rigidity (Group A: F test, 32.19; P ? 0.01; Group B:
F test, 33.78; P ? 0.01), akinesia (Group A: F test, 11.62; P ?
0.01; Group B: F test, 13.96; P ? 0.01), bradykinesia (Group A:
F test, 25.79; P ? 0.01; Group B: F test, 16.67; P ? 0.01), freez-
ing (Group A: F test, 4.75; P ? 0.05; Group B: F test, 6.58; P ?
0.05), and gait (Group A: F test, 45.08; P ? 0.01; Group B: F test,
9.26; P ? 0.05) were significantly improved in the medication-
off phase. Improvement of tremor was only significant in
Group B (F test, 12.25; P ? 0.01). The improvements in tremor
(F tests ? 4.74; P ? 0.05) and rigidity (F tests ? 3.86; P ? 0.05)
were significantly greater in Group B compared with Group A
at both 3 months and 1 year postoperatively.
In the medication-on phase, the total UPDRS, Part III score
improved by 40.0% (F test, 13.56; P ? 0.01) and by 33.7% (F test,
13.31; P ? 0.01) at 3 months postoperatively in Groups A and
B, respectively. At 1 year postoperatively, these improvements
were 22.2% (F test, 4.86; P ? 0.05) and 28.9% (F test, 6.86; P ?
0.05) in Groups A and B, respectively. These improvements
were similar in both groups (F tests ? 2.85; not significant).
In the medication-on phase, bilateral STN stimulation
improved rigidity (Group A: F test, 5.41; P ? 0.05; Group B: F
test, 22.99; P ? 0.01), bradykinesia (Group A: F test, 7.77; P ?
0.01; Group B: F test, 4.92; P ? 0.05), and akinesia (Group A: F
test, 9.33; P ? 0.01; Group B: F test, 13.62; P ? 0.05) at 3 months
postoperatively. Tremor was significantly reduced only in
Group B (F test, 10.78; P ? 0.01). At 1 year postoperatively, the
items rigidity (Group A: F test, 15.22; P ? 0.01; Group B: F test,
7.52; P ? 0.05) and bradykinesia (Group A: F test, 4.92; P ? 0.05;
Group B: F test, 9.48; P ? 0.05) showed a significant improve-
ment. Tremor was similar to 3 months postoperatively, only
significantly reduced in Group B (F test, 16.04; P ? 0.01).
Complications of Drug Therapy: UPDRS, Part IV
The total UPDRS, Part IV score was improved by 74.8% (F
test, 57.24; P ? 0.01) and 80.7% (F test, 17.23; P ? 0.01) at 3
aUPDRS, Unified Parkinson Disease Rating Scale; ns, not significant.
TABLE 2. Changes in Unified Parkinson Disease Rating Scale scores for Group A with bilateral subthalamic nucleus deep brain
stimulationa
3 Months Postoperatively
Score
1 Year Postoperatively
Score
Scoring factor Baseline Score
P valueP value
Medication-off
UPDRS, Part II
UPDRS, Part III total
Tremor
Rigidity
Akinesia
Bradykinesia
Freezing
Gait
Medication-on
UPDRS, Part II
UPDRS, Part III, total
Tremor
Rigidity
Akinesia
Bradykinesia
Freezing
Gait
UPDRS, Part IV
Medication: L-dopa
22.1 ? 7.2
41.1 ? 13.9
3.4 ? 4.2
8.8 ? 5.2
15.4 ? 5.5
2.5 ? 1.2
2.3 ? 2.1
2.2 ? 0.9
14.1 ? 7.4
22.7 ? 14.7
2.6 ? 3.8
5.1 ? 4.4
7.7 ? 4.8
1.4 ? 1.3
0.8 ? 0.9
1.2 ? 1.2
?0.01
?0.01
ns
?0.05
?0.01
?0.01
?0.01
?0.01
15.1 ? 8.6
24.3 ? 13.6
2.7 ? 3.8
4.8 ? 3.3
8.8 ? 5.5
0.9 ? 1.2
1.2 ? 1.9
0.8 ? 1.2
?0.01
?0.01
ns
?0.01
?0.01
?0.01
?0.05
?0.01
10.5 ? 7.7
18.5 ? 10.2
1.7 ? 3.9
4.7 ? 3.8
6.2 ? 3.8
0.9 ? 0.8
0.6 ? 0.8
0.9 ? 0.6
6.6 ? 3.5
840.2 ? 400.1
8.7 ? 4.6
11.1 ? 6.0
0.8 ? 1.4
2.5 ? 2.4
3.1 ? 2.7
0.5 ? 0.6
0.3 ? 0.6
0.6 ? 0.8
1.7 ? 1.6
ns10.3 ? 4.7
14.4 ? 6.8
0.9 ? 1.5
2.5 ? 2.9
5.0 ? 4.3
0.5 ? 0.7
0.4 ? 0.8
0.5 ? 0.8
1.2 ? 1.6
490.5 ? 339.2
ns
?0.01
ns
?0.05
?0.01
?0.01
ns
ns
?0.01
?0.05
ns
?0.01
ns
?0.05
ns
ns
?0.01
?0.01

Page 6

months postoperatively, and by 81.6% (F test, 17.23; P ? 0.01)
and 90.6% (F test, 14.28; P ? 0.01) at 1 year postoperatively in
Groups A and B, respectively (Tables 2 and 3). These improve-
ments in Groups A and B were similar (F tests ? 0.31; not
significant).
Medication: L-dopa Equivalent Dose
Bilateral STN stimulation resulted in a profound decrease of
the L-dopa equivalent dose of 49.8% (F test, 50.27; P ? 0.01) and
41.7% (F test, 38.81; P ? 0.01) in Group A and of 49.0% (F test,
26.26; P ? 0.01) and 54.4% (F test, 15.29; P ? 0.01) in Group B
at 3 months and 1 year after surgery, respectively (Tables 2 and
3). These reductions were not statistically different between
Groups A and B (F tests ? 0.44; not significant).
Active Contacts and Stimulation Parameters
In 26 patients (81.1%) of Group A, the contact at the level of
the target was activated on the right side (Fig. 2). In four
(12.5%) patients, the contact above target, in one patient, the
contact at two levels above target, and in one patient, the con-
tact below target was activated on the right side. On the left
side in Group A, the following was activated: in 24 patients
(75%) the target contact, in 4 patients (12.5%) the contact
above target, in 2 patients the contact at two levels above tar-
get, and in 2 patients the contact below target.
For Group B, these distributions on the right side were as fol-
lows: in 17 patients (73.9%), the contact at the level of the tar-
get, in 4 patients (17.3%), the contact above target, in 1 patient,
the contact at 2 levels above target, and in 1 patient, the contact
below target. On the left side, again in 17 patients (73.9%) the
target contact was activated, in 4 patients (12.5%) the contact
above target was activated, in one patient the contact at two
levels above target was activated, and in one patient the contact
below target was activated. The distribution of active contacts
between the groups was not significantly different.
At 3 months postoperatively, the mean stimulation settings
for patients in Group A were 180 and 180 Hz, 2.2 and 2.6 V,
and 108.8 and 112.5 microseconds for channels 1 (left STN)
and 2 (right STN), respectively. The majority of the patients
received monopolar stimulation. For Group B, these settings
were 156.9 and 156.9 Hz, 2.2 and 2.4 V, and 90 and 101.6
microseconds for channels 1 and 2, respectively. In this group,
the majority of the patients received monopolar stimulation as
well. At 1 year postoperatively, these parameters were gener-
ally comparable to the settings used at 3 months (Table 4).
There were no statistically significant differences between the
aUPDRS, Unified Parkinson Disease Rating Scale; ns, not significant.
TABLE 3. Changes in Unified Parkinson Disease Rating Scale scores for Group B with bilateral subthalamic nucleus deep brain
stimulationa
3 Months Postoperatively
Score
1 Year Postoperatively
Score
Scoring factorBaseline Score
P value P value
Medication-off
UPDRS, Part II
UPDRS, Part III total
Tremor
Rigidity
Akinesia
Bradykinesia
Freezing
Gait
Medication-on
UPDRS, Part II
UPDRS, Part III, total
Tremor
Rigidity
Akinesia
Bradykinesia
Freezing
Gait
UPDRS, Part IV
Medication: L-dopa
19.8 ? 7.0
45.1 ? 13.7
5.6 ? 4.4
11.1 ? 5.9
14.1 ? 6.1
2.3 ? 1.3
1.9 ? 1.7
1.5 ? 1.3
19.6 ? 10.6
19.6 ? 10.6
3.3 ? 2.2
3.0 ? 2.9
7.1 ? 3.9
0.7 ? 0.9
1.0 ? 1.3
0.8 ? 1.0
?0.01
?0.01
?0.05
?0.01
?0.01
?0.01
?0.05
?0.05
11.1 ? 7.7
20.3 ? 10.2
3.9 ? 1.2
2.8 ? 3.7
8.6 ? 5.3
0.4 ? 0.7
0.7 ? 1.1
0.8 ? 1.2
?0.05
?0.01
?0.01
?0.01
?0.01
?0.01
?0.05
?0.05
12.8 ? 5.8
24.9 ? 12.9
5.9 ? 5.1
6.6 ? 4.6
9.6 ? 5.2
1.2 ? 1.1
1.3 ? 2.1
1.0 ? 0.8
6.2 ? 3.1
798.4 ? 475.2
11.5 ? 8.6
16.5 ? 8.4
2.6 ? 2.4
1.9 ? 1.8
5.8 ? 3.9
0.6 ? 0.7
0.8 ? 1.2
0.6 ? 0.9
1.2 ? 1.5
ns 11.1 ? 7.7
17.7 ? 9.4
3.0 ? 1.5
2.3 ? 2.5
6.2 ? 4.9
0.3 ? 0.6
0.6 ? 1.0
0.4 ? 0.8
0.6 ? 0.7
364.9 ? 354.5
ns
?0.01
?0.01
?0.01
?0.01
?0.05
ns
ns
?0.01
?0.05
ns
?0.01
ns
?0.05
ns
ns
?0.01
?0.01
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TEMEL ET AL.
groups with respect to stimulation settings (F tests ? 0.72;
not significant).
Behavior: Neuropsychological
and Psychiatric Evaluations
Fifty patients completed neuropsychological assessment at
baseline and at 3 months follow-up, and 45 patients completed
follow-up assessment at 1 year after surgery. The groups did
not differ in education level (median, 5; range, 1–7), but
patients in Group A were younger than those in Group B (Z,
–2.05; P ? 0.05). The neuropsychological tests scores of both
groups are shown in Table 5. There were no significant differ-
ences at baseline on the neuropsychological tests except for let-
ter fluency, with Group A scoring higher than Group B (Z,
–2.14; P ? 0.05).
At 3 months after surgery, significant differences were
identified between the groups in changed scores on tests for
mental speed and verbal memory, including the total score
on the five-trial presentation of a 16-word list and the
delayed (free) reproduction. Patients in Group B needed
more time to name colors than those in Group A (Z, –2.64;
P ? 0.05). With respect to verbal memory, patients in Group
A showed an increase in number of words learned, whereas
patients in Group B showed a decrease in number of words
learned (Z, –3.25; P ? 0.01). Also for the delayed reproduc-
tion, Group A showed an increase in number of words repro-
duced, whereas Group B showed a decrease in number of
words reproduced (Z, –3.25; P ? 0.01).
One year after surgery, there were significant differences
between the groups in changes from baseline on both verbal
and nonverbal memory tests. Patients in Group Aagain showed
an increase in the number of words learned and reproduced,
whereas patients in Group B showed a decrease in both number
of words learned (Z, –3.48; P ? 0.01) and reproduced (Z, –2.92;
P ? 0.01). At 1 year follow-up, there was also a significant dif-
ference in the recognition trial, with patients in Group Ashow-
ing an improvement and patients in Group B showing a decline
in the number of words recognized (Z, –2.69; P ? 0.05). Finally,
patients in Groups A and B differed significantly in changes
from baseline on a nonverbal memory test. Patients in Group A
showed an increase in the number of faces recognized, whereas
patients in Group B showed a decrease in number of faces rec-
ognized (Z, –2.54; P ? 0.05). Subsequent analysis revealed that
the above-mentioned differences between Groups Aand B were
not related to the age differences.
There was no significant difference in changes from base-
line, both at 3 months and one year postoperatively, on a self-
report questionnaire for depression. The patients in Group A,
however, showed a trend toward a decrease in self-reported
depression at 1 year after surgery compared with patients in
Group B (Z, –1.92; P ? 0.06).
Individual psychiatric evaluation revealed clinically signifi-
cant changes in behavior. After surgery, seven patients (22%) in
Group A and four patients (19%) in Group B suffered from
depressive symptoms, and one patient (3%) in Group A and
four patients (19%) in Group B experienced (hypo)manic symp-
toms. Furthermore, in Group A, one patient (3%) reported
symptoms of hypersexuality, and another patient reported
aggressiveness. Three patients in Group B (14%) reported
symptoms of passiveness.
Surgery- and Hardware-Related Complications
There were no postoperative hemorrhages or epileptic
attacks in patients of Groups A or B. In the first three patients
in Group B, the postoperative CT scan showed a pneumoen-
cephalus with a thickness of more than 1 cm. One of these
patients showed a decrease in consciousness for approximately
40 minutes at the end of the surgery, and improved at the time
of the CT scan.The other two patients did not present with any
sign of raised intracranial pressure. Two patients of Groups A
and B developed a local hardware-related infection around the
implanted pulse generator and the extension cable. Two were
successfully treated with antibiotic therapy, whereas the other
two required additional removal of the infected extension
FIGURE 2. Distribution of active electrode contacts in Groups A and B
on the right and left sides. The contact at the level of the target is indicated
by 0; 1 is the electrode contact above target, 2 is the electrode contact at two
levels above target (the most proximal electrode contact of the 3389 elec-
trode), and –1 is the contact below target (the most distal electrode contact
of the 3389 electrode).

Page 8

cables and pulse generators. After subsequent antibiotic
therapy, new pulse generators and extension cables were
implanted. Nine patients (four from Group A and five from
Group B) showed immediate postoperative confusion, which
resolved with conservative treatment in several hours to days.
We found no correlation between postoperative confusion and
neuropsychological outcome.
DISCUSSION
After its first application in patients in 1993 (17), STN DBS is
presently considered the treatment of choice for patients suffer-
ing from advanced PD (as outlined by the American
Association of Neurological Surgeons). In the last 13 years, the
technique of DBS in general and STN DBS in particular has
undergone several adaptations, especially with regard to imag-
ing and intraoperative neurophysiology, to enhance both effi-
cacy and safety. The simultaneous implantation of five micro-
electrodes in the form of an orthogonal cross with the central
electrode directed toward the target was developed to obtain a
three-dimensional representation of the STN. The STN can be
functionally divided into three parts, including an anterodorso-
laterally located motor part, a more ventromedially located
associative part, and a smaller, most medially located limbic
part (20). The target for STN DBS in PD is located in the
anterodorsolateral motor part, to obtain the best possible
results for motor symptoms and reduce the risk for behavioral
complications. An intraoperative, three-dimensional, neuro-
physiological mapping of the STN would lead to better identi-
fication of the borders of this small nucleus on the basis of the
length of the typical STN pattern recorded by the five respec-
tive electrodes. This in turn will promote better identification of
the anterodorsolateral part.
The results of the present study show that the simultaneous
implantation of multiple electrodes does not increase the risk of
bleeding or any other major intracranial complication. The first
three patients we operated on with intraoperative, three-
dimensional electrophysiological mapping showed a pneu-
moencephalus bifrontally with a thickness of more than 1 cm
on the postoperative CT scan. Refining the burr hole (with a
smaller diameter and a better positioning of the patient, at the
highest level of the head), led to a disappearance of this com-
plication in subsequent patients. We also found that this proce-
dure does not necessarily increase the duration of surgery as
compared to the procedure performed with a single recording
electrode. This is important for the comfort of both the patient
and the surgeon.
The use of multiple electrodes resulted in better motor results
when compared with patients who underwent STN DBS
guided with a single recording electrode. Patients in Group B
had significantly more improvement of tremor and rigidity,
and as a consequence they also had a better total UPDRS, Part
III score during the medication-off phase as compared with
patients in Group A. The fact that only in 32% (left side) and
36% (right side) of the patients was the central trajectory cho-
sen for final electrode placement means that in the majority of
the patients, less than optimal effect would have been obtained
when only one recording or test electrode was used.
Despite better motor effects, patients in Group B showed
deterioration in neuropsychological functions, and more specif-
ically, deterioration in memory functions. At 3 months follow-
up, patients in Group Aimproved on both verbal learning and
delayed verbal reproduction, whereas patients in Group B
showed deterioration on both measures. At 1 year follow-up,
there was still a significant difference between the groups in the
change from baseline on both learning and delayed reproduc-
tion in favor of Group A. Additionally, at this time point, we
also found that patients in Group A showed an increase in
recognition of both words and faces, whereas patients in Group
B showed a decrease in verbal and nonverbal recognition. With
respect to clinically significant psychiatric changes, in both
groups, similar amounts of affective symptoms are reported. In
TABLE 4. Mean stimulation settings for all patients at 3 months and 1 year postoperatively
Group AGroup B
Characteristic3 Months 1 Year 3 Months1 Year
Stimulation frequency (Hz)
Channel 1
Channel 2
Stimulation amplitude (V)
Channel 1
Channel 2
Pulse width (?s)
Channel 1
Channel 2
Stimulation polarity, monopolar/bipolar
Channel 1
Channel 2
180.0 ? 0
180.0 ? 0
172.2 ? 19.6
171.3 ? 20.6
156.9 ? 25.9
156.9 ? 25.9
161.8 ? 25.2
161.8 ? 25.2
2.2 ? 1.0
2.6 ? 1.2
2.4 ? 1.3
3.4 ? 1.1
2.2 ? 0.8
2.4 ? 0.9
2.5 ? 1.1
2.7 ? 0.9
108.8 ? 53.0
112.5 ? 52.6
94.4 ? 12.0
94.4 ? 12.0
90.0 ? 12.2
101.6 ? 19.5
103.6 ? 38.8
103.6 ? 28.0
26/6
24/8
25/7
24/6
19/4
21/2
21/2
19/4
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TEMEL ET AL.
Group B, however, more patients suffered from (hypo)manic
features and passiveness. A microlesion effect could be a pos-
sible explanation for the difference in neuropsychological func-
tioning, in favor of the single-electrode group; when five elec-
trodes at a time are implanted within the STN, the chance is
greater that at least one will be located in the non-motor part
and thus can give rise to a postoperative lesion effect related to
associative and limbic functions. There are two counterargu-
ments for this microlesioning effect. First, this reduced neu-
ropsychological functioning in Group B is still present after
1 year, and second, the tips of the microelectrodes are so small
(diameter, 20–25 μm), that a lesioning effect is unlikely. One
could argue that the use of two or three simultaneously placed
microelectrodes could prevent the deterioration of neuropsy-
ans, Not significant.
TABLE 5. Neuropsychological tests scores for both groups studieda
Characteristic Group AGroup BP value
Stroop
Word(s)
Change at 3 months
Change at 1 year
Color(s)
Change at 3 months
Change at 1 year
Color word(s)
Change at 3 months
Change at 1 year
Color word errors
Change at 3 months
Change at 1 year
California Verbal Learning Task
Total score from Trials 1–5
Change at 3 months
Change at 1 year
Delayed reproduction
Change at 3 months
Change at 1 year
Recognition
Change at 3 months
Change at 1 year
Recognition Memory Test: faces
Change at 3 months
Change at 1 year
Controlled Oral Word Association Test
Letter fluency
Change at 3 months
Change at 1 year
Category fluency
Change at 3 months
Change at 1 year
Beck Depression Inventory
Change at 3 months
Change at 1 year
50.5 ? 12.6
2.3 ? 8.6
4.0 ? 11.0
67.6 ? 15.2
2.3 ? 11.1
6.7 ? 16.1
113.8 ? 30.9
10.4 ? 31.0
20.5 ? 34.3
2.4 ? 3.2
0.7 ? 2.9
1.5 ? 4.4
54.1 ? 12.6
6.2 ? 8.6
4.0 ? 15.2
69.5 ? 13.3
10.5 ? 8.8
12.0 ? 11.9
127.7 ? 37.6
30.8 ? 49.1
25.4 ? 19.1
3.6 ? 5.2
4.5 ? 8.4
5.4 ? 8.74
ns
ns
?0.05
ns
ns
ns
ns
ns
47.1 ? 10.0
1.6 ? 7.7
4.7 ? 10.0
9.3 ? 3.2
1.5 ? 2.7
1.6 ? 3.1
14.4 ? 1.6
0.4 ? 2.0
0.6 ? 2.0
41.1 ? 4.9
1.1 ? 4.6
3.0 ? 4.0
47.5 ? 9.5
–7.5 ? 9.1
–6.8 ? 5.3
9.5 ? 2.3
–1.4 ? 2.8
–1.2 ? 2.0
15.1 ? 1.2
–0.4 ? 1.5
–0.9 ? 1.0
39.0 ? 4.4
–0.3 ? 4.4
–0.9 ? 4.4
?0.01
?0.01
?0.01
?0.01
ns
?0.05
ns
?0.05
37.8 ? 11.3
–3.3 ? 8.6
–3.9 ? 10.2
37.8 ? 11.4
–4.0 ? 5.9
–3.0 ? 7.9
11.8 ? 6.6
–4.4 ? 8.2
–3.7 ? 6.9
33.2 ? 11.1
–5.1 ? 8.9
–3.6 ? 9.3
33.9 ? 8.8
–4.6 ? 6.7
–3.9 ? 6.5
9.2 ? 7.1
–3.1 ? 6.9
1.4 ? 8.2
ns
ns
ns
ns
ns
ns

Page 10

chological functions. This would be a compromise between the
two techniques. In the present study, only in 1 out of 23 patients
in Group Awere 3 simultaneously placed microelectrodes used
for electrophysiological recording. The other patients had five,
and few had four simultaneously placed microelectrodes.
Future investigation is necessary to determine whether such a
compromise could be made and be effective in preventing neu-
ropsychological decline.
The nonrandomized nature of this study may be a possible
limitation. A randomized setup of the study would be pre-
ferred from a methodological point of view. However, when
we started this study, the use of electrophysiology was
strongly debated, and we first wanted to confirm the safety of
electrophysiology in DBS. Therefore, we operated on the first
group of patients using electrophysiological recordings
through a single electrode, and we did not perform a random-
ized trial. After the process appeared to be safe, we proceeded
to multiple-electrode-guided DBS and compared the effects as
outlined here.
An important question is, to what extent do these neuropsy-
chological results undermine the motor effects, in other words,
to what extent are these neuropsychological results clinically
relevant? We performed open interviews with patients and
partners. Mainly symptoms of depression, (hypo)mania, and
passiveness were reported as relevant by the patient and fam-
ily. Nevertheless, patients and caregivers should be aware of all
of these behavioral changes, even if the clinical impact of some
appears to be small.
CONCLUSION
The use of simultaneously implanted multiple electrodes for
electrophysiological recording to guide STN DBS is a safe proce-
dure and produces improved motor outcome. The subtle changes
in neuropsychological function need special consideration.
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COMMENTS
T
patients, including one who received limited microelectrode recording
(MER) and one who underwent simultaneous five-channel MER
recording. Temel et al. show that motor outcomes are slightly better in
the latter, but that neuropsychological side effects at 1 year are slightly
worse. This study adds information to the debate regarding optimal
strategy for MER. There are methodological issues inherent to nonran-
domized studies; for example, the effect of surgeon experience could
account in part for the results. Nevertheless, the results are thought-
provoking. Multiple simultaneous MERs are relatively safe from the
standpoint of hemorrhagic stroke, as reported in this as well as other
studies. However, more brain penetrations cannot be made with total
impunity. This motivates the search for methods of DBS implantation
that reduce the number of brain penetrations while preserving high
levels of accuracy and precision.
his article compares the outcome and complications of subthalamic
nucleus (STN) deep brain stimulation (DBS) in two groups of
Philip A. Starr
San Francisco, California
T
emel et al. address an interesting question in this article, namely, in
patients undergoing placement of electrodes for DBS, is there a dif-
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underwent multiple simultaneous MERs. Design problems, statisti-
cal weaknesses, and lack of bias controls enfeeble the veracity of the
conclusions.
It is important to note that the patients who had surgery with the
semi-microelectrode were earlier patients in the series, and those with
multiple simultaneous microelectrode tracks were the later patients.
This makes any late improvements more difficult to interpret. Was the
improvement in motor outcome secondary to the new technique or
was it a result of better patient selection and targeting based on previ-
ous experience? It also makes findings concerning the risk of bleeding
difficult to assess. Specifically, was there no increased risk of bleeding
in the second group of patients because multiple tracks do not increase
risk or because the blood pressure and perioperative medications with
anticoagulant properties were more tightly controlled with the authors’
increased experience and recognition of risk factors that may be asso-
ciated with intracranial hemorrhage (2)?
The negative findings, i.e., greater impairment on memory testing
in the later group of patients, is more noteworthy, as these patients
benefited from the authors’ earlier experiences yet still had the effect.
Why this occurred remains unclear. The second group was older, yet
covariate analysis excluded age as a confounding variable. Age has
been shown to correlate with a decline in executive functions in these
patients (5). Other possibilities include increased injury with multiple
tracks to the limbic and associative areas of the STN or to the substan-
tia nigra (4). The mean number of penetrations in Group A was 1.5,
whereas 20 of 23 patients had 5 tracks in Group B. There is mounting
evidence that STN DBS may lead to impaired performance on cogni-
tive testing (4, 6, 9). Multiple microelectrodes that pass through the
sensorimotor areas of the STN have not been reported to show signif-
icant injury in autopsy specimens (3). It is possible that multiple
tracks through the caudate or in the associative region of the STN
may be the source of these adverse effects. It is also possible that this
finding is an epiphenomenon.
As systems capable of multiple simultaneous MERs become increas-
ingly available, the question becomes, how many tracks are truly war-
ranted? Advocates of MER presently determine the number of tracks
based on intraoperative data collected. The decision of subjecting
patients to five tracks automatically, especially in light of the potential
effects on cognitive outcome, should not be taken lightly. As the
authors note, one potential compromise that we prefer is the use of
three tracks rather than five. Of course, clinicians would need to deter-
mine which three tracks and the relative positioning of those tracks
based on variable orientations of the x–y stage. This article is a timely
contribution to the literature and provides data that may influence
daily practice.
Julie G. Pilitsis
Roy A.E. Bakay
Chicago, Illinois
1. Amirnovin R, Williams ZM, Cosgrove GR, Eskander EN: Experience
with microelectrode guided subthalamic nucleus deep brain stimulation.
Neurosurgery 58[Suppl 1]:ONS96–ONS102, 2006.
2. Binder DK, Rau GM, Starr PA: Risk factors for hemorrhage during microelec-
trode-guided deep brain stimulator implantation for movement disorders.
Neurosurgery 56:722–732, 2005.
3. Counelis GJ, Simuni T, Forman MS, Jaggi JL, Trojanowski JQ, Baltuch GH:
Bilateral subthalamic nucleus deep brain stimulation for advanced PD:
Correlation of intraoperative MER and postoperative MRI with neuropatho-
logical findings. Mov Disord 18:1062–1065, 2003.
ference in terms of efficacy and safety between the use of single or
multiple microelectrodes?
This study included only patients with medically refractory
Parkinson's disease who had bilateral STN electrodes placed. This facil-
itated matching of the two groups and the data analysis. There were 55
patients overall; of these, 32 patients (Group A) had surgery guided by
a single semi-microelectrode, whereas in Group B (23 patients) an array
of (usually) 5 microelectrodes was placed simultaneously. Patients were
assessed before surgery and at 3 and 12 months after surgery, with
assessments of overall Unified Parkinson's Disease Rating Scale
(UPDRS) as well as components of the UPDRS relating to activities of
daily living (UPDRS II), motor functions (UPDRS III), and complica-
tions of medical therapy (UPDRS IV). Psychiatric and neuropsychi-
atric evaluations were also done. Patients were assessed for any
changes in postoperative medication requirements and for stimulation
parameters.
Surgical technique and duration were essentially the same in both
groups, except for the difference in the microelectrodes. In Group A, a
mean of 1.5 electrode passes were made (range, 1–5). In Group B, in
about one-third of the patients, an electrode other than the central one
was used (in conjunction with macrostimulation control) to choose the
path of the implanted electrode. This indicates that the multiple
electrode array was of use in identifying the ideal final target. Post-
operative computed tomography scans ruled out significant hemor-
rhage in all patients.
UPDRS evaluations showed improvements in activities of daily liv-
ing, motor function, medication requirements, and complications of
drug therapy in both groups. Stimulation parameters were equivalent.
Comparison between the two groups showed a relative benefit for
Group B only in tremor and rigidity in the medication-off phase.
Neurospsychiatric testing identified a decrease in verbal and nonverbal
memory in Group B. These patients were also 5 years older on average,
although their disease duration was 2 years shorter. Similar numbers of
patients had depression after surgery, whereas there was a trend
toward increased hypomania in Group B.
Temel et al. have added evidence to the literature indicating that
microelectrode recording affects placement of subthalamic stimulators
and is not associated with an increased risk of hemorrhage. The mixed
clinical outcomes (improved motor scores with a decline in neuropsy-
chiatric testing results) clearly warrant additional study and prevent
this article from being a ringing endorsement of multiple microelec-
trode arrays for DBS placement.
Michael Schulder
Manhassett, New York
T
patients who had surgery guided by simultaneously implanted mul-
tiple microelectrodes. They found that there was no difference in
complication rates. Patients with simultaneously implanted multiple
microelectrodes had significantly better medication-off motor out-
comes as assessed by UPDRS III, but worse neuropsychological out-
comes on tests of verbal and nonverbal memory at 1 year. The mul-
tiple microelectrode systems are attractive because of the potential
time-saving ramifications, although the authors show no difference
in operating room time between the groups. The article is well writ-
ten and timely, as more systems that simultaneously implant multi-
ple microelectrodes are becoming commonplace and available (1, 7,
8). The results of this study warn of the potential for greater impair-
ment on neuropsychological tests of memory in the group that
emel et al. compared their results from 32 patients who under-
went surgery guided by a single semi-microelectrode and 23
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Deep brain stimulation: Postoperative issues. Mov Disord 21 [Suppl 14]:
S219–S237, 2006.
5. Funkiewiez A, Ardouin C, Caputo E, Krack P, Fraix V, Klinger H, Chabardes
S, Foote K, Benabid AL, Pollak P: Long term effects of bilateral subthalamic
nucleus stimulation on cognitive function, mood, and behaviour in
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6. Kleiner-Fisman G, Herzog J, Fisman DN, Tamma F, Lyons KE, Pahwa R, Lang
AE, Deuschl G: Subthalamic nucleus deep brain stimulation: Summary and
meta-analysis of outcomes. Mov Disord 21 [Suppl 14]:S290–S304, 2006.
7. Levy R, Lozano AM, Hutchison WD, Dostrovsky JO: Dual microelectrode
technique for deep brain stereotactic surgery in humans. Neurosurgery 60
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8. Moyer JT, Danish SF, Keating JG, Finkel LH, Baltuch GH, Jaggi JL: Imple-
mentation of dual simultaneous microelectrode recording systems during
deep brain stimulation surgery for Parkinson’s disease: Technical note.
Neurosurgery 60[Suppl 1]:ONSE177–ONSE178, 2007.
9. Smeding HM, Speelman JD, Koning-Haanstra M, Schuurman PR, Nijssen P,
van Laar T, Schmand B: Neuropsychological effects of bilateral STN
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NEUROSURGERY
VOLUME 61 | OPERATIVE NEUROSURGERY 2 | NOVEMBER 2007 | ONS357
GUIDED ELECTRICAL STIMULATION IN PARKINSON’S DISEASE
Illustration of a transsphenoidal procedure for pituitary disorders (1912), by Max Brödel for Cushing’s publication, “Surgical
Experiences with Pituitary Disorders,” in The Journal of the American Medical Association, Volume LXIII, 1914. From Crosby RW,
Cody J: Max Brödel: The Man who put Art into Medicine. New York, Springer-Verlag, 1991.