Surgical Movement Disorders

Surgical Treatment of
Movement Disorders
Benzi M. Kluger, MDa,*, Olga Klepitskaya, MDa, Michael S. Okun, MDb,c
KEYWORDS
Movement disorders Surgical treatment
Deep brain stimulation Parkinsons disease
Dystonia Essential tremor
The past 2 to 3 decades have been marked by a resurgence in surgical approaches for
the treatment of movement disorders, specifically the creation of neuroanatomical
lesions and deep brain stimulation (DBS). This renewed interest has been spurred
on by several factors including (1) improvements in our understanding of the neurophysiology and anatomy of movement disorders, (2) the refinement of DBS as
a surgical approach, (3) improvements in neurosurgery and neuroimaging, which
have enhanced our ability to localize brain structures, and (4) an increasing role for
surgical interventions, especially in circumstances in which current pharmacologic
treatments have reached their limits. Appropriate patient selection for surgery can
result in a compelling treatment option for a variety of movement disorders, with the
most common to date including Parkinsons disease (PD), dystonia, and essential
tremor.
HISTORY
Surgical treatments for movement disorders can be traced to the late 1800s and early
1900s where applications included lesions placed in the motor cortex,1 the corticospinal tracts,2 and the cerebral peduncles.3 Early attempts at therapy were focused
mainly on treating hyperkinetic movement disorders, including tremor. Not surprisingly, these early treatments had an unacceptable rate of side effects, particularly of
motor weakness. With the introduction of the stereotactic head frame technology in
This work was supported by an American Academy of Neurology Foundation Clinical Research
Training Fellowship (B.M.K.), and the National Parkinson Foundation Center of Excellence,
Gainesville, FL.
a
University of Colorado Denver and Health Sciences Center, Academic Office 1 mailstop B185,
PO Box 6511, Aurora, CO 80045, USA
b
Department of Neurology, University of Florida, 100 S. Newell Dr, Room L3-100, PO Box
100236, Gainesville, FL 32610, USA
c
University of Florida Movement Disorders Center, McKnight Brain Institute, 100 S. Newell Dr.
Room L3-100, PO Box 100236, Gainesville, FL, USA
* Corresponding author.
E-mail address: benzi.kluger@ucdenver.edu (B.M. Kluger).
Neurol Clin 27 (2009) 633677
doi:10.1016/j.ncl.2009.04.006
neurologic.theclinics.com
0733-8619/09/$ see front matter 2009 Elsevier Inc. All rights reserved.
634
Kluger et al
the late 1940s by Spiegel and colleagues,4 targeting very small subcortical structures
became a more realistic possibility. However, there was still a paucity of basic or clinical scientific evidence to know which nodes of this circuitry would be most appropriate for surgical interventions. A breakthrough in our understanding came in 1953,
when Cooper accidentally ligated the anterior choroidal artery during a pedunculotomy,
and this dramatically improved his patients tremor. The ligation interrupted the main
blood supply to many structures in the basal ganglia, including the globus pallidus,
a finding confirmed by pathologic examination of some of Coopers5 similar but later
cases. Although this procedure was abandoned as a result of unacceptable side
effects, and because of difficulty in reproducing Coopers success, it was followed
by more refined surgical approaches that focused largely on many subcortical structures. In 1955, Hassler6 reported that thalamotomy was more effective than pallidotomy for tremor. Cooper subsequently endorsed this surgical approach, adding that
results of thalamotomy were more consistent than those of pallidotomy. In 1960,
Svennilson and colleagues7 reported that the clinical results of pallidotomy were location dependent, with posterior lesions demonstrating superior results to anterior
lesions. Although this article demonstrated that posteroventral pallidotomy improved
all the cardinal motor signs of PD, this research did not influence general clinical practice, which continued to favor the thalamotomy. In 1963, a few authors published
results suggesting that subthalamotomy may obtain tremor improvement similar to
that with thalamotomy.8 However, the fear of inducing hemiballism and subsequent
reports showing clinical improvements in only a minority of patients with subthalamotomy led to thalamotomy being the procedure of choice.9 The introduction of levodopa
in 1967 for the treatment of PD provided a remarkable therapeutic benefit, which
initially threatened to make all surgical approaches to PD obsolete.10
The 1980s brought a renewed interest in surgical approaches for movement disorders, beginning with the use of thalamotomy for severe drug-resistant tremor.11 In
1992 Laitinen and colleagues12 replicated Leksells benefits for posteroventral pallidotomy in all cardinal PD motor signs, and in 1997, Gill and Heywood13 reported their
results of bilateral subthalamotomy. This renewed interest in surgery was driven largely
by an increased recognition of the limitations of long-term levodopa therapy. Equally
important were advances made in our understanding of basal ganglia circuitry and
physiology,14 including the emergence of animal models of basal ganglia disease.15
In 1987, Benabid and colleagues16 observed that high-frequency electrical stimulation to the ventral intermediate (VIM) nucleus of the thalamus, usually performed as
part of neurosurgical localization, could be left in place and have dramatic chronic
effects in improving tremor. This observation fueled the further development of
DBS as a means of treating basal ganglia disorders. Although there are no
adequately powered trials published to date comparing DBS to lesion therapy,
DBS has virtually supplanted surgical lesions mainly due to its reversibility, flexibility
in changing settings, and its improved tolerability in patients requiring bilateral
surgical treatment (eg, avoiding speech and swallowing problems). We focus on
DBS in this review, recognizing that the efficacy and general principles of lesion
therapy are similar and that there may be cases in which ablative surgery may be
advantageous.18
MECHANISMS OF ACTION
Ablative brain lesions seem to achieve their functional improvement through the
disruption of aberrant network activity. The pioneering work of Delong14 and Albin
and Young17 in describing the direct and indirect pathways as well as the parallel
Surgical Treatment of Movement Disorders
circuitry of the basal ganglia circuitry has laid the foundation for identifying potential
regions where surgical interventions may improve symptoms. PD is known to result
in increased firing rates and changes in the pattern of activity of both the globus pallidus interna (GPi) and subthalamic nucleus (STN).19 These patterns have been
confirmed in humans by physiologic recordings from PD patients undergoing DBS
or ablative surgery.20 Moreover, ablative lesions within the GPi and STN appear
to somewhat normalize this abnormal physiologic activity and are associated with
functional improvements.15
Although DBS appears to produce an informational lesion (a term coined by Grill)
that may mimic many of the effects from ablative surgery, the physiologic mechanisms
are thought to be more complex.21 In simple terms, DBS is thought to work by inhibiting cells close to the stimulating electrode and by exciting passing fiber tracts, but this
simplistic model does not consider many of the complex changes that may contribute
to DBS effects. There is currently evidence to support the existence of several potential sites of action including the following:
1. Inhibition of neuronal cell bodies in close proximity to the electrode. Evidence from
primate recordings demonstrates a reduction in firing rates of cells adjacent to
stimulation electrodes during therapeutic stimulation of both STN and GPi.22 This
reduction in firing rate may be due to a depolarization block through alterations
of potassium or sodium channels and/or alterations in the balance of presynaptic
excitatory and inhibitory afferents.23 Depolarization blockade as a singular mechanism has fallen out of support of most experts in the field.
2. Stimulation of axons in close proximity to the electrode. In fact, studies have shown
increased output from an inhibited nucleus, which is believed to be due to action
potentials initiated via axonal stimulation.24 This activity is time locked to the stimulator frequency. Computer models have further suggested that the therapeutic
efficacy of STN is strongly linked to axonal activation.25
3. Stimulation of fiber tracts passing through the field of stimulation. DBS currents
sufficient for axonal activation may spread beyond the anatomic target to adjacent
fiber tracts. Several tracts important to basal ganglia functioning pass in close
proximity to the STN and have been hypothesized to contribute to the clinical effect
of DBS, including cerebellothalamic fibers (tremor reduction), nigrostriatal tracts
(increase striatal dopamine release), and the zona incerta (all cardinal motor
symptoms).23
4. Alterations in neurotransmitter release and synthesis. As noted above, activation of
the nigrostriatal tract may increase striatal dopamine release. Other microdialysis
studies of STN DBS in rats have demonstrated modulatory effects on both glutamate and g-aminobutyric acid release within basal ganglia circuits.26
5. Alterations in network dynamics. DBS may interrupt pathologic neural output by
providing stimulation greater than a neurons spontaneous activity and thus preempting intrinsic firing. This has been referred to as an informational lesion,
because it replaces irregular pathologic activity with regular but informationally
neutral output.21 Functional imaging studies have demonstrated changes in
multiple nodes of the motor circuitry, including the motor cortex, supplementary
motor area (SMA) and cerebellum with symptom improvement following DBS.
6. Chronic network changes. As discussed in the section on dystonia, many clinical
improvements take days to weeks, suggesting that they are dependent on neuroplastic changes. Consistent with this concept, studies have demonstrated longterm changes in synaptic plasticity following DBS.27 There is also preliminary
evidence to suggest that DBS may confer some neuroprotective effects.28
635
636
Kluger et al
These mechanisms are not mutually exclusive, and it appears likely that the therapeutic effects of DBS are the result of multiple mechanisms.26 Moreover, there is
evidence that the mechanisms of DBS may not be identical across disease states,29
subcortical targets,30 or stimulation parameters.31
SELECTION OF SURGICAL CANDIDATES
The evolution of DBS therapy has resulted in the acceptance that selection of appropriate patients is critically important to the therapeutic benefit. In fact, only a small
subset of patients (10%20%) may be appropriate at any one time.32 Currently,
patients with PD, dystonia, and essential tremor (ET) may be considered surgical
candidates after they have failed medical management (DBS is Food and Drug Administration approved for these indications in the United States). Patients must be motivated and have the resources available to participate in the extensive follow-up
required to program and monitor the DBS device. In addition, potential candidates
must have an acceptable risk benefit ratio favoring surgery. All indications (PD, ET,
and dystonia) for DBS carry risks, especially with comorbidities such as age, cognitive
dysfunction, frailty, psychiatric disease, cerebral atrophy, blood thinners, and especially hypertension. Among dystonia patients, primary and/or tardive dystonia seems
to have the best response, whereas patients with other forms of secondary dystonia,
including structural changes or neurometabolic diseases, tend to have less-predictable responses to DBS.33 However, an increasing number of successes may be
seen in these secondary dystonias with appropriate selection of target and stimulus
parameters.34 In PD, patients and clinicians should be aware that DBS will potentially
benefit only symptoms that are levodopa responsive.35 DBS can improve on time,
reduce on-off fluctuations, and decrease dyskinesias but, with the exception of
tremor, does not provide motor benefits that exceed the patients best on medication state (with the current available targets of STN or GPi). It is thus critical for potential PD DBS candidates to have the Unified Parkinson disease rating scale (UPDRS)
completed in both the practically defined on and off states. In general, clinics
should follow the Core Assessment Program for Surgical Intervention Therapies in
PD criteria, which include a minimal disease duration of 5 years, a diagnosis of idiopathic PD, screening for depression and cognitive decline, and assessment for
minimal motor improvement of 30% based on UPDRS scores.35 One exception to
this 30% rule is medically refractory tremor in PD, which may occur in 20% or more
patients. There is currently insufficient evidence to support the use of early DBS
in any movement disorder, although considerations are being explored in research
arenas, including effects on quality of life (QOL), decreased surgical mortality (vs delayed operations), cost savings, and the possibility that DBS may have a diseasemodifying effect.36 Caution is required in how we define early disease, particularly
in patients without significant disability, patients who have not received adequate trials
of standard medications, and in patients with short disease duration who may not have
a definitive diagnosis.
Although potential surgical candidates may be identified by general neurologists,
the decision to proceed through surgery is in the best circumstances made by an
experienced multidisciplinary/interdisciplinary team typically including a movement
disorders neurologist, neurosurgeon, psychiatrist, neuropsychologist, and, in some
circumstances, a social worker, speech therapist, occupational therapist, and/or
physical therapists (Fig. 1).37 Each member of the multidisciplinary team should
have a specific role in this evaluation and should contribute to a discussion by the
team regarding the diagnosis, scale changes, expectations of benefit, risk, financial
Fig. 1. Multidisciplinary team.
issues, QOL, target choice, staged versus simultaneous implantation if bilateral

devices may be required, and the ability of the patient to meet the schedule of
follow-up appointments. The neurologist must ensure that patients have been
correctly diagnosed and that they present with symptoms likely to respond to DBS.
They must have exhausted medical options and their symptoms carefully quantified
with appropriate disease-specific scales (eg, on/off UPDRS for PD, tremor rating scale
[TRS] for ET, and Burke-Fahn-Marsden dystonia rating scale [BFMDRS]). In the case
of PD, it is recommended that the patient have at least 5 years of symptoms as it is
frequently difficult to distinguish levodopa-responsive parkinsonian syndromes that
may be manifesting in early stages. The Florida Surgical Questionnaire for Parkinsons
Disease (FLASQ-PD) was developed as a screening questionnaire to aid in the identification of surgical candidates with PD (Box 1).37 It is important that the neurologist
appropriately educates the patient, because unrealistic expectations regarding the
benefits and convenience of DBS are a frequent cause of patients perception of
DBS failure. As discussed later, significant nonmotor complications, including
mood, cognition, and speech, may occur following DBS and may be in part preventable through the appropriate screening of high-risk patients.38 There is some evidence
that younger patients (younger than 70 years) may have less risk of cognitive complications; however, this is not an absolute rule, and many older patients have excellent
outcomes following DBS.
STIMULATOR PLACEMENT AND PROGRAMMING
The accurate localization of DBS targets requires a combination of high-quality neuroimaging, stereotactic localization (frameless or frame-based), and physiologic recordings. The superior resolution of subcortical structures evident on magnetic resonance
imaging (MRI) has resulted in its use as the primary imaging modality at most centers.
Many centers fuse computed tomography with MRI images to save time on the day of
surgery (by performing the MRI the day before) and postoperatively to localize lead
637
638
Kluger et al
Box 1
FLASQ-PD
A. Diagnosis of idiopathic Parkinsons disease
Diagnosis 1: Is Bradykinesia present? Yes/No (Please circle response)
Diagnosis 2: (check if present):
Rigidity (Stiffness in arms, leg, or neck)
46 Hz resting tremor
Postural instability not caused by primary visual, vestibular, cerebellar, proprioceptive
dysfunction
Does your patient have at least 2 of the above? Yes/No (Please circle response)
Diagnosis 3: (check if present):
Unilateral onset
Rest tremor
Progressive disorder
Persistent asymmetry affecting side of onset most
Excellent response (70%100%) to levodopa
Severe levodopa-induced dyskinesia
Levodopa response for 5 y or more
Clinical course of 5 y or more
Does your patient have at least 3 of the above? Yes/No (Please circle response)
(Yes answers to all 3 questions above suggest the diagnosis of idiopathic PD)
B. Findings suggestive of Parkinsonism due to a process other than idiopathic PD
Primitive reflexes
1- RED FLAGpresence of a grasp, snout, root, suck, or Myersons sign
N/Anot done/unknown
Presence of supranuclear gaze palsy
1- RED FLAGsupranuclear gaze palsy present
N/Anot done/unknown
Presence of ideomotor apraxia
1- RED FLAGideomotor apraxia present
N/Anot done/unknown
Presence of autonomic dysfunction
1- RED FLAGpresence of new severe orthostatic hypotension not due to medications,
erectile dysfunction, or other autonomic disturbance within the first year or 2 of disease
onset
N/Anot done/unknown
Presence of a wide-based gait
1- RED FLAGwide-based gait present
N/Anot done/unknown
Presence of more than mild dementia
1- RED FLAGfrequently disoriented or severe cognitive difficulties, severe memory

problems, or anomia
N/Anot done, not known
Presence of severe psychosis
1- RED FLAGpresence of severe psychosis, refractory to medications
History of unresponsiveness to levodopa
1- RED FLAGParkinsonism is clearly not responsive to levodopa, patient is dopamine
nave, or patient has not had a trial of levodopa
(Any of the FLAGs above may be contraindications to surgery)
positions. There is, however, even under the best circumstances, a chance for clinically significant errors from stereotactic targeting, frame shift, brain shift, or misinterpretation of microelectrode recordings (MER). Suboptimal lead placement by even
a few millimeters may result in an unacceptable outcome. It should be noted that
most DBS targets, including the thalamus (VIM), STN and GPi, have a somatotopic
and functional organization that includes sensorimotor, cognitive (associative), and
limbic regions. In fact, nonmotor regions have been estimated to make up roughly
one-third of each target.39 To ensure the accurate placement of DBS leads (or lesions)
into the sensorimotor region of the intended target structure, most institutions will
perform clinical examinations in the conscious patient and MER to ensure that they
are within the correct region of their target site. Macrostimulation, which follows
MER, involves delivering test stimulation with the actual DBS electrode. Macrostimulation may identify target areas on the basis of acute symptom improvement, and it
may also clarify mislocalization on the basis of common side effects usually seen
with the stimulation of nearby structures. Examples may include reports of phosphenes with stimulation in the region of the optic tract or muscle twitches or pulling
with stimulation of the internal capsule. Some centers rely primarily on macrostimulation and do not routinely perform MER. MER involves the passage of a small micrometer-size recording tip (usually platinum iridium or tungsten) into the target region. As
the microelectrode passes through various brain structures, the neurologist or physiologist can identify the relevant brain structures, including white matter and deep
brain nuclei, on the basis of their unique firing rates and patterns of activity. These
data may be supplemented by passive and active movements of the limbs and facilitate the identification of inhibition or driving activity that may define sensorimotor territories. Oscillatory activity may also be identified and correlated to a patients tremor.
Although MER and macrostimulation data may aid the accuracy of DBS placement,
there also may be some risk to using multiple passes through cerebral structures to
generate a 3-dimensional representation that guides localization.40,41 These risks
may include a slightly higher rate of hemorrhage (especially in patients with uncontrolled hypertension) and cognitive or mood side effects, most prominently postoperative confusion, particularly when operations are performed in a simultaneous
bilateral, as opposed to staged, procedure. Although there are 3 general techniques
used for MER (target verification, multiple pass mapping, and Ben-Gunn),41 these
techniques have not been compared with regard to their risks or efficacy. Similarly,
639
640
Kluger et al
Table 1
Deep brain stimulation complications
Summary of Adverse Events
Event
No. of Patients (%)
Intraoperative
Vasovagal response
8 (2.5)
Syncope
4 (1.2)
Severe cough
3 (0.9)
IVH
2 (0.6)
ICH
2 (0.6)
Arrhythmia (junctional rhythm)
1 (0.3)
Confusion
1 (0.3)
Extreme anxiety
1 (0.3)
Laceration of soft palate
1 (0.3)
TIA
1 (0.3)
Perioperative (within 2 wk)

Headache
48 (15.0)
Confusion
16 (5.0)
Hallucination
9 (2.8)
Nausea/vomiting
5 (1.6)
Seizure
4 (1.2)
Dysarthria
3 (0.9)
Dyskinesia
2 (0.6)
Hypertension
2 (0.6)
Paranoia
2 (0.6)
Paresthesia
2 (0.6)
Sore throat
2 (0.6)
TIA
2 (0.6)
Urinary retention
2 (0.6)
Angina
1 (0.3)
Arrhythmia (right bundle branch block)
1 (0.3)
Deep vein thrombosis
1 (0.3)
Depression
1 (0.3)
Dizziness
1 (0.3)
Insomnia
1 (0.3)
Pulmonary edema
1 (0.3)
SDH (evacuated)
1 (0.3)
Long-term (2 wk)
Infection
14 (4.4)
Cognitive dysfunction
13 (4.0)
Dysarthria
13 (4.0)
Worsening gait
12 (3.8)
Agitation
5 (1.6)
Paresthesia
4 (1.2)
Depression
3 (0.9)
Headache
2 (0.6)
(continued on next page)
Table 1
(continued)
Summary of Adverse Events
Event
No. of Patients (%)
Psychogenic tremor
2 (0.6)
Urinary incontinence
2 (0.6)
Blepharospasm
1 (0.3)
Emotional lability
1 (0.3)
Insomnia
1 (0.3)
Metallic taste
1 (0.3)
Suicide
1 (0.3)
Data from Kenney C, Simpson R, Hunter C, et al. Short-term and long-term safety of deep brain
stimulation in the treatment of movement disorders. J Neurosurg 2007;106:6215.
more research is needed to determine if staged or simultaneous procedures have

distinct advantages and in which populations they should be applied.
SURGICAL AND DBS COMPLICATIONS
DBS complications may be divided into risks associated with the surgical procedure
and chronic complications of therapy that may or may not be device related. The
most serious complications associated with DBS surgery are cerebrovascular accidents (including transient ischemic events) (0.9%), intracranial hemorrhage (1.2%),
seizure (1.2%), device infection (4.4%), lead fracture (3.8%), and device movement
or misplacement (3.2%),42 and the risks vary from study to study depending on
many factors. Many centers do not prospectively assess adverse events, and this
may lead to under-reporting.43 These risks may be somewhat attenuated by appropriate screening and treatment of comorbid conditions, including hypertension,
which increases hemorrhage risk during MER; diabetes, which increases the risk
of infection; psychiatric disease, which increases the risk of depression and suicide;
cognitive deficits, which increase the risk of postoperative confusion; and obesity or
other significant cardiopulmonary diseases, which may increase the general risk of
surgery.44,45
Complications of DBS may also occur following the acute operative period. These
complications may occur from problems in triage, screening, inadequate patient
counseling/unreasonable patient expectations, operative procedure (including DBS
misplacement), medication adjustments, or device programming difficulties. In a series
of patients seeking further management after suboptimal DBS outcomes, the most
common reasons for poor DBS outcome/DBS failure included inadequate screening
(no movement disorder neurologist or documented neuropsychological testing)
(66%), inappropriate or missed diagnosis (22%), suboptimally placed electrodes
(46%), inadequate programming follow-up (17%) or suboptimal DBS parameters
(37%), and suboptimal medication management (73%).38 Of the patients seen in
this series, two-thirds had good outcomes (51%) or modest improvement (15%) after
receiving appropriate interventions. Chronic side effects may occur in patients even
when the device has been appropriately placed, and lead settings may be optimized
for the greatest symptomatic benefit. Side effects may be stimulation related and may
be reversible with a simple change in settings. However, some side effects may be due
to microlesional effects of the DBS placement and thus not amenable to changes in
641
642
Kluger et al
Table 2
Summary of STN and GPi DBS outcomes for PD
Author, Year
Type
Target
Duration
(mo)
Krack et al.,
1997101
27
Prosp NC
STN
112
NA
Ghika et al.,
1998102
Prosp NC
GPi
24
Krack et al.,
1998103
Retrosp NC
STN
UPDRS III
Motor
LE
NA
22/17
22.7%
63/28
55.6%
N/A
N/A
20/8
60.0%
31/10
67.7%
38/28
26.3%
66/33
50.0%
1080/960
11.1%
3.5/2.5
28.6%
7.9/4.6
41.8%
33.3/9.1
72.7%
4.0/1.4
65.0%
13.6/
10.6
22.0%
27.8/
15.0
46.0
57.5/
17.1
70.3%
53.6/
32.5
39.4%
1156/681
41.1%
GPi
18.2/
14.7
19.2%
23.2/
26.5
14.0%
865/1110
28.3%
4.8/1.2
75.0%
N/A
26.0%
40.0%
N/A
27.0%
41.0%
Unchanged
30.0%
UPDRS II ADL
LID
Comments
Kumar et al.,
1998104
8
6
Prosp NC
Prosp NC
GPi
STN
3
3
Kumar et al.,
1998105
Prosp DB
STN
10.5/
12.4
18.1%
28.1/
19.7
29.9%
30.1/
17.7
41.2%
55.7/
19.4
65.2%
40.0%
1.8/0.3
83.3%
Limousin et al.,
1998106
20
Prosp NC
STN
12
N/A
60.0%
10.0%
60.0%
1224/615
49.8%
11.0/7.7
30.0%
Decreased speech
fluency;
Dysarthria
Improvement of
executive function
(marginal)
Decreased off time from
40% to 10%
60.0%
41.0%
S&E off 29.0/73.2

( 152.4%)
Off time 2.2/0.6 (72.7%)
FBA 39.6/37.4 (5.6%)
Volkmann et al.,
1998107
Prosp NC
GPi
Ardouin et al.,
1999108
26
Prosp
STN
Burchiel et al.,
1999109
Prosp DBl
STN
12
N/A
78.0%
N/A
Prosp DBl
GPi
12
N/A
63.0%
Limousin et al.,
1999110
73
Prosp NC
Th
12
N/A
Moro et al.,
1999111
Prosp NC
STN
16
Pinter et al.,
1999112
Prosp NC
STN
20.6/8.4
59.2%
33.9/
19.4
42.8%
54.1/
23.9
55.8%
767/675
12.0%
NS
2.6/0.4
84.6%
Weight gain
ADL improved Decrease
in verbal fluency
S&E off 52.2/83.9
( 60.7%)
Stable results in 6, 9 and
12 mo
44.0%
51.0%
N/A
N/A
39.0%
Unchanged
11.6/3.8
67.2%
9.5/5.0
47.4%
13.85/
9.24
33.3%
N/A
37.0/
25.7
30.5%
649/610
(LD)
2.0/1.5
25.0%
S&E 72.35/82.77
( 14.4%)
15.3/
14.3
6.5%
36.1/
17.3
52.1%
29.3/
30.7
-4.8%
67.6/
39.3
41.9%
1507/521
65.4%
Reduced
Sleep improved
Weight gain 13%
Neuropsychological
testing unchanged
11.6/9.1
21.6%
29.6/
12.6
57.4%
24.1/
18.8
22.0%
60.0/
27.8
53.7%
527/133
74.8%
2.9/0.5
82.8%
STN
12
11.6/9.3
19.8%
29.6/
12.8
56.8%
24.1/
18.8
22.0%
60.0/
27.1
53.8%
527/211
60.0%
S&E off
47.5/82.5 ( 73.7%)
Off time decreased 8.8/
1.0 (88.6%)
S&E off 47.5/80.0 0.
( 68.4%)
55.4/
19.8
64.3%
N/A
Bejjani et al.,
2000113
12
Prosp NC
STN
N/A
N/A
78.0%
64.0%
70.0%
83.0%
Motor fluctuations
88.0%
Houeto et al.,
2000114
23
Prosp NC
STN
11/2
81.8%
30/10
66.7%
N/A
N/A
1340/820
38.8%
7.0/1.6
77.1%
Fluctuation
4.5/1.0 (77.8%)
12.6/4.8
61.9%
643
644
Kluger et al
Table 2
(continued)
Author, Year
Type
Target
Duration
(mo)
Jahanshahi
et al., 2000115
NC (on/off)
STN
226
UPDRS II ADL
UPDRS III
Motor
LE
LID
Comments
62.7/25.1
60.0%
GPi
Improves some aspects

of executive
functioning
54.2/27.2
49.8%
Molinuevo
et al., 2000116
15
Prosp NC
STN
N/A
26.7/7.5
71.9%
N/A
49.6/16.9
65.9%
1338/262
80.4%
Pillon, 2000117
48
NC
STN
12
N/A
N/A
N/A
55.4/18.1
67.3%
1110/348
68.6%
15
STN
N/A
N/A
N/A
GPi
12
N/A
N/A
N/A
GPi
N/A
N/A
N/A
56.1/19.4
65.4%
55.4/37.1
33.0%
41.6/27.0
35.1%
1063/465
56.3%
744/873
17.3%
850/735
13.5%
Alegret, 2001118
15
Prosp
STN
N/A
29.9/10.9
63.6%
N/A
53.6/23.2
56.7%
57.9%
Capus, 2001119
Prosp NC
STN
N/A
N/A
20.3%
50.6%
40.7%
80.6%
Off time 89.7%

S&E 38.7/84 ( 117.1%)
H&Y 3.8/1.9 (50.0%)
Improved psychomotor
speed and working
memory
S&E
27.5/72.5 (-163.6%)
H&Y 4.2/2.3 (45.2%)
Moderate deterioration
of verbal memory
73.5%
Motor fluctuations
improvement 57.2%
PDQ38 improvement
49.9%
DBS/PD study
group, 2001120
Prosp DBl
Crossover
STN
11.2/10.2
8.9%
28.4/16.0
43.7%
23.6/17.8
24.6%
54.0/25.7
52.4%
1218/764
37.3%
1.9/0.8
57.9%
38
Same
GPi
12.7/8.8
30.7%
17.9/17.9
0.0%
24.1/16.5
31.5%
50.8/33.9
33.3%
1090/1120
-2.8%
2.1/0.7
66.7%
Prosp NC
STN
Prosp
NC
STN
12
31.55/13.78
56.3%
31.2/14.3
54.2%
22.44/13.44
40.1%
21.6/17.2
20.4%
62.9/32.6
48.2%
65.0/40.5
37.7%
NA
8.66/7.67
11.4%
9.2/7.5
18.5%
5.33/2.22
58.4%
4.33/0.5
88.5%
Slight impairment in
executive function
The same subjects as
those in the previous
group
Faist et al.,
2001122
Prosp NC
STN
15
N/A
N/A
N/A
49.8/7.4
85.1%
N/A
N/A
Improves walking
velocity
Stride length
S&E off 43.7/88.7
( 103.0%)
Lopiano et al.,
2001123
16
Prosp NC
STN
8.8/7.7
12.5%
28.3/9.1
67.8%
20.3/14.8
27.1%
59.8/25.9
56.7%
1162/321
72.4%
3.5/1.1
68.6%
Off time 2.0/0.3 (85%)
Lopiano et al.,
2001124
20
Prosp NC
STN
12
N/A
N/A
19.8/16.8
5.0%
58/25.1
56.7%
954/228
76.1%
Volkmann et al.,
2001125
16
Prosp NC
STN
12
GPi
12
28.8/12.6
56.3%
21.0/12.1
42.4%
15.1/16.4
-8.6%
30.2/16.7
44.7%
56.4/22.4
60.3%
52.5/16.7
68.2%
2.73%
11
13.7/11.0
19.7%
12.1/5.8
52.1%
2.0/0.4
80.0%
2.4/0.4
83.3%
836/605
27.6%
GPi
N/A
N/A
Unchanged
36%
N/A
60%
6
6
6
GPi
GPi
GPi
12
24
36
N/A
N/A
N/A
N/A
N/A
N/A
Unchanged
Unchanged
Unchanged
26%
38%
32%
N/A
N/A
1415/1225
13.4%
30%
20%
40%
Dujardin et al.,
2001121
Durif et al.,
2002126
NA
Off time 49/19%

(percentage of
waking hours)
Off time 37/24%
(percentage of
waking hours)
Neuropsychological
assessment stable
Off time decreased

by 50%
25%
40%
10%
96
645
646
Kluger et al
Table 2
(continued)
Author, Year
Type
Figueiras-Mendez 22 Prosp NC
et al., 2002127
Duration
Target (mo)
STN
UPDRS II ADL
UPDRS III
Motor
LE
LID
Comments
112
16/9
43.8%
30/16
46.7%
24/10
58.3%
2 13/18
91.6%
32.0%
NA
22/7
68.2%
23/12
47.8%
44/14
68.2%
N/A
28.1/0
100.0%
Off time 31/0%

(percentage of
waking hours)
PDQ 39
38.4/22.3 (24.3%)
Nonsurgical
41.3/42.7 ( 3.4%)
9.6/5.8
39.6%
BDI 10.5/8.5 (19.0%)

PDQ 90.3/129 (42.9%)
Just and
Ostergaard,
2002128
11 Prosp NC
STN
Nonsurgical
11/5
54.6%
Lagrange et al.,
2002129
60 Prosp NC
STN
12
11.3/11.4 29.6/23.4
0.1%
21.0%
53.7/24.3 20.3/18.8
54.7%
7.4%
1010/522
48.3%
Loher et al.,
2002130
10 Prosp NC
GPi
12
37.6/24.9 34.9/22.9
33.8%
34.4%
34.7/24.9 63.4/37.5
28.2%
40.8%
1235.5/1300.6 9.8/5.0
5.3%
48.9%
Martinez-Martin
et al., 2002131
17 Prosp NC
STN
N/A
29.53/8.29 N/A
71.9%
Ostergaard et al.,
2002132
26 Prosp NC
STN
12
9.3/6.8
26.9%
25.2/8.5
66.3%
23.5/10.7 51.3/18.3
54.5%
64.3%
1197/964
19.5%
Romito et al.,
2002133
22 Prosp
STN
2436
N/A
31.6/10
68.4%
N/A
1505.9/491.7
67.4%
55.7/20.76 1400/509
62.7%
63.6%
60.2/29.9
50.3%
S&E
Off 28.8/45.0 ( 56.3%)
On 51.0/60.0 (17.6%)
N/A
Off time 1.8/0.3 (83.3%)

PDQL 40.89/20.18
(50.6%)
2.1/0.3
85.7%
Weight increase 75/8 kg

S&E off 49/84 ( 71.4%)
Off periods 1.8/0.3
(83.3%)
Hypophonia
Dysarthria
Improved sleep
S&E off med
24.5/80.0 ( 226.5%)
Simuni et al.,
2002134
12 Prosp NC
STN
12
N/A
N/A
19.3/19.8 43.5/23.0
2.6%
47.1%
1946/875
55.0%
4.2/1.5
64.3%
Thobois et al.,
2002135
18 Prosp NC
STN
STN
12
26.9/12.7
52.8%
26.9/10.7
60.2%
17.9/15.2
15.1%
17.9/13
27.4%
1045/360
35.5%
same
76.0%
14 Prosp NC
5.3/8.1
52.8%
5.3/7.5
41.5%
Vesper et al.,
2002136
38 Prosp NC
STN
12
N/A
N/A
27.7/17.4 48.3/24.9
37.2%
48.4%
900/580
35.5%
3.2/0.9
71.9%
Off time 14.5/6 (58.6%)
Vingerhoets
et al., 2002137
20 Prosp NC
STN
21
N/A
21.0/13.3
37%
N/A
48.8/26.9
44.8%
1135/230
79.7%
4.8/0.4
92%
50% of patients
discontinued
medications
Voges et al.,
2002138
15 Prosp NC
STN
612
N/A
NA
N/A
55.3/22.7
58.9%
909/374
58.9%
NA
S&E off 42/77 ( 83.3%)
Welter et al.,
2002139
41 Prosp NC
STN
10.4/6.6
36.5%
29/11.1
61.7%
14.7/10.6 51.4/18.5
27.9%
64.0%
1459/480
67.1%
2.1/0.2
90.5%
Chen et al.,
2003140
Prosp NC
STN
N/A
N/A
39.0/19.1 65.7/32.8
51.0%
50.0%
N/A
Improved S&E off 22.9/70.0

( 205.7%)
Daniele et al.,
2003141
20 Prosp NC
STN
12
STN
18
10.1/6.2
38.6%
12.4/5.4
56.5%
31.8/8.8
72.3%
33.1/7.4
77.6%
24.0/22.1
7.9%
25.0/17.3
30.8%
58.8/30.9
47.5%
60.8/27.0
55.6%
1395/500
64.2%
1185/535
54.8%
Funkiewiez et al., 50 Prosp NC

2003142
STN
12
N/A
N/A
N/A
N/A
N/A
12/4
67%
BDI 13.9/11.5 (17.3%)

MDRS 136.8/136.7 (0.1%)
FS 40.8/39.5 (3.2%)
Herzog et al.,
2003143
48 Prosp NC
STN
N/A
STN
12
N/A
STN
24
N/A
44.2/21.7
50.9%
43.9/18.7
57.4%
44.9/19.2
57.2%
1425/730
48.8%
42.4%
20
18.7/14.7
21.4%
18.1/12.4
31.5%
19.3/12.4
35.8%
2.6/1.9
26.9%
2.5/0.3
87.0%
2.4/0.3
85.0%
Temporary psychiatric
adverse events
32
22.6/10.7
52.6%
21.6/10.7
49.2%
23.4/13.2
43.2%
44.9/20.2
55.0%
44.9/17
62.1%
91.0%
PDQ 83.2/54.3 (34.7%)

87.7/49.7 (43.3%)
67.8%
Off time 1.6/1.0 (37.5%)

S&E off 39.6/77.5
( 95.7%)
647
648
Kluger et al
Table 2
(continued)
Author, Year
Type
Target
Duration
(mo)
Kleiner-Fisman
et al., 2003144
25
Prosp NC
STN
12
12.1/10.5
13.2%
Krack et al.,
2003145
49
Prosp NC
STN
60 (5 y)
Pahwa et al.,
2003146
33
Prosp NC
STN
19
UPDRS III
Motor
LE
25.8/17.4
32.6%
22.8/19.4
14.9%
50.1/24.6
50.9%
38.0%
46.4%
7.3/14.0
91.8%
30.4/15.6
48.7%
14.3/21.1
47.6%
55.7/25.8
53.7%
1409/518
63.2%
4.0/1.4
65.0%
DRS 136/131 (3.7%)

BDI 15.5/14.9 (3.9%)
FBA 40.4/37.3 (7.7%)
12
N/A
21.1/14.3
32.2%
N/A
43.8/26.5
39.5%
10.4/5.8
44.2%
18/4%
STN
24
11.6/12.8
10.3%
21.1/15.3
27.5%
26.2/24.1
8.0%
41.3/29.8
27.8%
12.4/5.3
57.3%
19/11%
Off time 44/20%

(percentage of
waking hours)
Off time 43/17%
(percentage of
waking hours)
UPDRS II ADL
LID
Comments
Varma et al.,
2003147
Prosp NC
STN
15/14
6.7%
38/25
34.2%
61%
2067/1055
49.0%
44%
Volkmann et al.,
2004148
Prosp NC
Gpi
36
11.3/7.1
37.2%
8.8/10.3
17.1%
20.9/15.5
25.8%
19.5/19.8
1.5%
30.8/13.9
54.9%
22.2/18.7
15.8%
52.8/26.8
49.2%
49.5/38.0
23.2%
870/897
3.1%
961/760
20.9%
1.9/0.6
68.4%
1.0/0.6
40.0%
12
10.0/9.4
6.0%
26.0/17.3
33.5%
17.6/19.7
11.9%
38.4/23.9
37.8%
1364/867
36.4%
2.9/0.7
75.9%
33
10.0/17.2
72.0%
26.0/22.3
14.2%
17.6/22.1
25.6%
38.4/26.5
31.0%
1364/1029
24.6%
2.9/0.9
69.0%
6
Liang et al.,
2006149
27
60
Prosp NC
STN
MMSE 29/29
Off time 1.9/1.2 (36.8%)

S&E off 47.2/72.1
(52.8%)
Off time 1.9/1.1 (42.1%)
S&E off 47.2/66.7
( 41.3%)
Portman et al.,
2006150
20
Prosp NC
STN
12
N/A
N/A
23/20
13.0% NS
46/33
28.3%
1242/751
39.5%
8.8/3.75
57.4%
Derost,
2007151
53
Prosp NC
STN
24
45.0%
24
18.0/15.6
13.3%
18.8/16.7
11.2%
N/A
STN
3.7/8.5
1.3%
5.6/11.1
98.0%
N/A
41.0%
1246/885
28.9%
1308/760
41.9%
3.4/0.7
79.4%
2.7/1.1
59.3%
STN
12
4.5/8.5
88.9%
4.5/12.5
177.8%
23.7/12.5
47.3%
23.7/13.9
41.4%
14.1/12.5
11.3%
14.1/12.5
11.3%
42.2/21.0
50.2%
42.2/19.3
54.3%
1228/470
61.7%
1228/631
48.6%
9.0/1.9
78.9%
9.0/31.1
245.6%
34
Gan et al.,
2007152
36
Prosp NC
36
S&E off 52/72 ( 38.5%)

Off time 10%
DRS 135.9/137.4 (NS)

BDI 12.8/11.6 (NS)
DRS 135.9/135.5 (NS)
BDI 12.8/16.1 (NS)
11
Prosp NC
Gpi
N/A
N/A
12.5/10.4
16.8%
40.6/21.8
46.3%
1182/1216
2.9%
10.5/2.5
76.0%
Schupbach
et al., 2007154
10
Prosp NC
Comp BMT
STN
18
2.3/5.1
121.7%
19.2/12.9
32.8%
NA
69.0%
57.0%
83.0%
DRS 140.5/140.5 (NS)

FBA 48/47.5 (NS)
MADRS 7/3 (improved)
Tir et al.,
2007155
100
Prosp NC
STN
12
9.5/8
15.8%
27.5/19
30.9%
20/14.4
28.0%
50/29
42.0%
1222/721
41.0%
61.0%
Cognitive decline in
7.7%
Depression 18%
Vesper et al.,
2007156
73
Prosp NC
STN
24
N/A
N/A
30/26
13.3%
50/25
50.0%
45.0%
Witjas et al.,
2007157
40
Prosp NC
STN
12
8.8/4.7
46.6%
23.7/13.3
43.9%
11.8/6.9
41.5%
38/12.4
67.4%
1091/460
57.8%
5.6/1.3
76.8%
S&E off 45.3/63.7

(40.6%)
DRS 137.4/136 (-1.0%)
BDI 8.1/6.4 (21.0%)
Rodriques
et al., 2007153
649
650
Kluger et al
Table 2
(continued)
Author, Year
Type
Target
Duration
(mo)
Zibetti et al.,
2007158
36
Prosp NC
STN
12
N/A
24
N/A
10.0/11.5
15.0%
10.0/12.8
28.0%
10.0/18.9
89.0%
Wider et al.,
2008159
50
Prosp NC
STN
24
60
UPDRS II ADL
25.3/9.9
60.9%
25.3/10.3
59.3%
N/A
N/A
N/A
UPDRS III
Motor
N/A
N/A
24.3/26.7
9.9%
24.3/27.7
14.0%
24.3/30.6
25.9%
LE
LID
54.5/25.8
52.7%
54.5/24.1
55.8%
1023/405
60.4%
1023/417
59.2%
47.2/24.8
47.5%
47.2/24.9
47.3%
47.2/33.2
29.7%
1128/195
82.7%
1128/391
65.3%
1128/485
57.0%
Comments
N/A
N/A
Off time 1.55/0.11

(92.9%)
Off time 1.55/0.03
(98.1%)
4.8/0.7
85.4%
4.8/0.8
83.3%
4.8/0.7
85.4%
Abbreviations: BDI, Becks Depression Inventory; BMT, Best medical treatment; DRS, Mattis Dementia rating scale; Dyskinesia, as measured by UPDRS IV-a (motor
complication) or AIMS (abnormal involuntary movements scale); FBA, frontal battery assessment scale; GPi, Globus pallidus part interna; ICH, intracerebral hemorrage; IVH, intraventricular hemorrage; LD, Levodopa dose only; LE, Levodopa equivalent (the method of calculation was not standardized across the studies);
LID, levodopa induced dyskinesias; MADRS, Montgomery and Asberg depression rating scale; MDRS, Mattis Dementia Rating Scale; MMSE, Folstein mini mental
status Examination; NS, nonsignificant; Off and On, applies to the medication state; Off time, Hours per day spent in clinically defined off period (immobile); PDQ,
Parkinson disease quality-of-life questionnaire, total score; Prosp., NC, prospective noncontrolled clinical trial; S&E, Schwab and England disability scale; SDH,
subdural hemorrage; STN, Subthalamic nucleus; Th, Thalamus; TIA, transient ischemic attack; UPDRS IIADL, activities of daily living, maximum 52; UPDRS III,
motor subscore, maximum 108. Results are represented as Preoperative/Postoperative, with the percentage change calculated as: [(Preoperative Postoperative)/Preoperative] 100.
Data from Kenney C, Simpson R, Hunter C, et al. Short-term and long-term safety of deep brain stimulation in the treatment of movement disorders. J Neurosurg
2007;106:6215.
settings. Common stimulation-related side effects may include paresthesias due to

spread of current to lemniscal and sensory regions and muscle tightening due to
spread of current to motor fibers (corticobulbar and corticospinal tracts). More significant side effects may include dysarthria, cognitive deficits (particularly declines in
verbal fluency), and alterations in mood (including depression, anxiety, mania, and suicidality). The STN in particular may have a high risk for cognitive and mood side
effects, including executive dysfunction, hypomania (up to 15% in some series),
depression, anxiety and suicidality.46 However, randomized comparative studies to
confirm these clinical findings remain to be published. Although DBS has been repeatedly demonstrated to improve QOL,47 there are often significant difficulties with social
adjustment following DBS, particularly with marital and professional life.48 This finding
stresses the importance of preoperative counseling and discussions regarding the
patients expectations of surgery. See Table 1 for a summary of DBS complications.
SPECIFIC MOVEMENT DISORDERS AND TARGETS

Parkinsons Disease
Successful patient outcomes in PD have been obtained with DBS directed toward 1 of
3 intracranial targets, namely, STN, GPi, and VIM. There is currently no consensus on
which targets may be preferable for which symptoms; however, some important
insights have emerged from the literature. We anticipate that further data will demonstrate differences in particular symptom efficacy and side effect profiles (mood, motor,
cognitive, and QOL) so that the choice of an appropriate DBS target can be tailored to
an individual. There is currently good evidence to show that VIM DBS is effective in the
treatment of arm tremor but does not ameliorate other PD symptoms or capture leg
tremor in many cases.49 VIM DBS is generally not considered a first-line target in
PD; however, elderly patients with symptoms mostly linked to medication refractory
upper-extremity tremor who have impaired QOL or activities of daily living (ADLs)
may obtain excellent results.50 STN or GPi DBS may address tremor, bradykinesia,
and rigidity but have less impact on gait and postural instability, with much of the
outcome related to whether specific symptoms responded preoperatively to levodopa. DBS also does not prevent disease progression into areas such as gait, speech,
and cognition. Other DBS targets are currently under investigation in PD. Emerging
evidence has suggested that gait in PD may be improved by DBS directed to the pedunculopontine nucleus.51 However, proper outcome studies and criteria to determine patient selection have not been performed. Zona incerta DBS is another
potential target for tremor and other cardinal motor manifestations, and this remains
under investigation.52
Although the first randomized, double-blinded trials of STN versus GPi are currently
underway, there is preliminary evidence for the potential of differential responses and/
or side effects from the 2 targets based on clinical observation. In general, both procedures are well tolerated and considered generally safe in appropriately selected
patients, with meta-analyses showing comparable motor efficacy.53 There is some
evidence that STN DBS may be associated with a slightly greater motor/tremor
benefit; however, there may also be a higher risk of cognitive, behavioral, and mood
side effects.45 Although both STN and GPi improve dyskinesias and smooth on/off
fluctuations, there may be reasons to favor a specific target site, as well as reasons
to perform unilateral versus bilateral operations and to consider simultaneous versus
staged bilateral procedures. These differences will potentially emerge as randomized
studies are published. For example, STN DBS achieves dyskinesia reduction by
reducing levodopa requirements, whereas GPi DBS has a direct antidyskinetic effect,
651
652
Kluger et al
Table 3
Summary of VIM thalamic DBS outcomes for ET
Study
Sample Size
Study Type
Tremor Improvement
Nonmotor Outcomes
Pahwa et al., 2006160
26
Prosp NC
46% (unilateral) and 78%

(bilateral) FTM TRS
35%50% improvement on ADLs

(from TRS), drawing and
pouring
Lee and Kondziolka, 2005161
18
Case series
75% improvement FTM TRS
64% improvement in handwriting
Putzke et al., 2005162
22
Case series
N/A
Putzke et al., 2004163
52
Case series
70% improvement in ADLs
Kumar et al., 2003164
Case series
62% improvement in FTM TRS
Tolerance to DBS developed in 2 of

5 patients
Bryant et al., 2003
165
16
Case series
34% FTM TRS
45% improvement ADLs
Fields et al., 2003166
35
Case series
56% FTM TRS improvement
Significant improvements in
mood, QOL, and several
cognitive outcomes
Rehncrona
et al., 2003167
19
Prosp NC
N/A
Hariz et al., 200259
27
Prosp NC
Significant improvements in
mood, QOL, and emotional
constraints domain of QOL
Koller et al., 2001168
49
Case series
24% of patients required at least 1

additional surgical procedure
Obwegeser et al., 2001169
31
Case series
6-point reduction in FTM TRS
N/A
Pahwa et al., 2001170
17
Case control
(vs thalamotomy)
Equivalent benefit with less

complications than
thalamotomy
Krauss et al., 2001171
42
Case series
57% excellent outcome, 36%

marked improvement
N/A
40
Prosp NC
51% reduction in FTM TRS
Significant improvements across

multiple domains of QOL,
anxiety, and cognitive function
except verbal fluency.
Limousin et al., 1999110
37
Prosp NC
55% reduction in FTM TRS
Significant improvement in ADLs
Case series
Kumar et al., 1999173
Case series

and global disability
38 (head
tremor)
Case series
Head tremor improved in 75% of

patients
N/A
Hariz et al., 1999175
36
Case series
Lyons et al., 1998176
22
Case series
57% improvement on tremor ADL

scale
Ondo et al., 1998177
14
Case series
>50% improvement in ADLs and

disability scores
29
Prosp NC
> 50% improvement in FTM TRS
Hubble et al., 1996179
10
Prosp NC
>50% improvement in both

patient and clinician FTM TRS
ratings
63% improvement in patient and

clinician ratings of global
disability
Blond et al., 1992180
Case series
Sustained improvement in 75% of

patients
No change in MMSE, verbal

fluency, or Wisconsin Card Sort
Pahwa et al., 1999
172
Abbreviations: ADLs, activities of daily living; FTM TRS, Fahn Tolosa Marin tremor rating scale; MMSE, Folstein mini mental status examination; QOL, Quality of life.
Troster et al., 199957
653
654
Author
Type of Dystonia
Target
Follow-up
Period (mos)
Scale
Preoperative
Score
Postoperative
Score
Improvement (%)
Comments
Vercueil et al.,
2001181
Primary
generalized
GPi
12
BFMDRS (m/d)
N/A
N/A
67/81
Includes 12
patients with
thalamic DBS
alone and 3
with thalamic
and GPi DBS.
GPi
BFMDRS (m/d)
N/A
N/A
70/50
1
1
1
Primary
generalized
Primary DYT11
Primary DYT1
Cranial-cervical
GPi
GPi
GPi
12
24
6
BFMDRS (m/d)
BFMDRS (m/d)
BFMDRS (m/d)
N/A
N/A
N/A
N/A
N/A
N/A
86/86
41/43
66/66
Bereznai et al.,
2002182
3
1
Segmental
Primary DYT11
GPi
GPi
312
312
BFMDRS (m)
Tsui scale
N/A
N/A
N/A
N/A
72.50
45
Krauss et al.,
2002183
Cervical
GPi
20
TWSTRS
(s/d/p)
20.5/40.
5/6
7.5/12.7/3
62/69/50
Cif et al.,
2003184
15 Primary DYTI1
17 Primary DYT1
GPi
GPi
2436
2436
BFMDRS (m/d)
BFMDRS (m/d)
60.8/16.7
56.5/16.4
14.2/5.7
15.1/9.5
71/63
74/49
Katayama et al.,
2003185
Primary
GPi
BFMDRS (m)
1862
423
5192
Krauss et al.,
2003186
Primary DYT1
GPi
24
BFMDRS (m)
81
21.5
73
Kupsch et al.,
2003187
1
3
1
Primary DYT11
Primary DYT1
Segmental
GPi
GPi
GPi
312
312
312
BFMDRS (m)
BFMDRS (m)
BFMDRS (m)
34.5
40
32
27
20
19
22
50%
41
Includes 1
patient with
bilateral
pallidotomy
and 1 patient
with unilateral
pallidotomy
Kluger et al
Table 4
Summary of GPi DBS outcomes for dystonia
Yianni et al.,
2003188
12
Generalized
GPi
4184
BFMDRS (m)
79.7
45.3
46
Includes the
same patients
as the other
study by
Yianni and
colleagues,
2003
Cervical
GPi
212
TWSTRS (t)
57.8
23
59
2
11
7
Primary DYT11
Primary DYT1
Cervical
GPi
GPi
GPi
12
12
12
BFMDRS (m)
BFMDRS (m)
TWSTRS (s/d/p)
N/A
N/A
21.3/21.7/
15.1
N/A
N/A
10/14/8.3
85
46
50/38/43
Cif et al.,
2004190
Myoclonusdystonia
syndrome
GPi
20
UMRS
69
13
81
BFMDRS (m/d)
9.5/9
1.5/1
84/89
Coubes et al.,
2004191
17
14
Primary DYT11
Primary DYT1
GPi
GPi
24
24
BFMDRS (m)
BFMDRS (m)
62.6
56.3
12.4
13.4
83
75
Detante et al.,
2004192
13
3
Primary generalized
Secondary PKAN
STN
STN
3
3
N/A
N/A
N/A
N/A
N/A
N/A
No improvement
No improvement
Eltahawy et al.,
200433
Primary DYT11
GPi
BFMDRS (m)
88
66
25
1
3
Primary DYT1
Cervical
GPi
GPi
6
6
BFMDRS (m)
TWSTRS (t)
48
37.7
16
16
21
57
Krause et al.,
2004193
4
6
1
Primary DYT11
Primary DYT1
Cervical
GPi
GPi
GPi
1266
1266
1266
BFMDRS (m)
BFMDRS (m)
BFMDRS (m)
72
73.9
6
34
50
6
53
32
0
Trottenberg et al.,
2005194
Secondary
tardive
GPi
BFMDRS (m/d)
32/8
N/A
87/96
Vayssiere et al.,
2004195
19
Primary
generalized
GPi
N/A
BFMDRS
N/A
N/A
>80
Study also
includes
pallidotomy
patients
7
Yianni et al.,
2003189
655
656
Kluger et al
Table 4
(continued)
Author
Type of Dystonia
Target
Follow-up
Period (mos)
Scale
Preoperative
Score
Postoperative
Score
Improvement (%)
Comments
Bittar et al.,
2005196
Primary DYT11
GPi
24
BFMDRS (t)
103.8
55.8
46
DYT11 and
DYT1
analyzed
together
4
6
Primary DYT1
Cervical
GPi
GPi
24
24
TWSTRS (t)
57.8
23.7
59
Castelnau et al.,
2005197
Secondary PKAN
GPi
21
BFMDRS (m/d)
75/20
20/9.6
74/53
Chou et al.,
2005198
Cervical dystonia
and ET
STN
TWSTRS (s/d)
14/20
3/0
79/100
Vidailhet,
200560
7
1
Primary DYT11
Primary DYT1
GPi
GPi
12
12
BFMDRS (m/d)
BFMDRS (m/d)
55.1/14.7
41.96/10.2
26.1/8.5
18.7/5.5
53/46
55.4/45
Zorzi et al.,
2005199
1
8
Primary DYT11
Primary DYT1
GPi
GPi
4
19
BFMDRS (m/d)
BFMDRS (m/d)
47/11
68.9/17.9
14/6
46.5/12.6
70/45
32/37
Diamond et al.,
2006200
Primary DYT11
GPi
UDRS
44.6
27.5
38
All groups
analyzed
together. 2
patients with
pallidotomy
5
1
Primary DYT1
Hemidystonia
GPi
GPi
5
3
Primary DYT11
GPi
BFMDRS (m/d)
36.4/10
20.2/5.9
45/41
All groups
analyzed
together
27
7
Primary DYT1
Primary
GPi
GPi
6
6
Kupsch et al.,
200663
Class 1 evidence
Starr et al.,
2006201
6
3
1
1
1
1
4
2
Zhang et al.,
2006202
GPi
GPi
GPi
GPi
GPi
13
22
9
12
33
BFMDRS
BFMDRS
BFMDRS
BFMDRS
BFMDRS
GPi
32
GPi
(m)
(m)
(m)
(m)
(m)
59.6
22.6
30
30
82
24.2
12
3
6
51
59
47
90
80
38
BFMDRS (m)
54
49.5
No improvement
20
BFMDRS (m)
46.5
24.6
47
11
BFMDRS (m)
83
72.8
12
Secondary tardive
dystonia
STN
BFMDRS (m)
98.8
92
STN
BFMDRS (m)
26.5
91
STN
BFMDRS (m)
76
91
Secondary
antiemetics
Secondary
neonatal
anoxia
Other secondary
STN
N/A
N/A
N/A
N/A
Did poorly
12
Primary DYT11
GPi
12
BFMDRS (m/d)
35/8
4/2
89/75
Primary DYT1
GPi
12
6 cases bilateral
STN, 2 cases
unilateral STN,
1 case left STN
and right GPi
DYT1 1 and
DYT1 analyzed
together
GPi
Alterman,
2007203
Primary DYT11
Segmental
Cranial-cervical (MS)
Secondary PKAN
Secondary
cerebral palsy
Secondary
posttraumatic
Secondary
tardive
Generalized
657
658
Follow-up
Target Period (mos) Scale
Preoperative
Score
Postoperative
Score
Improvement (%) Comments
10 Secondary tardive
GPi
ESRS
73.1
27.8
AIMS
25
31.1
Evidente et al.,
2007205
X-linked
dystonia
Parkinsonism
GPi
12
UPDRS-III
21
62
BFMDRS (t)
32.5
9.5
72
Grips et al.,
2007206
Segmental
GPi
N/A
UDRS
36.9
16.1
56
BFMDRS
GDS
25.6
29.3
13.1
10.3
61
67
All patients
previously
reported
Author
Damier et al.,
2007204
Type of Dystonia
GPi
GPi
62
50%
improvement
with doubleblind
evaluation
24
Hung et al.,
200762
10 Cervical
GPi
1267
TWSTRS (s/d/p) 21.9/18/11.7
9.9/7.4/5.8
55/52/51
Kiss et al.,
2007207
10 Cervical
GPi
12
TWSTRS (s/d/p) 14.7/14.9/26.6 8.4/5.4/9.2
43/64/65
Class 1 evidence
Kleiner-Flisman
et al., 2007208
Cervical
STN
12
1
1
Cervical
Cervical
STN
STN
12
12
Primary
generalized
STN
12
BFMDRS (m/d)
TWSTRS (s/d/p)
TWSTRS (s/d/p)
BFMDRS (m/d)
TWSTRS (s/d/p)
BFMDRS (m/d)
36.5/5
31/27/14
21/16/17
53/14
26/27/15.3
23/5
29/10
23/20/5.5
12/5/14.3
59/17
28/24/18.3
12/3
21/50
26/26/61
43/69/16
11/-21
8/11/ 20
72/40
Primary
generalized
STN
29
BFMDRS (m/d)
N/A
N/A
23/42
Novak et al.,
2007209
Kluger et al
Table 4
(continued)
Ostrem et al.,
200767
Cranial-cervical
Sun et al.,
200766
12 Primary
generalized
2
Secondary tardive
Tisch et al.,
2007210
7
8
Primary DYT1
GPi
Vidailhet et al.,
2007211
Primary DYT11
GPi
36
Loher et al.,
2008212
4
2
Primary DYT11
15 Primary DYT1
GPi
GPi
6
6
BFMDRS (m/d)
TWSTRS (t)
22/6
39
6.1/3.7
17
72/38
54
STN
642
BFMDRS
N/A
N/A
76100
Groups reported
together
STN
642
GPi
BFMDRS (m/d)
38.9/9.0
11.9/4.1
70/58
DYT1 1 and DYT1 analyzed together
BFMDRS (m/d)
46.3/11.6
19.3/6.3
58/46
DYT11 and DYT1

analyzed
together
36
36
36
TWSTRS (s/d/p) 20.5/40.5/6

BFMDRS (m/d) 81/18.5
14.7/15.7/3.7
28.3/7.5
28/61/38
65/59
Magarinos-Ascone 10 Primary generalized GPi

et al., 200864
12
BFMDRS (m/d)
57.8/18.1
20.0/8.6
65/52
Sako et al.,
2008213
21
BFMDRS (m/d)
N/A
N/A
86/80
Secondary tardive
GPi
1 patient DYT11
This table is an expanded version of that published in the work of Ostrem, 2007, with full permission from Elsevier Ltd.
Abbreviations: BFMDRS (m/d), Burke-Fahn-Marsden dystonia rating scale (motor subscore, maximum 120/disability subscore, maximum 30); BFMDRS (t), BurkeFahn-Marsden dystonia rating scale, total score; PKAN, pantothenate kinase associated neurodegeneration; TWSTRS (s/d/p), Toronto western spasmotic torticolis
rating scale (severity, maximum 35/disability, maximum 30/pain, maximum 18); UDRS, Unified dystonia rating scale; UPDRS-III, Unified Parkinson disease rating
scale, motor subscore (maximum 108); UMRS, Unified myoclonus rating scale; ESRS, Extrapyramidal symptoms rating scale; AIMS, Abnormal involuntary movements scale; GDS, Global dystonia scale; Primary generalized, Primary generalized dystonia of an unknown etiology; Primary DYT1 1, Primary generalized
DYT1 gene positive dystonia; Primary DYT1 -, Primary; generalized DYT1 gene negative dystonia, Percentage of change was calculated as [(PreoperativePostoperative)/Preoperative]x100. For generalized and cervical dystonia, only reports with 5 or more cases were included. For other types of dystonia all published reports
were included.
GPi
Cervical
GPi
Primary generalized GPi
659
660
Study
Sample
Size
Study Type
Dx
Target
Motor Improvement
Nonmotor Outcomes
Welter et al.,
2008214
Randomized,
controlled,
doubleblinded,
crossover
TS
GPiCM-Pf
78% and 45% reductions

in Yale tic severity scale
with GPi and CM-pf
respectively. No further
improvement with
both targets
No change in neuropsychological
testing. Mild improvements in
impulsivity and depression were
noted with CM-pf only
Dehning et al.,
200875
Case study
TS
GPi
88% improvement in
YGTSS
No change in neuropsychological
testing
Shields et al.,
200876
Case study
TS
Anterior IC
and CM-Pf
23% improvement in
YGTSS with IC; 46%
improvement with CM
Depression with AIC
Servello et al.,
200874
18
Prosp NC
TS
CM-Pf
Improvements in
YGTSS not quantified
Improvements reported in
psychiatric comorbidities.
Neuropsychology testing
performed but results not
reported
Bajwa et al.,
2007215
Case study
TS
CM
66% improvement in
YGTSS
OCD symptoms also improved
Kuhn et al.,
200777
Case study
TS
NAc
41% improvement in
YGTSS
OCD symptoms also improved
Shahed et al.,
2007216
Case study
TS
GPi
84% improvement in
YGTSS
Improved OCD symptoms and

QOL. Neuropsychology tests
stable or improved, except mild
decrease in memory
Maciunas et al.,
2007217
Randomized,
controlled,
doubleblind,
crossover
TS
CM-Pf
44% improvement
in YGTSS
Trend toward decreased

neuropsychology and improved
mood. QOL significantly
improved
Kluger et al
Table 5
Summary of DBS outcomes for other movement disorders
Case study
TS
One patient GPi,

other CM
85%90% reduction
in tics/minute both
patients
Improved OCD symptoms
Flaherty et al.,
2005219
Case study
TS
Anterior IC
25% improvement
in YGTSS
Euthymic with optimal settings
Diederich et al.,
2005220
Case study
TS
GPi
46% improvement
in YGTSS
Depression and anxiety mildly

improved. Neuropsychology
stable
Houeto et al.,
2005221
Case study
TS
CM-Pf and GPi
65% improvement
in YGTSS with either
or both sites
Neuropsychology stable or
improved Mild improvements
with depression and impulsivity
with CM-Pf
VisserVandewalle
et al., 2003222
Case series
TS
CM
82% reduction
tics/minute
Mild decrease in 1 patient on

timed neuropsychology tests
Vandewalle et al.,
1999223
Case study
TS
CM
901% reduction
tics/ minute
N/A
Fasano et al.,
200897
Case study
HD
GPi
Complete resolution
of chorea
Continued deterioration of
cognition and gait
Hebb et al.,
200698
Case study
HD
GPi
Significant improvement
in total UPDRS and
chorea
Noted weight gain and stable

neuropsychology function over
12 mo
Moro et al.,
2004224
Case study
HD
GPi
44% and 37% improvements

in chorea and
dystonia
Mild improvements in functional

assessment and independence
Freund et al.,
200799
Case study
SCA-2
VIM STN
Improved tremor
Improved speech and ADLs
Shimojima et al.,
2005100
Case study
SCA (negative
genetic
testing)
VIM
45% improvement in
FTM TRS
Improved ADLs
Foote and Okun,

200596
Case study
Traumatic
Holmes
tremor
VIM, VOA
and VOP
40% improvement in
FTM TRS
Significant improvement in
disability
Ackermans et al.,
2006218
661
662
Sample
Size
Study Type
Dx
Target
Motor Improvement
Nonmotor Outcomes
Nikkhah et al.,
200469
Case series
Holmes tremor
VIM
Improved tremor and

dystonia
Improved speech
Kudo et al.,
2001225
Case study
Holmes tremor
VIM
Improved tremor
N/A
Plaha et al.,
200892
13
Case series
PD, MS, ET,

Holmes,
dystonic
tremor
Zona Incerta
60%90% improvement
in all tremors
N/A
Lim et al.,
200779
Case studies
MS and stroke
VIM/VOA and
GPi (stroke
only)
40% improvement in
MS with VIM/VOA, 7%
in stroke with GPi only
Mild improvements in ADL

ratings for both patients
Foote et al.,
200685
Case series
MS 1 Trauma 3
VIM VOA/VOP
23%66% improvement
in TRS, trend toward
more improvement with
dual leads in 2 patients
N/A
Moringlane et al.,
200490
Case study
MS
VL
Improved tremor
No change in neuropsychology
function, improved ADLs
Wishart et al.,
200395
Case series
MS
VIM
Improved tremor
Dysarthria in 1 patient
Schulder et al.,
200393
Case series
MS
VIM
68% improvement in
Bain-Finchley TRS
Stimulation-related fatigue in
1 patient
Bittar et al.,
200583
10
Case series
MS
VOP/ZI
64% and 36%

improvement of
postural and intention
tremor on 10-point
scale
N/A
Berk et al.,
200282
12
Case series
MS
VIM
Overall tremor reduction

63% on Fahn rating
scale
Improved ADLs. No change in

SF-36 QOL
Study
Kluger et al
Table 5
(continued)
Case series
MS
VIM
61% tremor reduction

Bain-Finchley scale
Mild neuropsychology decline

over 30 mo, possibly 2/2 disease
progression
Hooper et al.,
200287
10
Prospective
MS
Thalamic
(targeted
to tremor)
Significant reduction
on Fahn-TRS
No change in neuropsychology
Mild improvement in anxiety
Matsumoto
et al., 200188
Case series
MS
VIM
Significant reduction
in clinical TRS
No change in disability, mild

decrease in QOL
Schuurman
et al., 200094
Randomized
(vs
thalamotomy)
MS
VIM
Improvement on UPDRS
tremor rating
N/A
Brice and
McLellan,
198084
Case series
MS
Thalamus
Improved tremor
Dysarthria
Montgomery
et al., 199989
15
Case series
MS
VIM
Improved clinical
TRS
N/A
Benabid et al.,
199681
Case series
MS
VIM
Tremor improved in
2 patients
N/A
Geny et al.,
199686
13
Case series
MS
VIM
Significant decrease in
tremor in 9 patients
Improvement in functional
disability
Nguyen and Degos,

199391
Case series
MS, germinoma,
TBI and
mercury
poisoning
VIM
Tremor improved from

severe to mild or
none in all subjects
Improved functional use

of arm
Siegfried and Lippitz,

199480
11
Case series
MS (9), trauma,
stroke
VIM
70%100% of patients
with tremor control (not
reported by subgroup)
Tremor control limited in some

patients by side effects, mainly
dysarthria
Abbreviations: ADLs, activities of daily living; AIC, anterior internal capsule; CM-Pf, centromedian parafasicular, Dx, diagnosis; ET, essential tremor; FTM TRS, Fahn
Tolosa Marin tremor rating scale; HD, Huntingtons disease; IC, Internal capsule; MS, multiple sclerosis; NAc, nucleus accumbens; OCD, obsessive compulsive
disorder; PD, Parkinsons disease; QOL, Quality of life; SCA, spinocerebellar ataxia; SF-36, 36-item short-form health survey; TBI, traumatic brain injury TS, Tourette
syndrome; VL, ventral lateral; YGTSS, Yale Global Tic Severity Scale.
Data from Ostrem J, Marks WJ, Volz M, et al. Pallidal deep brain stimulation in patients with cranial-cervical dystonia (Meige syndrome). Mov Disord
2007;22(13):1885; with permission.
Schulder et al.,
200393
663
664
Kluger et al
and this may provide a rationale for target choice in an individual patient.54 A summary
of published studies for DBS for PD is provided in Table 2.
Essential Tremor
VIM thalamic DBS has proven to be a generally well-tolerated and efficacious treatment for ET.55 Candidates for ET DBS usually have postural and/or action tremors,
which significantly interfere with ADLs and QOL and should be medication refractory,
including maximally tolerated doses of primidone (and/or other anticonvulsants),
propanolol (and/or other beta blockers), and a benzodiazepine (typically clonazepam).
VIM DBS has been particularly efficacious for contralateral limb tremor, although it has
some ipsilateral positive effects.56 VIM DBS may improve vocal or head tremor, but, in
our experience, it is not a reliable benefit when looking across patients. Botulinum
toxin injections may be synergistic with DBS for these tremors, particularly if there
is a dystonic component. Potential chronic side effects of VIM DBS include speech
abnormalities (dysarthria and decreased verbal fluency) and difficulty with gait, particularly with bilateral stimulator placement, and if there are premorbid issues such as
cerebrovascular disease or ventricular enlargement. Possibly with the exception of
verbal fluency, cognitive and mood outcomes do not seem to decline with VIM DBS
in the ET population.57 However, given recent data of neuropsychological impairments
in ET and reports of mood disturbances and suicides following VIM DBS, careful
screening is still appropriate.58 In Table 3 we provide a complete review of the literature on VIM DBS outcomes for motor, mood, QOL, and cognitive outcomes.59
Dystonia
Bilateral GPi DBS has been recently demonstrated by several groups as safe and efficacious in the treatment of primary generalized dystonias,60 tardive dystonia,61 and in
some cases of focal or segmental dystonia.62,63 There have also been several case
reports of successful treatment of myoclonus-dystonia syndrome with bilateral GPi
DBS64 and thalamic DBS.65 Although not commonly used, STN and thalamic DBS
have shown efficacy in primary, tardive, and segmental dystonia.66 In patients with
nontardive secondary hemidystonia, segmental, or focal dystonia, the appropriate
target(s) are not clear at this time.
Patient selection follows similar principles to PD. Patients should have a definitive
diagnosis of dystonia by a movement disorder neurologist/neurologist experienced
in dystonia and have significant effects on QOL or ADLs despite maximally tolerated
medical treatments, including anticholinergics, benzodiazepines, muscle relaxants,
and antiepileptics. In patients with focal or limited segmental dystonia, an adequate
trial of botulinum toxin injections should also be attempted. Mobile dystonia has
been found to be more responsive to DBS regardless of the underlying etiology,
and fixed orthopedic deformities are unlikely to be improved by DBS.
In Table 4 we provide a review of the literature on GPi dystonia DBS outcomes. The
majority of studies of DBS in dystonia have been performed in primary generalized
dystonia, where patients have generally shown a 40%60% improvement in dystonia
severity. Similar results have been obtained in cervical dystonia,62 Meige syndrome67
and tardive dystonia.61 Case reports of improvement in dystonia following GPi DBS
have also been reported in dystonia secondary to trauma, stroke, and pantothenate
kinase deficiency.6870 DBS for dystonia is notably different from other disorders in
that DBS typically has a delayed benefit possibly owing to cortical remodeling due
to stimulation effects, although the exact cause of this finding is currently unknown.71
Similarly, following DBS, dystonic patients may experience lasting benefits after
discontinuation of DBS therapy. Dystonia patients may also accumulate benefit over
several months or even longer, suggesting that GPi DBS in dystonia may have both
direct effects from stimulation and also induce longer-term neuroplastic changes or
disease-modifying benefits.23
The potential chronic side effects of GPi DBS for dystonia are similar to those seen
in PD. With regard to mood disturbances, a careful neuropsychiatric evaluation,
particularly in patients with tardive dystonia, is strongly recommended.58 Patients
with dystonia appear to have a lower risk of cognitive side effects after GPi DBS,
possibly because they are younger and the underlying disease may be associated
with less cognitive dysfunction and fewer comorbidities.72 However, suicides in
patients, particularly those with premorbid depression, have been reported following
GPi DBS for dystonia.73 Another side effect noted in a small case series of patients
with Meige syndrome was the development of a subjective sense of clumsiness and
slowness in previously unaffected body parts.67 Although these symptoms were often
not evident on examination, they were persistent and present only when DBS was
turned on. Side effects from field spread into pallidal and surrounding regions are
similar to what is seen in GPi DBS for PD.
OTHER MOVEMENT DISORDERS
There have been several case series demonstrating the potential for DBS in Tourette
syndrome (TS). These case series have used multiple separate targets and combinations of targets, including the centromedian thalamus-parafascicular complex
(including the ventralis oralis complex of the thalamus),74 GPi,75 the anterior limb of
the internal capsule,76 and the nucleus accumbens.77 As a side benefit, many of these
patients also noted improvements in comorbid psychiatric symptoms, including anxiety
and obsessive-compulsive disorder. Principles of patient selection are similar to those
in other movement disorders, namely, the use of a multidisciplinary team to carefully
screen patients and failure to achieve adequate symptom control despite maximal
medical management. The Tourette Syndrome Association has now published general
guidelines for Tourette DBS.78 There are several small case series showing improvement in poststroke tremor,79,80 posttraumatic tremor,79,80 and multiple sclerosis (MS)
tremor with DBS.7995 These treatments typically target the VIM, although some authors
have used multiple simultaneous thalamic or GPi and thalamic targets.79,85,96 VIM in
complex tremors may not be the target of choice, and other areas of thalamus will
need to be explored ventralis oralis anterior, ventralis oralis posterior and centromedian
(Voa, Vop, CM). In these patients, one must be careful to determine how much disability
is due to tremor, which may improve with DBS, versus ataxia or weakness, which will not
improve with DBS. Three case reports suggest that chorea in Huntingtons disease (HD)
may be reduced with bilateral GPi DBS.97,98 Case reports of efficacy in some of the
spinal cerebellar ataxias have also been reported.99,100 In Table 5 we provide a review
of the literature on DBS outcomes in other movement disorders for motor, mood, QOL,
and cognitive outcomes. In studies of mixed populations, we included only studies
where specific outcome information was available for each diagnosis.
SUMMARY
DBS is an efficacious treatment option for appropriately selected patients with PD, ET,
and dystonia. Indications and options for DBS continue to expand rapidly. There are
important side effects and benefits that may influence target selection for individual
patients. Advances in our understanding of the pathophysiology of movement disorders combined with technological advances in our ability to precisely target neuroanatomical structures continue to push improvements in the efficacy and safety of DBS
665
666
Kluger et al
for basal ganglia disorders. Basic science advances need to be combined with welldesigned clinical trials to define rational treatment algorithms to improve motor, mood,
cognitive, and QOL outcomes.
ACKNOWLEDGMENT
The authors would also like to acknowledge Leah Gaspari for her assistance in the
preparation of this manuscript.
REFERENCES
1. Horsley V. The functions of the so-called motor areas of the brain. BMJ 1909;124:
528.
2. Putnam T. Relief from unilateral paralysis agitans by section of the lateral pyramidal tract. Arch Neurol Psychiatry 1938;40:1049.
3. Walker A. Cerebral pedunculotomy for the relief of involuntary movements. II.
Parkinsonian tremor. J Nerv Ment Dis 1952;116(6):76675.
4. Spiegel E, Wycis H, Marks M, et al. Stereotaxic apparatus for operations on the
human brain. Science 1946;106:34950.
5. Cooper I. Surgical alleviation of parkinsonism: effects of occlusion of the anterior
choroidal artery. J Am Geriatr Soc 1954;11:691718.
6. Hassler R. The influence of stimulations and coagulations in the human thalamus
on the tremor at rest and its physiopathologic mechanism. In: Greenfield,
Godwin J, Russell D, editors. Proceedings of the Second International Congress
of Neuropathology. London. Amsterdam: Excerpta Medica; 1955. p. 63742.
7. Svennilson E, Torvik A, Lowe R, et al. Treatment of parkinsonism by stereotactic
thermolesions in the pallidal region. A clinical evaluation of 81 cases. Acta
Psychiatr Scand 1960;35:35877.
8. Andy O, Jurko M, Sias F. Subthalamotomy in treatment of parkinsonian tremor.
J Neurosurg 1963;20:86070.
9. Fager C. Evaluation of thalamic and subthalamic surgical lesions in the alleviation of Parkinsons disease. J Neurosurg 1968;28:1459.
10. Cotzias G, Woert MV, Schiffer L. Aromatic amino acids and modification of
parkinsonism. N Engl J Med 1967;276(7):3749.
11. Tasker R, Siqueira J, Hawrylyshyn P, et al. What happened to VIM thalamotomy
for Parkinsons disease? Appl Neurophysiol 1983;46(14):6883.
12. Laitinen L, Bergenheim A, Hariz M. Ventroposterolateral pallidotomy can abolish
all parkinsonian symptoms. Stereotact Funct Neurosurg 1992;58(14):1421.
13. Gill S, Heywood P. Bilateral dorsolateral subthalamotomy for advanced Parkinsons disease. N Engl J Med 1997;337:103642.
14. Alexander G, Crutcher M, DeLong M. Basal ganglia-thalamocortical circuits:
parallel substrates for motor, oculomotor, prefrontal and limbic functions.
Prog Brain Res 1990;85:11946.
15. DeLong M. Primate models of movement disorders of basal ganglia origin.
Trends Neurosci 1990;13(7):2815.
16. Benabid A, Pollak P, Louveau A, et al. Combined (thalamotomy and stimulation)
stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease.
Appl Neurophysiol 1987;50(16):3446.
17. Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci 1989;12(10):36675.
18. Hooper A, Okun M, Foote K, et al. Clinical cases where lesion therapy was chosen
over deep brain stimulation. Stereotact Funct Neurosurg 2008;86(3):14752.
19. Wichmann T, DeLong M. Basal ganglia discharge abnormalities in Parkinsons

disease. J Neural Transm Suppl 2006;70:215.
20. Lozano A, Carella F. Physiologic studies in the human brain in movement disorders. Parkinsonism Relat Disord 2002;8(6):4558.
21. Grill W, Snyder A, Miocinovic S. Deep brain stimulation creates an informational
lesion of the stimulated nucleus. Neuroreport 2004;15(7):113740.
22. Meissner W, Leblois A, Hansel D, et al. Subthalamic high frequency stimulation
resets subthalamic firing and reduces abnormal oscillations. Brain 2005;128
(Pt 10):237282.
23. Johnson M, Miocinovic S, McIntyre C, et al. Mechanisms and targets of
deep brain stimulation in movement disorders. Neurotherapeutics 2008;
5(2):294308.
24. Benazzouz A, Piallat B, Pollak P, et al. Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: electrophysiological data. Neurosci Lett 1995;189:7780.
25. Miocinovic S, Parent M, Butson C, et al. Computational analysis of subthalamic
nucleus and lenticular fasciculus activation during therapeutic deep brain stimulation. J Neurophysiol 2006;96(3):156980.
26. McIntyre C, Savasta M, Walter B, et al. How does deep brain stimulation work?
Present understanding and future questions. J Clin Neurophysiol 2004;21(1):
4050.
27. Shen K, Zhu Z, Munhall A, et al. Synaptic plasticity in rat subthalamic nucleus
induced by high-frequency stimulation. Synapse 2003;50(4):3149.
28. Temel Y, Visser-Vandewalle V, Kaplan S, et al. Protection of nigral cell death by
bilateral subthalamic nucleus stimulation. Brain Res 2006;1120(1):1005.
29. Hammond C, Ammari R, Bioulac B, et al. Latest view on the mechanism of action
of deep brain stimulation. Mov Disord 2008;23:211121.
30. Vitek J, Hashimoto T, Peoples J, et al. Acute stimulation in the external segment
of the globus pallidus improves parkinsonian motor signs. Mov Disord 2004;
19(8):90715.
31. Kuncel A, Cooper S, Wolgamuth B, et al. Clinical response to varying the stimulus parameters in deep brain stimulation for essential tremor. Mov Disord 2006;
21(11):19208.
32. Okun M, Fernandez H, Pedraza O, et al. Development and initial validation of
a screening tool for Parkinson disease surgical candidates. Neurology 2004;
63(1):1613.
33. Eltahawy H, Saint-Cyr J, Giladi N, et al. Primary dystonia is more responsive than
secondary dystonia to pallidal interventions: outcome after pallidotomy or pallidal deep brain stimulation. Neurosurgery 2004;54(3):6139.
34. Pretto T, Dalvi A, Kang U, et al. A prospective blinded evaluation of deep brain
stimulation for the treatment of secondary dystonia and primary torticollis
syndromes. J Neurosurg 2008;109(3):4059.
R, et al. Core assessment program for surgical interven35. Defer G, Widner H, Marie
tional therapies in Parkinsons disease (CAPSIT-PD). Mov Disord 1999;14(4):57284.
36. Haq I, Foote K, Okun M. Is earlier better? What do we really mean when we
advocate for early DBS in Parkinson disease? Pract Neurol 2008;4:2431.
37. Rodriguez R, Fernandez H, Haq I, et al. Pearls in patient selection for deep brain
stimulation. Neurologist 2007;13(5):25360.
38. Okun M, Tagliati M, Pourfar M, et al. Management of referred deep brain stimulation failures: a retrospective analysis from 2 movement disorders centers. Arch
Neurol 2005;62(8):12505.
667
668
Kluger et al
39. Sudhyadhom A, Bova F, Foote K, et al. Limbic, associative, and motor territories
within the targets for deep brain stimulation: potential clinical implications. Curr
Neurol Neurosci Rep 2007;7(4):27889.
40. Gorgulho A, Salles AD, Frighetto L, et al. Incidence of hemorrhage associated
with electrophysiological studies performed using macroelectrodes and microelectrodes in functional neurosurgery. J Neurosurg 2005;102(5):88896.
41. Hariz M. Safety and risk of microelectrode recording in surgery for movement
disorders. Stereotact Funct Neurosurg 2002;78(34):14657.
42. Kenney C, Simpson R, Hunter C, et al. Short-term and long-term safety of deep
brain stimulation in the treatment of movement disorders. J Neurosurg 2007;
106(4):6215.
43. Hariz M, Rehncrona S, Quinn N, et al. Multicenter study on deep brain stimulation in Parkinsons disease: an independent assessment of reported adverse
events at 4 years. Mov Disord 2008;23(3):41621.
44. Lang A, Houeto J, Krack P, et al. Deep brain stimulation: preoperative issues.
Mov Disord 2006;21(Suppl 14):S17196.
45. Mehdorn H, Goebel S, Falk D, et al. Deep brain stimulation for movement disorders
and its neuropsychological implications. Acta Neurochir Suppl 2008;101:912.
46. Smeding H, Speelman J, Koning-Haanstra M, et al. Neuropsychological effects
of bilateral STN stimulation in Parkinson disease: a controlled study. Neurology
2006;66(12):18306.
47. Diamond A, Jankovic J. The effect of deep brain stimulation on quality of life in
movement disorders. J Neurol Neurosurg Psychiatry 2005;76(9):118893.
48. Schupbach M, Gargiulo M, Welter M, et al. Neurosurgery in Parkinson disease:
a distressed mind in a repaired body? Neurology 2006;66(12):18116.
49. Fraix V, Pollak P, Moro E, et al. Subthalamic nucleus stimulation in tremor dominant parkinsonian patients with previous thalamic surgery. J Neurol Neurosurg
Psychiatry 2005;76(2):2468.
50. Hariz M, Alesch PKF, Augustinsson L, et al. Multicentre European study of
thalamic stimulation for parkinsonian tremor: a 6 year follow-up. J Neurol Neurosurg Psychiatry 2008;79(6):6949.
51. Stefani A, Lozano A, Peppe A, et al. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinsons disease. Brain
2007;130(Pt 6):1596607.
52. Plaha P, Ben-Shlomo Y, Patel N, et al. Stimulation of the caudal zona incerta is
superior to stimulation of the subthalamic nucleus in improving contralateral
parkinsonism. Brain 2006;129(Pt 7):173247.
53. Weaver F, Follett K, Hur K, et al. Deep brain stimulation in Parkinson disease:
a metaanalysis of patient outcomes. J Neurosurg 2005;103(6):95667.
54. Guridi J, Obeso J, Rodriguez-Oroz M, et al. L-dopa-induced dyskinesia and
stereotactic surgery for Parkinsons disease. Neurosurgery 2008;62(2):3115.
55. Lyons K, Pahwa R. Deep brain stimulation and tremor. Neurotherapeutics 2008;
5(2):3318.
56. Ondo W, Vuong KD, Almaguer M, et al. Thalamic deep brain stimulation: effects
on the nontarget limbs. Mov Disord 2001;16(6):113742.
57. Troster A, Fields J, Pahwa R, et al. Neuropsychological and quality of life
outcome after thalamic stimulation for essential tremor. Neurology 1999;53(8):
177480.
58. Okun M, Rodriguez R, Mikos A, et al. Deep brain stimulation and the role of the
neuropsychologist. Clin Neuropsychol 2007;21(1):16289.
59. Hariz G, Lindberg M, Bergenheim A. Impact of thalamic deep brain stimulation

on disability and health-related quality of life in patients with essential tremor.
J Neurol Neurosurg Psychiatry 2002;72:4752.
60. Vidailhet M, Vercueil L, Houeto J, et al. Bilateral deep-brain stimulation of the
globus pallidus in primary generalized dystonia. N Engl J Med 2005;352(5):
45967.
61. Cohen O, Hassin-Baer S, Spiegelmann R. Deep brain stimulation of the internal
globus pallidus for refractory tardive dystonia. Parkinsonism Relat Disord 2007;
13(8):5414.
62. Hung S, Hamani C, Lozano A, et al. Long-term outcome of bilateral pallidal deep
brain stimulation for primary cervical dystonia. Neurology 2007;68(6):4579.
63. Kupsch A, Benecke R, Muller J, et al. Pallidal deep-brain stimulation in primary
generalized or segmental dystonia. N Engl J Med 2006;355(19):197890.
64. Magarinos-Ascone C, Regidor I, Martnez-Castrillo J, et al. Pallidal stimulation
relieves myoclonus-dystonia syndrome. J Neurol Neurosurg Psychiatry 2005;
76(7):98991.
65. Trottenberg T, Meissner W, Kabus C, et al. Neurostimulation of the ventral intermediate thalamic nucleus in inherited myoclonus-dystonia syndrome. Mov Disord 2001;16(4):76971.
66. Sun B, Chen S, Zhan S, et al. Subthalamic nucleus stimulation for primary dystonia and tardive dystonia. Acta Neurochir Suppl 2007;97(Pt 2):20714.
67. Ostrem J, Marks WJ, Volz M, et al. Pallidal deep brain stimulation in patients with
cranial-cervical dystonia (Meige syndrome). Mov Disord 2007;22(13):188591.
68. Loher T, Hasdemir M, Burgunder J, et al. Long-term follow-up study of chronic
globus pallidus internus stimulation for posttraumatic hemidystonia. J Neurosurg
2000;92(3):45760.
69. Nikkhah G, Prokop T, Hellwig B, et al. Deep brain stimulation of the nucleus ventralis intermedius for Holmes (rubral) tremor and associated dystonia caused by
upper brainstem lesions. Report of two cases. J Neurosurg 2004;100(6):107983.
70. Shields D, Sharma N, Gale J, et al. Pallidal stimulation for dystonia in pantothenate kinase-associated neurodegeneration. Pediatr Neurol 2007;37(6):4425.
71. Tisch S, Rothwell J, Limousin P, et al. The physiological effects of pallidal deep
brain stimulation in dystonia. IEEE Trans Neural Syst Rehabil Eng 2007;15(2):
16672.
72. Pillon B, Ardouin C, Dujardin K, et al. Preservation of cognitive function in dystonia treated by pallidal stimulation. Neurology 2006;66(10):15568.
73. Appleby B, Duggan P, Regenberg A, et al. Psychiatric and neuropsychiatric
adverse events associated with deep brain stimulation: a meta-analysis of ten
years experience. Mov Disord 2007;22(12):17228.
74. Servello D, Porta M, Sassi M, et al. Deep brain stimulation in 18 patients with
severe Gilles de la Tourette syndrome refractory to treatment: the surgery and
stimulation. J Neurol Neurosurg Psychiatry 2008;79(2):13642.
75. Dehning S, Mehrkens J, Muller N, et al. Therapy-refractory Tourette syndrome:
beneficial outcome with globus pallidus internus deep brain stimulation. Mov
Disord 2008;23(9):13002.
76. Shields D, Cheng M, Flaherty A, et al. Microelectrode-guided deep brain stimulation for Tourette syndrome: within-subject comparison of different stimulation
sites. Stereotact Funct Neurosurg 2008;86(2):8791.
77. Kuhn J, Lenartz D, Mai J, et al. Deep brain stimulation of the nucleus accumbens
and the internal capsule in therapeutically refractory Tourette-syndrome. J Neurol 2007;254(7):9635.
669
670
Kluger et al
78. Mink J, Walkup J, Frey K, et al. Patient selection and assessment recommendations
for deep brain stimulation in Tourette syndrome. Mov Disord 2006;21(11):18318.
79. Lim D, Khandhar S, Heath S, et al. Multiple target deep brain stimulation for
multiple sclerosis related and poststroke Holmes tremor. Stereotact Funct Neurosurg 2007;85(4):1449.
80. Siegfried J, Lippitz B. Chronic electrical stimulation of the VL-VPL complex and
of the pallidum in the treatment of movement disorders: personal experience
since 1982. Stereotact Funct Neurosurg 1994;62(14):715.
81. Benabid A, 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(2):20314.
82. Berk C, Carr J, Sinden M, et al. Thalamic deep brain stimulation for the treatment
of tremor due to multiple sclerosis: a prospective study of tremor and quality of
life. J Neurosurg 2002;97(4):81520.
83. Bittar R, Hyam J, Nandi D, et al. Thalamotomy versus thalamic stimulation for
multiple sclerosis tremor. J Clin Neurosci 2005;12(6):63842.
84. Brice J, McLellan L. Suppression of intention tremor by contingent deep-brain
stimulation. Lancet 1980;1(8180):12212.
85. Foote K, Seignourel P, Fernandez H, et al. Dual electrode thalamic deep brain
stimulation for the treatment of posttraumatic and multiple sclerosis tremor.
Neurosurgery 2006;58(4 Suppl 2):ONS2805.
86. Geny C, Nguyen J, Pollin B, et al. Improvement of severe postural cerebellar tremor
in multiple sclerosis by chronic thalamic stimulation. Mov Disord 1996;11(5):48994.
87. Hooper J, Taylor R, Pentland B, et al. A prospective study of thalamic deep brain
stimulation for the treatment of movement disorders in multiple sclerosis. Br J
Neurosurg 2002;16(2):1029.
88. Matsumoto J, Morrow D, Kaufman K, et al. Surgical therapy for tremor in multiple
sclerosis: an evaluation of outcome measures. Neurology 2001;57(10):187682.
89. Montgomery EJ, Baker K, Kinkel R, et al. Chronic thalamic stimulation for the
tremor of multiple sclerosis. Neurology 1999;53(3):6258.
90. Moringlane J, Spiegel J, Fuss G, et al. Improvement of upper limb ataxia and
intention tremor allowing cessation of thalamic electrostimulation after four
years. Mult Scler 2004;10(6):70810.
91. Nguyen J, Degos J. Thalamic stimulation and proximal tremor. A specific target
in the nucleus ventrointermedius thalami. Arch Neurol 1993;50(5):498500.
92. Plaha P, Khan S, Gill S. Bilateral stimulation of the caudal zona incerta nucleus
for tremor control. J Neurol Neurosurg Psychiatry 2008;79(5):50413.
93. Schulder M, Sernas T, Karimi R. Thalamic stimulation in patients with multiple
sclerosis: long-term follow-up. Stereotact Funct Neurosurg 2003;80(14):4855.
94. Schuurman P, Bosch D, Bossuyt P, et al. A comparison of continuous thalamic
stimulation and thalamotomy for suppression of severe tremor. N Engl J Med
2000;342(7):4618.
95. Wishart H, Roberts D, Roth R, et al. Chronic deep brain stimulation for the treatment of tremor in multiple sclerosis: review and case reports. J Neurol Neurosurg Psychiatry 2003;74(10):13927.
96. Foote K, Okun M. Ventralis intermedius plus ventralis oralis anterior and posterior deep brain stimulation for posttraumatic Holmes tremor: two leads may be
better than one: technical note. Neurosurgery 2005;56(Suppl 2):E445.
97. Fasano A, Mazzone P, Piano C, et al. GPi-DBS in Huntingtons disease: results
on motor function and cognition in a 72-year-old case. Mov Disord 2008;23(9):
128992.
98. Hebb M, Garcia R, Gaudet P, et al. Bilateral stimulation of the globus pallidus
internus to treat choreathetosis in Huntingtons disease: technical case report.
Neurosurgery 2006;58(2):E383.
99. Freund H, Barnikol U, Nolte D, et al. Subthalamic-thalamic DBS in a case with
spinocerebellar ataxia type 2 and severe tremor-A unusual clinical benefit.
Mov Disord 2007;22(5):7325.
100. Shimojima Y, Hashimoto T, Kaneko K, et al. Thalamic stimulation for disabling
tremor in a patient with spinocerebellar degeneration. Stereotact Funct Neurosurg 2005;83(4):1314.
101. Krack P, Pollak P, Limousin P, et al. Stimulation of subthalamic nucleus alleviates
tremor in Parkinsons disease. Lancet 1997;350(9092):1675.
102. Ghika J, Villemure J, Fankhauser H, et al. Efficiency and safety of bilateral
contemporaneous pallidal stimulation (deep brain stimulation) in levodoparesponsive patients with Parkinsons disease with severe motor fluctuations:
a 2-year follow-up review. J Neurosurg 1998;89(5):7138.
103. Krack P, Benazzouz A, Pollak P, et al. Treatment of tremor in Parkinsons disease
by subthalamic nucleus stimulation. Mov Disord 1998;13(6):90714.
104. Kumar R, Lozano A, Montgomery E, et al. Pallidotomy and deep brain stimulation of the palladium and subthalamic nucleus in advanced Parkinsons disease.
Mov Disord 1998;13(Suppl 1):7382.
105. Kumar R, Lozano A, Kim Y, et al. Double-blind evaluation of subthalamic nucleus
deep brain stimulation in advanced Parkinsons disease. Neurology 1998;51(3):
8505.
106. Limousin P, Krack P, Pollak P, et al. Electrical stimulation of the subthalamic
nucleus in advanced Parkinsons disease. N Engl J Med 1998;339(16):
110511.
107. Volkmann J, Sturm V, Weiss P, et al. Bilateral high-frequency stimulation of the
internal globus pallidus in advanced Parkinsons disease. Ann Neurol 1998;
44(6):95361.
108. Ardouin C, Klinger H, Limousin P, et al. The effect of bilateral subthalamic
nucleus stimulation on cognitive functions. Neurology 1999;52(6 Supp 2):
A514.
109. Burchiel K, Anderson V, Favre J, et al. Comparison of pallidal and subthalamic
nucleus deep brain stimulation for advanced Parkinsons disease: results of
a randomized, blinded pilot study. Neurosurgery 1999;45(6):137582.
110. Limousin P, Speelman J, Gielen F, et al. Multicentre European study of thalamic
stimulation in parkinsonian and essential tremor. J Neurol Neurosurg Psychiatry
1999;66(3):28996.
111. Moro E, Scerrati M, Romito L, et al. Chronic subthalamic nucleus stimulation
reduces medication requirements in Parkinsons disease. Neurology 1999;
53(1):8590.
112. Pinter M, Alesch F, Murg M, et al. Deep brain stimulation of the subthalamic
nucleus for control of extrapyramidal features in advanced idiopathic Parkinsons disease: one year follow-up. J Neural Transm 1999;106(78):693709.
113. Bejjani B, Dormont D, Pidoux B, et al. Bilateral subthalamic stimulation for
Parkinsons disease by using three-dimensional stereotactic magnetic resonance
imaging and electrophysiological guidance. J Neurosurg 2000;92(4):61525.
114. Houeto J, Damier P, Bejjani P, et al. Subthalamic stimulation in Parkinson
disease: a multidisciplinary approach. Arch Neurol 2000;57(4):4615.
115. Jahanshahi M, Ardouin C, Brown R, et al. The impact of deep brain stimulation
on executive function in Parkinsons disease. Brain 2000;123(Pt 6):114254.
671
672
Kluger et al
116. Molinuevo J, Valldeoriola F, Tolosa E, et al. Levodopa withdrawal after bilateral

subthalamic nucleus stimulation in advanced Parkinson disease. Arch Neurol
2000;57(7):9838.
117. Pillon B, Ardouin C, Damier P, et al. Neuropsychological changes between off
and on STN or GPi stimulation in Parkinsons disease. Neurology 2000;55(3):
4118.
C, Valldeoriola F, et al. Effects of bilateral subthalamic stimula118. Alegret M, Junque
tion on cognitive function in Parkinson disease. Arch Neurol 2001;58(8):12237.
119. Capus L, Melatini A, Zorzon M, et al. Chronic bilateral electrical stimulation of the
subthalamic nucleus for the treatment of advanced Parkinsons disease. Neurol
Sci 2001;22(1):578.
120. Deep Brain Sitmulation for Parkinsons Disease Study Group. Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in
Parkinsons disease. N Engl J Med 2001;345(13):95663.
121. Dujardin K, Defebvre L, Krystkowiak P, et al. Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinsons disease.
J Neurol 2001;248(7):60311.
122. Faist M, Xie J, Kurz D, et al. Effect of bilateral subthalamic nucleus stimulation on
gait in Parkinsons disease. Brain 2001;124(Pt 8):1590600.
123. Lopiano L, Rizzone M, Bergamasco B, et al. Deep brain stimulation of the subthalamic nucleus: clinical effectiveness and safety. Neurology 2001;56(4):5524.
124. Lopiano L, Rizzone M, Perozzo P, et al. Deep brain stimulation of the subthalamic
nucleus: selection of patients and clinical results. Neurol Sci 2001;22(1):678.
125. Volkmann J, Allert N, Voges J, et al. Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD. Neurology 2001;56(4):54851.
126. Durif F, Lemaire J, Debilly B, et al. Long-term follow-up of globus pallidus chronic
stimulation in advanced Parkinsons disease. Mov Disord 2002;17(4):8037.
ndez R, Regidor I, Riva-Meana C, et al. Further supporting
127. Figueiras-Me
evidence of beneficial subthalamic stimulation in Parkinsons patients.
Neurology 2002;58(3):46970.
128. Just H, Ostergaard K. Health-related quality of life in patients with advanced
Parkinsons disease treated with deep brain stimulation of the subthalamic
nuclei. Mov Disord 2002;17(3):53945.
129. Lagrange E, Krack P, Moro E, et al. Bilateral subthalamic nucleus stimulation
improves health-related quality of life in PD. Neurology 2002;59(12):19768.
130. Loher T, Burgunder J, Pohle T, et al. Long-term pallidal deep brain stimulation in
patients with advanced Parkinson disease: 1-year follow-up study. J Neurosurg
2002;96(5):84453.
131. Martnez-Martn P, Valldeoriola F, Tolosa E, et al. Bilateral subthalamic nucleus
stimulation and quality of life in advanced Parkinsons disease. Mov Disord
2002;17(2):3727.
132. stergaard K, Sunde N, Dupont E. Effects of bilateral stimulation of the subthalamic nucleus in patients with severe Parkinsons disease and motor fluctuations. Mov Disord 2002;17(4):693700.
133. Romito L, Scerrati M, Contarino M, et al. Long-term follow up of subthalamic
nucleus stimulation in Parkinsons disease. Neurology 2002;58(10):154650.
134. Simuni T, Jaggi J, Mulholland H, et al. Bilateral stimulation of the subthalamic
nucleus in patients with Parkinson disease: a study of efficacy and safety. J Neurosurg 2002;96(4):66672.
135. Thobois S, Mertens P, Guenot M, et al. Subthalamic nucleus stimulation in
Parkinsons disease: clinical evaluation of 18 patients. J Neurol 2002;249(5):52934.
136. Vesper J, Klostermann F, Stockhammer F, et al. Results of chronic subthalamic

nucleus stimulation for Parkinsons disease: a 1-year follow-up study. Surg
Neurol 2002;57(5):30611.
137. Vingerhoets F, Villemure J, Temperli P, et al. Subthalamic DBS replaces levodopa
in Parkinsons disease: two-year follow-up. Neurology 2002;58(3):396401.
138. Voges J, Volkmann J, Allert N, et al. Bilateral high-frequency stimulation in the
subthalamic nucleus for the treatment of Parkinson disease: correlation of therapeutic effect with anatomical electrode position. J Neurosurg 2002;96(2):26979.
139. Welter ML, Houeto JL, Tezenas du Montcel S, et al. Clinical predictive factors of
subthalamic stimulation in Parkinsons disease. Brain 2002;125(Pt 3):57583.
140. Chen C, Lee S, Wu T, et al. Short-term effect of bilateral subthalamic stimulation
for advanced Parkinsons disease. Chang Gung Med J 2003;26(5):34451.
141. Daniele A, Albanese A, Contarino M, et al. Cognitive and behavioural effects of
chronic stimulation of the subthalamic nucleus in patients with Parkinsons
disease. J Neurol Neurosurg Psychiatry 2003;74(2):17582.
142. Funkiewiez A, Ardouin C, Krack P, et al. Acute psychotropic effects of bilateral
subthalamic nucleus stimulation and levodopa in Parkinsons disease. Mov Disord 2003;18(5):52430.
143. Herzog J, Volkmann J, Krack P, et al. Two-year follow-up of subthalamic deep
brain stimulation in Parkinsons disease. Mov Disord 2003;18(11):13327.
144. Kleiner-Fisman G, Fisman D, Sime E, et al. Long-term follow up of bilateral deep
brain stimulation of the subthalamic nucleus in patients with advanced Parkinson disease. J Neurosurg 2003;99(3):48995.
145. Krack P, Batir A, Blercom NV, et al. Five-year follow-up of bilateral stimulation of
the subthalamic nucleus in advanced Parkinsons disease. N Engl J Med 2003;
349(20):192534.
146. Pahwa R, Wilkinson S, Overman J, et al. Bilateral subthalamic stimulation in
patients with Parkinson disease: long-term follow up. J Neurosurg 2003;99(1):
717.
147. Varma T, Fox S, Eldridge P, et al. Deep brain stimulation of the subthalamic
nucleus: effectiveness in advanced Parkinsons disease patients previously
reliant on apomorphine. J Neurol Neurosurg Psychiatry 2003;74(2):1704.
148. Volkmann J, Allert N, Voges J, et al. Long-term results of bilateral pallidal stimulation in Parkinsons disease. Ann Neurol 2004;55(6):8715.
149. Liang G, Chou K, Baltuch G, et al. Long-term outcomes of bilateral subthalamic
nucleus stimulation in patients with advanced Parkinsons disease. Stereotact
Funct Neurosurg 2006;84(56):2217.
150. Portman A, Laar Tv, Staal M, et al. Chronic stimulation of the subthalamic
nucleus increases daily on-time without dyskinesia in advanced Parkinsons
disease. Parkinsonism Relat Disord 2006;12(3):1438.
151. Derost P, Ouchchane L, Morand D, et al. Is DBS-STN appropriate to treat severe
Parkinson disease in an elderly population? Neurology 2007;68(17):134555.
152. Gan J, Xie-Brustolin J, Mertens P, et al. Bilateral subthalamic nucleus stimulation in
advanced Parkinsons disease: three years follow-up. J Neurol 2007;254(1):99106.
153. Rodrigues J, Walters S, Watson P, et al. Globus pallidus stimulation in advanced
Parkinsons disease. J Clin Neurosci 2007;14(3):20815.
154. Schupbach W, Maltete D, Houeto J, et al. Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial. Neurology 2007;68(4):26771.
155. Tir M, Devos D, Blond S, et al. Exhaustive, one-year follow-up of subthalamic
nucleus deep brain stimulation in a large, single-center cohort of parkinsonian
patients. Neurosurgery 2007;61(2):297304.
673
674
Kluger et al
156. Vesper J, Haak S, Ostertag C, et al. Subthalamic nucleus deep brain stimulation
in elderly patientsanalysis of outcome and complications. BMC Neurol 2007;
16(7):7.
gis J, et al. Effects of chronic subthalamic stimulation
157. Witjas T, Kaphan E, Re
on nonmotor fluctuations in Parkinsons disease. Mov Disord 2007;22(12):
172934.
158. Zibetti M, Torre E, Cinquepalmi A, et al. Motor and nonmotor symptom follow-up
in parkinsonian patients after deep brain stimulation of the subthalamic nucleus.
Eur Neurol 2007;58(4):21823.
159. Wider C, Pollo C, Bloch J, et al. Long-term outcome of 50 consecutive Parkinsons disease patients treated with subthalamic deep brain stimulation. Parkinsonism Relat Disord 2008;14(2):1149.
160. Pahwa R, Lyons K, Wilkinson S, et al. Long-term evaluation of deep brain stimulation of the thalamus. J Neurosurg 2006;104(4):50612.
161. Lee J, Kondziolka D. Thalamic deep brain stimulation for management of essential tremor. J Neurosurg 2005;103(3):4003.
162. Putzke J, Uitti R, Obwegeser A, et al. Bilateral thalamic deep brain stimulation:
midline tremor control. J Neurol Neurosurg Psychiatry 2005;76(5):68490.
163. Putzke J, Wharen R Jr, Obwegeser A, et al. Thalamic deep brain stimulation for
essential tremor: recommendations for long-term outcome analysis. Can J Neurol Sci 2004;31(3):33342.
164. Kumar R, Lozano A, Sime E, et al. Long-term follow-up of thalamic deep brain
stimulation for essential and parkinsonian tremor. Neurology 2003;61(11):
16014.
165. Bryant J, Salles AD, Cabatan C, et al. The impact of thalamic stimulation on
activities of daily living for essential tremor. Surg Neurol 2003;59(6):47984.
166. Fields J, Troster A, Woods S, et al. Neuropsychological and quality of life
outcomes 12 months after unilateral thalamic stimulation for essential tremor.
J Neurol Neurosurg Psychiatry 2003;74(3):30511.
167. Rehncrona S, Johnels B, Widner H, et al. Long-term efficacy of thalamic deep
brain stimulation for tremor: double-blind assessments. Mov Disord 2003;
18(2):16370.
168. Koller W, Lyons K, Wilkinson S, et al. Long-term safety and efficacy of unilateral
deep brain stimulation of the thalamus in essential tremor. Mov Disord 2001;
16(3):4648.
169. Obwegeser A, Uitti R, Witte R, et al. Quantitative and qualitative outcome
measures after thalamic deep brain stimulation to treat disabling tremors.
Neurosurgery 2001;48(2):27481.
170. Pahwa R, Lyons K, Wilkinson S, et al. Comparison of thalamotomy to deep brain
stimulation of the thalamus in essential tremor. Mov Disord 2001;16(1):1403.
171. Krauss J, Simpson R Jr, Ondo W, et al. Concepts and methods in chronic
thalamic stimulation for treatment of tremor: technique and application. Neurosurgery 2001;48(3):53541.
172. Pahwa R, Lyons K, Wilkinson S, et al. Bilateral thalamic stimulation for the treatment of essential tremor. Neurology 1999;53(7):144750.
173. Kumar K, Kelly M, Toth C. Deep brain stimulation of the ventral intermediate
nucleus of the thalamus for control of tremors in Parkinsons disease and essential tremor. Stereotact Funct Neurosurg 1999;72(1):4761.
174. Koller W, Lyons K, Wilkinson S, et al. Efficacy of unilateral deep brain stimulation
of the VIM nucleus of the thalamus for essential head tremor. Mov Disord 1999;
14(5):84750.
175. Hariz M, Shamsgovara P, Johansson F, et al. Tolerance and tremor rebound

following long-term chronic thalamic stimulation for parkinsonian and essential
tremor. Stereotact Funct Neurosurg 1999;72(24):20818.
176. Lyons K, Pahwa R, Busenbark K, et al. Improvements in daily functioning after
deep brain stimulation of the thalamus for intractable tremor. Mov Disord
1998;13(4):6902.
177. Ondo W, Jankovic J, Schwartz K, et al. Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinsons disease tremor. Neurology
1998;51(4):10639.
178. 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(3):2929.
179. Hubble J, Busenbark K, Wilkinson S, et al. Deep brain stimulation for essential
tremor. Neurology 1996;46(4):11503.
180. 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(1):628.
181. Vercueil L, Pollak P, Fraix V, et al. Deep brain stimulation in the treatment of
severe dystonia. J Neurol 2001;248(8):695700.
182. Bereznai B, Steude U, Seelos K, et al. Chronic high-frequency globus pallidus
internus stimulation in different types of dystonia: a clinical, video, and MRI
report of six patients presenting with segmental, cervical, and generalized dystonia. Mov Disord 2002;17(1):13844.
183. Krauss J, Loher T, Pohle T, et al. Pallidal deep brain stimulation in patients with
cervical dystonia and severe cervical dyskinesias with cervical myelopathy.
184. Cif L, Fertit HE, Vayssiere N, et al. Treatment of dystonic syndromes by chronic
electrical stimulation of the internal globus pallidus. J Neurosurg Sci 2003;47(1):
525.
185. Katayama Y, Fukaya C, Kobayashi K, et al. Chronic stimulation of the globus pallidus internus for control of primary generalized dystonia. Acta Neurochir Suppl
2003;87:1258.
186. Krauss J, Loher T, Weigel R, et al. Chronic stimulation of the globus pallidus
internus for treatment of non-dYT1 generalized dystonia and choreoathetosis:
2-year follow up. J Neurosurg Sci 2003;98(4):78592.
187. Kupsch A, Klaffke S, Kuhn A, et al. The effects of frequency in pallidal deep
brain stimulation for primary dystonia. J Neurol 2003;250(10):12015.
188. Yianni J, Bain P, Giladi N, et al. Globus pallidus internus deep brain stimulation
for dystonic conditions: a prospective audit. Mov Disord 2003;18(4):43642.
189. Yianni J, Bain P, Gregory R, et al. Post-operative progress of dystonia patients
following globus pallidus internus deep brain stimulation. Eur J Neurol 2003;
10(3):23947.
190. Cif L, Valente E, Hemm S, et al. Deep brain stimulation in myoclonus-dystonia
syndrome. Mov Disord 2004;19(6):7247.
191. Coubes P, Cif L, Fertit HE, et al. Electrical stimulation of the globus pallidus
internus in patients with primary generalized dystonia: long-term results. J Neurosurg 2004;101(2):18994.
192. Detante O, Vercueil L, Thobois S, et al. Globus pallidus internus stimulation in
primary generalized dystonia: a H215O PETstudy. Brain 2004;127(Pt 8):1899908.
193. Krause M, Fogel W, Kloss M, et al. Pallidal stimulation for dystonia. Neurosurgery 2004;55(6):13618.
675
676
Kluger et al
194. Trottenberg T, Volkmann J, Deuschl G, et al. Treatment of severe tardive dystonia with pallidal deep brain stimulation. Neurology 2005;64(2):3446.
195. Vayssiere N, Gaag NVd, Cif L, et al. Deep brain stimulation for dystonia confirming a somatotopic organization in the globus pallidus internus. J Neurosurg
2004;101(2):1818.
196. Bittar R, Yianni J, Wang S, et al. Deep brain stimulation for generalised dystonia
and spasmodic torticollis. J Clin Neurosci 2005;12(1):126.
197. Castelnau P, Cif L, Valente E, et al. Pallidal stimulation improves pantothenate
kinase-associated neurodegeneration. Ann Neurol 2005;57(5):73841.
198. Chou K, Hurtig H, Jaggi J, et al. Bilateral subthalamic nucleus deep brain stimulation in a patient with cervical dystonia and essential tremor. Mov Disord 2005;
20(3):37780.
199. Zorzi G, Marras C, Nardocci N, et al. Stimulation of the globus pallidus internus
for childhood-onset dystonia. Mov Disord 2005;20(9):1194200.
200. Diamond A, Shahed J, Azher S, et al. Globus pallidus deep brain stimulation in
dystonia. Mov Disord 2006;21(5):6925.
201. Starr P, Turner R, Rau G, et al. Microelectrode-guided implantation of deep brain
stimulators into the globus pallidus internus for dystonia: techniques, electrode
locations, and outcomes. J Neurosurg 2006;104(4):488501.
202. Zhang J, Zhang K, Wang Z, et al. Deep brain stimulation in the treatment of
secondary dystonia. Chin Med J (Engl) 2006;119(24):206974.
203. Alterman R, Miravite J, Weisz D, et al. Sixty hertz pallidal deep brain stimulation
for primary torsion dystonia. Neurology 2007;69(7):6818.
204. Damier P, Thobois S, Witjas T, et al. Bilateral deep brain stimulation of the globus
pallidus to treat tardive dyskinesia. Arch Gen Psychiatry 2007;64(2):1706.
205. Evidente V, Lyons M, Wheeler M, et al. First case of X-linked dystonia-parkinsonism (Lubag) to demonstrate a response to bilateral pallidal stimulation.
Mov Disord 2007;22(12):17903.
206. Grips E, Blahak C, Capelle H, et al. Patterns of reoccurrence of segmental dystonia after discontinuation of deep brain stimulation. J Neurol Neurosurg Psychiatry 2007;78(3):31820.
207. Kiss Z, Doig-Beyaert K, Eliasziw M, et al. The Canadian multicentre study of
deep brain stimulation for cervical dystonia. Brain 2007;130(Pt 11):287986.
208. Kleiner-Fisman G, Liang G, Moberg P, et al. Subthalamic nucleus deep brain
stimulation for severe idiopathic dystonia: impact on severity, neuropsychological status, and quality of life. J Neurosurg 2007;107(1):2936.
209. Novak K, Nenonene E, Bernstein L, et al. Successful bilateral subthalamic
nucleus stimulation for segmental dystonia after unilateral pallidotomy. Stereotact Funct Neurosurg 2008;86(2):806.
210. Tisch S, Zrinzo L, Limousin P, et al. Effect of electrode contact location on clinical efficacy of pallidal deep brain stimulation in primary generalised dystonia.
211. Vidailhet M, Vercueil L, Houeto J, et al. Bilateral, pallidal, deep-brain stimulation
in primary generalised dystonia: a prospective 3 year follow-up study. Lancet
Neurol 2007;6(3):2239.
212. Loher T, Capelle H, Kaelin-Lang A, et al. Deep brain stimulation for dystonia:
outcome at long-term follow-up. J Neurol 2008;255(6):8814.
213. Sako W, Goto S, Shimazu H, et al. Bilateral deep brain stimulation of the globus
pallidus internus in tardive dystonia. Mov Disord 2008;23(13):192931.
214. Welter M, Mallet L, Houeto J, et al. Internal pallidal and thalamic stimulation in
patients with Tourette syndrome. Arch Neurol 2008;65(7):9527.
215. Bajwa R, Lotbinie`re Ad, King R, et al. Deep brain stimulation in Tourettes
syndrome. Mov Disord 2007;22(9):134650.
216. Shahed J, Poysky J, Kenney C, et al. GPi deep brain stimulation for Tourette
syndrome improves tics and psychiatric comorbidities. Neurology 2007;68(2):
15960.
217. Maciunas R, Maddux B, Riley D, et al. Prospective randomized double-blind trial
of bilateral thalamic deep brain stimulation in adults with Tourette syndrome.
J Neurosurg 2007;107(5):100414.
218. Ackermans L, Temel Y, Cath D, et al. Deep brain stimulation in Tourettes
syndrome: two targets? Mov Disord 2006;21(5):70913.
219. Flaherty A, Williams Z, Amirnovin R, et al. Deep brain stimulation of the anterior
internal capsule for the treatment of Tourette syndrome: technical case report.
Neurosurgery 2005;57(Suppl 4):E403.
220. Diederich N, Kalteis K, Stamenkovic M, et al. Efficient internal pallidal stimulation
in Gilles de la Tourette syndrome: a case report. Mov Disord 2005;20(11):
14969.
221. Houeto J, Karachi C, Mallet L, et al. Tourettes syndrome and deep brain stimulation. J Neurol Neurosurg Psychiatry 2005;76(7):9925.
222. Visser-Vandewalle V, Temel Y, Boon P, et al. Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable Tourette syndrome. Report of
three cases. J Neurosurg 2003;99(6):1094100.
223. Vandewalle V, Linden Cvd, Groenewegen H, et al. Stereotactic treatment of
Gilles de la Tourette syndrome by high frequency stimulation of thalamus.
Lancet 1999;353(9154):724.
224. Moro E, Lang A, Strafella A, et al. Bilateral globus pallidus stimulation for Huntingtons disease. Ann Neurol 2004;56(2):2904.
225. Kudo M, Goto S, Nishikawa S. Bilateral thalamic stimulation for Holmes tremor
caused by unilateral brainstem lesion. Mov Disord 2001;16(1):1704.
677

Surgical Movement Disorders

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Surgical Movement Disorders

Uploaded by

Copyright:

Available Formats

Surgical Treatment of

Surgical Treatment of Movement Disorders

Surgical Treatment of Movement Disorders

Fig. 1. Multidisciplinary team.

issues, QOL, target choice, staged versus simultaneous implantation if bilateral

Surgical Treatment of Movement Disorders

1- RED FLAGfrequently disoriented or severe cognitive difficulties, severe memory

No. of Patients (%)

Arrhythmia (junctional rhythm)

Laceration of soft palate

Perioperative (within 2 wk)

Arrhythmia (right bundle branch block)

Deep vein thrombosis

Surgical Treatment of Movement Disorders

No. of Patients (%)

more research is needed to determine if staged or simultaneous procedures have

S&E off 29.0/73.2

Surgical Treatment of Movement Disorders

Improves some aspects

Off time 89.7%

Off time 2.0/0.3 (85%)

Off time 49/19%

Off time decreased

Surgical Treatment of Movement Disorders

Off time 31/0%

BDI 10.5/8.5 (19.0%)

Off time 1.8/0.3 (83.3%)

Weight increase 75/8 kg

Off time 14.5/6 (58.6%)

S&E off 42/77 ( 83.3%)

Improved S&E off 22.9/70.0

Funkiewiez et al., 50 Prosp NC

BDI 13.9/11.5 (17.3%)

PDQ 83.2/54.3 (34.7%)

(continued on next page)

Surgical Treatment of Movement Disorders

Off time 1.6/1.0 (37.5%)

DRS 136/131 (3.7%)

Off time 44/20%

Off time 1.9/1.2 (36.8%)

S&E off 52/72 ( 38.5%)

DRS 135.9/137.4 (NS)

DRS 140.5/140.5 (NS)

S&E off 45.3/63.7

Surgical Treatment of Movement Disorders

Off time 1.55/0.11

Surgical Treatment of Movement Disorders

settings. Common stimulation-related side effects may include paresthesias due to

SPECIFIC MOVEMENT DISORDERS AND TARGETS

Pahwa et al., 2006160

46% (unilateral) and 78%

35%50% improvement on ADLs

Lee and Kondziolka, 2005161

75% improvement FTM TRS

64% improvement in handwriting

Putzke et al., 2005162

81% improvement FTM TRS

Putzke et al., 2004163

45% improvement FTM TRS

70% improvement in ADLs

Kumar et al., 2003164

62% improvement in FTM TRS

Tolerance to DBS developed in 2 of