Predictive factors of outcome in primary cervical dystonia following pallidal deep brain stimulation.
ABSTRACT Improvement after bilateral globus pallidus internus deep brain stimulation (DBS) in primary generalized dystonia has been negatively associated with disease duration and age, but no predictive factors have been identified in primary cervical dystonia (CD).
Patients treated with bilateral globus pallidus internus DBS for primary CD from 2 DBS centers with preoperative and postoperative Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS) were studied retrospectively to explore possible predictors of response.
Patients showed significantly improved TWSTRS total and severity scores (n = 28, mean 55.6% and 50.8%, respectively, both P < .001). Patients with lateral shift at baseline had less improvement in TWSTRS severity subscores (P = .02). No correlations between outcomes and disease duration, age at dystonia onset or surgery, baseline scores, or other included variables were found.
Although this is the largest study supporting efficacy of bilateral pallidal DBS in primary CD, no major clinical predictive outcomes of surgical benefit were identified. © 2013 Movement Disorder Society.
- SourceAvailable from: Christian K E Moll[Show abstract] [Hide abstract]
ABSTRACT: The origin of asymmetric clinical manifestation of symptoms in patients suffering from cervical dystonia (CD) is hitherto poorly understood. Dysregulated neuronal activity in the basal ganglia has been suggested to have a role in the pathophysiology of CD. Here, we re-assessed the question to what extent relative changes occur in the direct vs. indirect basal ganglia pathway in CD, whether these circuit changes are lateralized, and how these alterations relate to CD symptoms. To this end, we recorded ongoing single cell and local field potential (LFP) activity from the external (GPe) and internal pallidal segment (GPi) of 13 CD patients undergoing microelectrode-guided stereotactic surgery for deep brain stimulation in the GPi. We compared pallidal recordings from CD patients operated under local anaesthesia (LA) with those obtained in CD patients operated under general anaesthesia (GA). In awake patients, mean GPe discharge rate (52 Hz) was lower than that of GPi (72 Hz). Mean GPi discharge ipsilateral to the side of head turning was higher than contralateral and correlated with torticollis symptom severity. Lateralized differences were absent at the level of the GPe and in recordings from patients operated under GA. Furthermore, in the GPi of CD patients there was a subpopulation of theta-oscillatory cells with unique bursting characteristics. Power and coherence of GPe- and GPi-LFPs were dominated by a theta peak and also exhibited band-specific interhemispheric differences. Strong cross-frequency coupling of low-gamma amplitude to theta phase was a feature of pallidal LFPs recorded under LA, but not GA. These results indicate that CD is associated with an asymmetric pallidal outflow. Based on the finding of symmetric neuronal discharges in the GPe, we propose that an imbalanced interhemispheric direct pathway gain may be involved in CD pathophysiology.Frontiers in Systems Neuroscience 01/2014; 8:15.
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ABSTRACT: Selective peripheral denervation (SPD) and deep brain stimulation of the globus pallidus (GPi-DBS) are available surgical options for patients with medically refractory cervical dystonia (CD). There are few data available concerning whether patients who have unsatisfactory treatment effects after primary surgery benefit from a different type of subsequent surgery. The aim of this study was to assess whether combining these surgical procedures (SPD plus GPi-DBS) was effective in patients with unsatisfactory treatment effects after their initial surgery. Forty-one patients with medically refractory idiopathic CD underwent SPD and/or GPi-DBS. Patients who were dissatisfied with their primary surgery (SPD or GPi DBS) elected to subsequently undergo a different type of surgery. These patients were assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). SPD alone and GPi-DBS alone were performed in 16 and 21 patients, respectively. Four patients had unsatisfactory treatment effects after the initial surgery and subsequently underwent another type of surgery. Among them, two patients with persistent dystonia after SPD subsequently underwent GPi-DBS, and two other patients who had insufficient treatment effects following GPi-DBS were subsequently treated with SPD. All of these patients experienced sustained improvement from the combined surgical procedures according to the TWSTRS score during a long-term follow-up of 12-90 months. Patients with unsatisfactory treatment effects after an SPD or GPi-DBS experienced improvement from subsequently undergoing other types of surgery. Therefore, combined surgical procedures are additional surgical options with good outcomes in the treatment of patients with residual symptoms after their initial surgery.Acta Neurochirurgica 12/2014; · 1.79 Impact Factor
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ABSTRACT: Treatment of dystonia refractory to oral medications or botulinum toxin injections includes the use of deep brain stimulation (DBS). Expectations should be established based on patient-related factors, including type of dystonia, genetic cause, target symptoms, age at the time of surgery, disease duration, or the presence of fixed skeletal deformities. Premorbid conditions such as psychiatric illness and cognitive impairment should be considered. Target selection is an emerging issue in DBS for dystonia. Although efficacy has been established for targeting the globus pallidus internus for dystonia, other brain targets such as the subthalamic nucleus, thalamus, or cortex may be promising alternatives.Neurosurgery clinics of North America 01/2014; 25(1):59-75. · 1.73 Impact Factor
Predictive Factors of Outcome in
Primary Cervical Dystonia
Following Pallidal Deep Brain
Jennifer L. Witt, MD,1§Elena Moro, MD, PhD,2§
Rima S. Ash, MD,1Clement Hamani, MD,3
Philip A. Starr, MD, PhD,4Andres M. Lozano, MD, PhD,3
Mojgan Hodaie, MD,3Yu-Yan Poon, RN,2
Leslie C. Markun, MSc1and Jill L. Ostrem, MD1*
1Surgical Movement Disorders, Department of Neurology, University
of California, San Francisco, California, USA;2Movement Disorders
Centre, Toronto Western Hospital, University Health Network (UHN),
University of Toronto, Toronto, Ontario, Canada;3Division of
Neurosurgery, Toronto Western Hospital, University Health Network
(UHN), University of Toronto, Toronto, Ontario, Canada;4Surgical
Movement Disorders, Department of Neurological Surgery, University
of California, San Francisco, California, USA
Background: Improvement after bilateral globus pal-
lidus internus deep brain stimulation (DBS) in primary
generalized dystonia has been negatively associated
with disease duration and age, but no predictive
Methods: Patients treated with bilateral globus pallidus
internus DBS for primary CD from 2 DBS centers with
preoperative and postoperative Toronto Western Spas-
modic Torticollis Rating Scales (TWSTRS) were studied
TWSTRS total and severity scores (n528, mean
55.6% and 50.8%, respectively, both P<.001). Patients
with lateral shift at baseline had less improvement in
TWSTRS severity subscores (P5.02). No correlations
between outcomes and disease duration, age at dysto-
nia onset or surgery, baseline scores, or other included
variables were found.
supporting efficacy of bilateral pallidal DBS in primary
CD, no major clinical predictive outcomes of surgical
benefit were identified. V
and Movement Disorder Society
Key Words: globus pallidus; deep brain stimulation;
DBS; cervical dystonia
C 2013 International Parkinson
Cervical dystonia (CD), is defined by simultaneous
and sustained contraction of agonist and antagonist
neck muscles, sometimes including segmental involve-
ment of cranial (craniocervical dystonia [CCD]) or
brachial regions and frequently associated with pain and
disability.1,2Treatment with pharmacotherapy is often
minimal and/or limited by side effects.3Botulinum toxin
injections, recommended as first-line therapy,4are often
very effective, but not in all patients.3
Deep brain stimulation (DBS) therapy is an alter-
native for patients who fail nonsurgical treatments.
Efficacy has been reported in a number of small
series of CD and/or CCD patients.5–14Both the
globus pallidus internus (GPi) and the subthalamic
nucleus (STN) as the stimulation target have been
shown to be effective.15,16A range of improvement
in the total Toronto Western Spasmodic Torticollis
Rating Scale (TWSTRS) has been reported with GPi-
DBS (41.4% to 76%)9–14,17–21and an even wider
range when Burke Fahn Marsden Dystonia Rating
Scale Movement Score (BFMDRS MS) has been used
(0% to 90%).20,22–25Predictive factors associated
with outcome have not been identified yet in CD
(PGD), some studies have found no predictive fac-
tors of benefit,2,27,28while others have found a posi-
tive correlation with the DYT-1 status,23,29
negative correlation with age at time of surgery29,30
and duration of disease,30
years.31Application of these findings to CD, which
affects a different patient demographic, has not yet
been informed by evidence.
Here, we examined outcomes of treatment and fac-
tors associated with improvement in the largest series
to date of CD treated with bilateral GPi-DBS.
particularly over 15
Patients and Methods
Patients with primary CD or CCD treated with
bilateral GPi-DBS at the Toronto Western Hospital
(TWH) and the University of California, San Francisco
(UCSF) between January 1996 and October 2006
*Correspondence to: Dr. Jill L. Ostrem, Surgical Movement Disorders,
Department of Neurology, University of California, 1635 Divisadero St.,
Suite 520/530, San Francisco, CA 94115, USA; email@example.com
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online
version of this article.
Dr. Witt and Dr. Moro contributed equally to this work.
Received: 20 November 2012; Revised: 7 May 2013;
Accepted: 9 May 2013
Published online 20 June 2013 in Wiley Online Library
(wileyonlinelibrary.com). DOI: 10.1002/mds.25560
Movement Disorders, Vol. 28, No. 10, 2013
C E R V I C A LD Y S T O N I AO U T C O M E SF O RG P ID B S
were included in this retrospective observational study
with approval from each institution’s internal review
TWSTRS scores were included in the analysis if they
met the following inclusion criteria: treated with bilat-
eral GPi-DBS for idiopathic CCD or CD causing
severe functional impairment despite optimal pharma-
cotherapy (including botulinum toxin therapy), onset
at ?18 years of age, diagnosed by a movement
disorders neurologist, absence of secondary causes of
neurological exam except for dystonia, and normal
magnetic resonance imaging (MRI) of the brain.
Patients with mild upper extremity dystonia associated
with predominantly CD were not excluded. Data was
available for 17 patients treated at TWH and 11
patients treated at UCSF. Lead implantation method-
ology was similar at both centers and was performed
using MRI-based stereotaxy, microelectrode recording,
thresholds for adverse effects (Medtronic, Minneapo-
lis, Minnesota, USA). Methods used to assess the loca-
tion of DBS electrodes have been described.22,32
Briefly, 3D volumetric T1 and T2 and postoperative
axial images were fused. The anterior and posterior
commissures were registered and the location of the
tip of the electrodes was calculated relative to the
Percent improvement in TWSTRS total and severity
scores between baseline and last available follow-up
were compared between categorical groups including:
center, sex, tonic versus phasic, focal (CD) versus
segmental (CCD), first site of involvement (cranial vs
cervical), presence versus absence of intracranial hem-
orrhage on postoperative MRI scan, lateral shift at
baseline, and sagittal shift at baseline (missing data on
lateral and sagittal shift scores for 2 patients). Out-
comes were also correlated with interval variables
including: age of onset; duration of disease; age at sur-
gery; duration of follow-up; baseline total, severity,
disability, and pain subscores; final programming
parameters; and lead tip coordinates.
Descriptive analyses are reported as mean6SD
(range). TWSTRS total and severity scores were
compared between baseline and last follow-up using
Wilcoxon paired sign rank test. The Wilcoxon Mann-
Whitney test was used for comparisons of percent
TABLE 1. Patient outcomes, lead location, and programming parameters
TWSTRS total and subscores
at baseline and last follow-up
visit, mean6SD (range)
(220 to 100)b
(245 to 100)b
DBS lead tip coordinates,
mean (SD), mma
X: lateral total
Y: anterior total
Z: ventral total
Average DBS programming
P5.34 20.4 (1.7)
aDistance in mm from the midpoint of line connecting the anterior and posterior commissures.
bP?.0001 by Wilcoxon signed-rank test.
TWSTRS, Toronto Western Spasmodic Torticollis Rating Scale; DBS, deep brain stimulation; TWH, Toronto Western Hospital; UCSF, University of California,
San Francisco; PW, pulse width.
W I T T E TA L .
Movement Disorders, Vol. 28, No. 10, 2013
change in TWSTRS total and severity scores between
categorical groups. Spearman coefficients were calcu-
lated for correlations between outcomes and demo-
graphic and clinical independent variables. P values
were considered significant at <.05. The STATA 11.1
software package was used.
Twenty-eight patients (9 male/19 female) were
included in the analysis. Average age at surgery was
56.0610.4 (range, 33–73) years, age at CD onset
45.1611.8 (range, 23–68) years, duration of disease
13.367.8 (range, 2–38) years, and length of DBS
treatment to last follow-up visit 33.7625.0 (range,
Patients experienced a mean 55.6%624.4% (range,
8.5% to 100%) improvement in TWSTRS total score
(P<.0001) with similar improvement in subscores.
DBS parameters and lead location were typical of
what has been described in the literature (Table 1).
TWH lead tips were somewhat more posterior than
UCSF leads (left P5.09, right P5.01), but the mean
outcomes were the same between centers (TWSTRS
total P5.87, TWSTRS severity P5.36).
There were 3 asymptomatic hemorrhages (TWH,
1 patient; UCSF, 2 patients). Two patients had lead
repositioning due to suboptimal initial placement
(TWH, 1 patient; UCSF, 1 patient). One patient
(UCSF) developed an infection after a routine battery
patient underwent reimplantation after the infection
Outcomes were not significantly different between
any of the categorical variables except for presence
versus absence of lateral shift at baseline (Table 2).
Percent improvement in TWSTRS severity was signifi-
cantly higher in patients without lateral shift (P5.02).
Length of follow-up did not correlate with total or
Demographic variables including age of onset, dura-
tion of disease (Fig. 1), baseline disease severity, age at
surgery, lead tip coordinates, and DBS programming
TABLE 2. Comparison of outcomes between categorical
Location of dystonia
Type of movementb
Initial site of
Lateral shift at
Sagittal shift at
aValues are mean6SD percent improvement.
bOne patient missing data.
cAll asymptomatic hemorrhages (TWH51; UCSF52).
dTwo patients were missing data.
TWSTRS, Toronto Western Spasmodic Torticollis Rating Scale; TWH,
Toronto Western Hospital; UCSF, University of California, San Francisco.
FIG. 1. Disease duration did not correlate with improvement in
TWSTRS Total or TWSTRS Severity Score. A: Percent improvement in
rho520.236, P5.23 (NS). B: Percent improvement in total TWSTRS
severity versus duration of disease Spearman’s rho520.112, P5.57
(NS). NS, not significant; TWSTRS, Toronto Western Spasmodic
Torticollis Rating Scales. [Color figure can be viewed in the online
issue, which is available at wileyonlinelibrary.com.]
C E R V I C A LD Y S T O N I AO U T C O M E S F O RG P ID B S
Movement Disorders, Vol. 28, No. 10, 2013
parameters at last follow-up visit were also not signifi-
cantly correlated with outcomes.
This is the largest series of patients with primary
CD treated with bilateral GPi-DBS reported to date,
providing supportive evidence for the efficacy of this
treatment. The presence of lateral shift was the only
factor negatively correlated to postsurgical outcome
(TWSTRS severity subscores). The follow-up in this
study was broad, from 4 to 97 months, and demon-
strates that improvement can be seen early and sus-
tained for over 8 years. The improvement in total
TWSTRS was comparable to the results published in
other series.8–14Whereas age at time of surgery and
disease duration have been identified as possible nega-
tive predictive factors of benefit in PGD,29–31our
study did not show this to be true and is consistent
with previous reports in CD.2,27,28PGD often begins
at a younger age than CD, and differences in brain
maturity between pediatric and adult populations
could account for the discrepancy in the effect of dis-
ease duration on DBS responsiveness.
Although the presence of lateral shift at baseline
was associated with significantly less improvement in
TWSTRS severity subscores, the total TWSTRS, dis-
ability and pain subscores were not different between
these groups, questioning the clinical applicability of
this finding. One hypothesis which may warrant fur-
ther study is the possibility that lateral shift could be
associated with secondary or comorbid degenerative
cervical spine changes that would not be expected to
be corrected with DBS.
There were no significant correlations between lead
tip coordinates and outcome in our combined series,
consistent with a prior TWH report.26In the present
series, TWH tips were more posterior (reached signifi-
cance on the right hemisphere) compared to those at
UCSF. There was also a nonsignificant trend for the
TWH-placed lead tips to be deeper. The active con-
tacts were most commonly the second or third electro-
des at both centers. Outcomes between the 2 centers
did not differ.
This study is limited by several factors. The design
was retrospective with nonblinded rating. We did not
explore in detail the degree of baseline degenerative
cervical spine changes. The sample size may have been
too small to demonstrate significance in the factors
that were included in the analysis. Larger, prospective
studies would be useful and may also be capable of
detecting predictors using cluster analysis.33
STN-DBS has also been shown to improve CD, with
outcomes similar to what was shown in this study.16
To date there have been no comparison studies evalu-
ating the efficacy these 2 brain targets in dystonia, but
preliminary studies suggest they will likely have differ-
ent stimulation-induced side effects.15,16
In conclusion, this study provides evidence that
bilateral GPi-DBS improves medically refractory pri-
mary CD even with long disease duration and
advanced age. Although baseline lateral shift was asso-
ciated with less improvement in severity subscale,
these patients still had overall improvement in disabil-
ity and pain. There remains a need for further pro-
spective studies of larger samples to explore additional
predictive factors and to evaluate target selection.
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