Tourette Syndrome Deep Brain Stimulation: A Review and UpdatedRecommendations
Lauren E. Schrock, MD,1 Jonathan W. Mink, MD, PhD,2 Douglas W. Woods, PhD,3 Mauro Porta, MD,4 Dominico Servello, MD,5
Veerle Visser-Vandewalle, MD, PhD,6 Peter A. Silburn, MD,7 Thomas Foltynie, MRCP, PhD,8 Harrison C. Walker, MD,9
Joohi Shahed-Jimenez, MD,10 Rodolfo Savica, MD,1 Bryan T. Klassen, MD,11 Andre G. Machado, MD,12 Kelly D. Foote, MD,13
Jian-Guo Zhang, MD, PhD,14 Wei Hu, MD, PhD,11,14 Linda Ackermans, MD, PhD,15 Yasin Temel, MD, PhD,15
Zoltan Mari, MD,16 Barbara K. Changizi, MD,17 Andres Lozano, MD,18 M. Auyeung, MD,19 Takanobu Kaido, MD, PhD,20
Yves Agid, MD, PhD,21 Marie L. Welter, MD, PhD,22 Suketu M. Khandhar, MD,23 Alon G. Mogilner, MD, PhD,24
Michael H. Pourfar, MD,24 Benjamin L. Walter, MD,25 Jorge L. Juncos, MD,26 Robert E. Gross, MD,27 Jens Kuhn, MD,28
James F. Leckman, MD,29 Joseph A Neimat, MD,30 Michael S. Okun, MD,13* on behalf of theand Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group
1Department of Neurology, University of Utah, Salt Lake City, Utah, USA2Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
3Department of Psychology, Texas A&M University, College Station, Texas, USA4Tourette Centre, IRCCS Galeazzi Hospital, Milan, Italy
5Functional Neurosurgical Unit, IRCCS Galeazzi Milano, Milan, Italy6Department of Stereotactic and Functional Neurosurgery, University of Cologne, Cologne, Germany
7Royal Brisbane and Women’s Hospital, School of Medicine, University of Queensland, Brisbane, Queensland, Australia8University College London Institute of Neurology, London, United Kingdom
9Department of Neurology, University of Alabama Birmingham, Birmingham, Alabama, USA10Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
11Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA12Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA
13Departments of Neurology, Neurosurgery, and Psychiatry, University of Florida Center for Movement Disorders and Neurorestoration,
Gainesville, Florida, USA14Department of Neurosurgery, Beijing Tiantan Hospital, Capital University of Medical Sciences, Beijing, China
15Department of Neurosurgery, Maastricht University Medical Center, The Netherlands16Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA
17Departments of Neurology and Psychiatry, The Ohio State University Wexner Medical Center, Ohio, USA18Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada
19Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, SAR China20Department of Neurosurgery, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan
21Institut du Cerveau et de la Moelle Epiniere (ICM), CHU Piti�e-Salpetriere, Paris, France22Centre de Recherche de l’Institut du Cerveau et de la Moelle �epiniere (CRICM), Universit�e Pierre et Marie Curie-Paris 6, Paris,
France23Northern California Kaiser Permanente, Surgical Movement Disorders Program, Sacramento, California, USA
24Departments of Neurosurgery and Neurology, New York University, Langone Medical Center, New York, New York, United States of
America25Movement Disorders Center, Neurological Institute, University Hospitals and Case Western Reserve University School of Medicine, South
Euclid, Ohio, USA26Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
27Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, USA28Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany
29Child Study Center and the Yale Center for Clinical Investigation, Yale University School of Medicine, New Haven, Connecticut, USA30Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
------------------------------------------------------------------------------------------------------------------------------*Correspondence to: Michael S. Okun, MD, 3450 Hull Road, Department of Neurology, Center for Movement Disorders and Neurorestoration, Gaines-ville, FL 32607, E-mail: [email protected]
Funding agencies:
Relevant conflicts of interest/financial disclosures: Nothing to report.Author roles may be found in the online version of this article.
Received: 4 April 2014; Revised: 6 October 2014; Accepted: 8 October 2014
Published online 00 Month 2014 in Wiley Online Library(wileyonlinelibrary.com). DOI: 10.1002/mds.26094
R E V I E W
Movement Disorders, Vol. 00, No. 00, 2014 1
ABSTRACT: Deep brain stimulation (DBS) mayimprove disabling tics in severely affected medicationand behaviorally resistant Tourette syndrome (TS). Herewe review all reported cases of TS DBS and provideupdated recommendations for selection, assessment,and management of potential TS DBS cases based onthe literature and implantation experience. Candidatesshould have a Diagnostic and Statistical Manual of Men-tal Disorders, Fifth Edition (DSM V) diagnosis of TS withsevere motor and vocal tics, which despite exhaustivemedical and behavioral treatment trials result in signifi-cant impairment. Deep brain stimulation should beoffered to patients only by experienced DBS centersafter evaluation by a multidisciplinary team. Rigorouspreoperative and postoperative outcome measures oftics and associated comorbidities should be used. Ticsand comorbid neuropsychiatric conditions should beoptimally treated per current expert standards, and ticsshould be the major cause of disability. Psychogenictics, embellishment, and malingering should be recog-
nized and addressed. We have removed the previouslysuggested 25-year-old age limit, with the specificationthat a multidisciplinary team approach for screening isemployed. A local ethics committee or institutionalreview board should be consulted for consideration ofcases involving persons younger than 18 years of age,as well as in cases with urgent indications. Tourettesyndrome patients represent a unique and complexpopulation, and studies reveal a higher risk for post-DBS complications. Successes and failures have beenreported for multiple brain targets; however, the optimalsurgical approach remains unknown. Tourette syndromeDBS, though still evolving, is a promising approach fora subset of medication refractory and severely affectedpatients. VC 2014 International Parkinson and MovementDisorder Society
Key Words: Tourette syndrome; DBS; guidelines;deep brain stimulation
Tourette syndrome (TS) is a chronic neurodevelop-mental disorder characterized by motor and phonictics that by definition occur with a childhood onset.1
The syndrome is commonly associated with other neu-ropsychiatric comorbidities (eg, attention deficit hyper-activity disorder [ADHD], obsessive compulsivefeatures [OCD], and other behavioral manifestations).In most TS cases, the motor manifestations can bemanaged using TS education, comprehensive behav-ioral intervention for tics (CBIT), or a variety of medi-cations.2-4 The natural history of TS is that mostpatients will experience improvement of tics in lateadolescence or early adulthood.5,6 However, a subsetof patients will continue to experience disabling ticsdespite optimal medication and behavioral manage-ment. For severely affected patients, deep brain stimu-lation (DBS) has the potential to improve refractoryand disabling symptoms.
Methods
An experienced group of physicians participating inthe Tourette Syndrome Association (TSA) Interna-tional DBS Database/Registry, and also activelyinvolved in managing TS DBS patients, reviewed the2006 TSA guidelines7 and examined all reported casesof TS DBS. The TSA Database/Registry groupaccepted complete information sets on outcomes fromTS DBS (database entry), as well as registration ofcases performed with or without outcome information(registry entry). The group summarized the literature(Table 1) and based on their collective experience
with TS DBS provided suggested updates (Table 2)and a consensus opinion on the TSA recommendationsput in place in 2006.7
Literature Review
Deep brain stimulation is an established treatmentfor Parkinson’s disease (PD),8-12 essential tremor,13,14
dystonia,15-17 and obsessive-compulsive disorder,18,19
and has been granted either full Food and Drug Admin-istration (FDA) approval (PD, essential tremor), or ahumanitarian device exemption (FDA; dystonia, OCD)for each of these indications (in the United States).Many studies and position papers detail careful andmeticulous techniques for screening patients forDBS,13,16,20-22 including a few reports for TSpatients.23,24 General guidelines for selecting individualTS patients for DBS therapy and for managing thempreoperatively and postoperatively will have the poten-tial to improve risk–benefit ratios. The importance ofrigorous preoperative assessment, patient selection, DBSteam expertise and experience, as well as postoperativemanagement has been demonstrated previously, espe-cially when groups have studied cohorts of patientswho have failed DBS therapy.25,26 Because TS is achildhood-onset disorder, often with complex clinicalfeatures, a waxing and waning course, and frequentneuropsychiatric comorbidities, the evaluation ofpatients has a greater level of complexity than many ofthe other current DBS indications.In 2005, the TSA hosted a meeting of physicians
with experience and expertise in TS and DBS to
S C H R O C K E T A L
2 Movement Disorders, Vol. 00, No. 00, 2014
TABLE1.Review
ofreportedTSDBScases
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
Servelloet
al.,
2008
61CM
-Pfc,Voa
18(15M
,3F)
17–47
8(2
�18
yrs)
3–18
mo
Case
series
IV1.YGTSS
64.7%
mean
improvem
ent
None
reported
Yes(9
with
SIB;
3cervicalmyelop-
athy,1disc
herniation,
2unableto
eat)
No1.
Transientstim-induced
vertigo
&visualAE
2.Poor
scalpincision
healingdueto
repetitive
touching;body
shield
required(n
51)
3.Abdominal
hematom
a(n
51)
4.Frequent
program-
mingrequiredinmany
Porta
etal.,
2009
58CM
-Pfc,Voa
15(12M
,3F);
*allprevi-
ously
reported6
2
17–46
7(2�18
yrs)
24mo
Case
series
IV1.
YGTSS
52%
mean
improvem
ent
1.Y-BO
CS31%
meanimprovem
ent
2.STAI
33%
meanimprovem
ent
3.BD
I26%
meanimprovem
ent
4.VASsubjectivesocial
impairm
ent
31%
meanimprovem
ent
Yes
No1.
3ptsfrom
previous
cohort(n
518)were
excluded:
2ptsrequestedremoval
ofIPGandDB
Swas
stopped
1pt
didpoorlyand
requiredsubsequent
GPi
DBS
Ackerm
ans
etal.,
2011
30
CM-Spv-Voi
8(2F,
6M);
*2Flostto
follow-up
21–48
1(21)
12mo
Double-blind
random
ized
cross-over
trial
36mo,
then
6moopen-
label
III1.
YGTSS
49%
improvem
ent
2.mRVTRS
35%
improvem
ent
1.Y-BO
CS—no
change
2.CA
ARS—
nochange
3.BD
I(Du
tch)—no
change
4.BA
I—no
change
5.VASforSIB—
nochange
Yes(1
life-
threatening,
lost
tofollow-up)
Yes
1.Decreasedenergy
lev-
els,subjectivegaze
dis-
turbance,negativeimpact
ondaily
livinginallpts
2.1sm
allhem
orrhageat
lead
tip—gaze
palsy3
6mo,
persistent
nystagmus
3.1IPGInfection
4.Severe
complications,
psychogenicsymptom
s,&
eventualdeathin1pt
lostto
follow-up(see
details
below40)
Duits
etal.,
2012
39CM
-Spv-Voi
1(F)*enrolled
butdidn’t
complete
previously
reported
trial31
211(21)
23mo
Case
report
IV1.
YGTSS—
worse
with
DBSON
:Pre-op—42
Stim
OFF—
12Stim
ON—39
1.Y-BO
CS:
Preop—
20Stim
OFF—
8Stim
ON—7
2.CA
ARS:
Pre-op—
58Stim
OFF—
42Stim
ON—45
Yes(life-
threatening)
No1.
Severe
postoperative
complications
with
psy-
chogenicparoxysm
alhypertonia,
disturbances
ofconsciousness,and
mutism
2.No
change
with
DBS
OFF
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
3.BD
I-II:
Pre-op—
12Stim
OFF—
20Stim
ON—15
4.BA
IPre-op—32
Stim
OFF—
41Stim
ON—44
5.SIB(VAS)
Pre-op—
5.7
Stim
OFF—
0Stim
ON—8.9
3.Somatoform
disorder
identified
retrospectively
4.Pt
died
ofdehydration,
refusaltoeat/drink@3
yrspostoperatively
Ackerm
ans
2007
28CM
-Spv-Voi
1(M)*previ-
ously
reported3
1
390
6mo
case
report
IVNA
None
reported
Yes(head-
banging)
No1.
Hemorrhageat
distal
electrode
tip-->
verti-
calgazepalsy:subjec-
tiveworsening
with
DBSON
Ackerm
ans
etal.,
2006
27
CM-Spv-Voi
1(M)*prev
reported7
045
01yr
Case
report
IV1.
Videotaped
ticfre-
quency
(tics/min)by
2blindedraters
85%
reduction
1.PaduaInventory—
Revised(obsession-com
-pulsionrating)
62%
betterON
than
OFF
stim
NoNo
1.Decreasedenergy
level
2.Sexualdysfunction
Vandew
alle
etal.,
1999
68
CM-Spv-Voi
1(M)
420
4mo
Case
report
IV1.
Videotaped
ticfrequency
—Nearly100%
reduction(“except
for
someexcessiveeye
blinking”)
None
reported
NoNo
Notreported
Visser-Vande-
walleet
al.,
2003
70
CM-Spv-Voi
3(3M);*1M
previously
reported2
7
28,42,45
08mo—
5yrs
Case
series
IV1.
Videotaped
ticfre-
quency
(tics/10m
in)
—72%—90%
reduction
None
reported
No(burning
eye-
lashes
with
cig-
arettes,break-
ingglassin
hands)
No1.
Reducedenergy
levels
inall3
2.Sexualdysfunctionin2
pts
3.2ptseach
required3
revisionsof
IPGand
extensionwiresdueto
tractionpain
4.1pt
hadlower
scores
ontim
edtaskson
neuro-
psychologicaltesting
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
Ackerm
ans
etal.,
2010
29
CM-Spv-Voi
2(2M);*previ-
ously
reported2
7,28
42,45
06–10
yrs
Case
reports
IV1.
Videotaped
ticfre-
quency
(tics/10m
in)
by3blindedraters
78%-92.6%
reduction
None
reported
No(breakingglass
inhands)
No1.
Reducedenergy
levels
inboth
pts
2.Both
with
hardware-
relatedcomplications
(tractionof
lead
inneck)
requiring
multiplesurgical
revisionsandlocalinjec-
tions
(previously
described
63)
3.Mild
visual
side
effects(vertigo,
blurry
vison)
inboth
4.Sexualdysfunctionin
both
5.Increasedaggression,
socialadaptationin1pt.
Maciunas
etal.,
2007
49
CM-Pf
5(4M,1F)
18–34
�1
4mo
Prospective
double-blind
crossovertrial;
four
7-d
random
ized
DBSconditions
R/L,
ON/OFF,
andopen-label
4-mofollow-up
III1.
mRVTRS
40%-67%
meanmotor
ticreduction
21%-70%
meanvocaltic
reduction
2.YGTSS
43.6%
mean
improvem
ent
2nonresponders
with
4.3–260.9%
ticexacerbation
3.TSSL
43%
meanreduction
1.SF-36(19%
mean
improvem
ent)
2.VAS(53%
meanimprovem
ent)
3.BD
I-2*(60%
meanimprovem
ent)
4.HA
M-D*(29%
meanimprovem
ent)
5.HA
M-A*(51%
meanimprovem
ent)
6.Y-BO
CS*(44%
meanimprovem
ent)
*Trend
toward
improvem
entat
4mo
Notreported
Yes(onlymean
coordinates
provided)
1.1pt
hadacutepsycho-
sison
day28
ofrandom
ized
phase—
thoughtto
berelatedto
acutelifestressors
Bajwaet
al.,
2007
31CM
-Spv-Voi
1(M)
480
2yrs
Case
report
IV1.YGTSS
63.6%
improvem
ent
1.Y-BO
CS72.4%
improvem
ent
2.CG
I“verymuchimproved”
Yes(head-snap-
ping
ticscaus-
ingcervical
myelopathy)
No1.
Although
ticsdram
ati-
cally
reduced,
the
head-snappingticshad
onlymild
reductionin
forcefulness
andhe
hadcontinuedneuro-
logicaldeterioration
dueto
myelopathy
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
Shieldset
al.,
2008
67CM
*(ALIC
leadsprevi-
ously
removed)
1(F)
400
3mo
Case
report
IV1.
YGTSS
46%
improvem
ent
None
reported
Yes(head-snap-
ping
tics,lim
bfractures,
retinal
detachment)
No1.
High
stimulationset-
tings
requiredcausing
IPGdepletionq1–2
yrs
Savica
etal.,
2012
60CM
-Pf
3(2M,1F)
17–35
2(17,17)
1yr
Case
series
IV1.
YGTSS
70%
mean
improvem
ent
None
reported
Yes(jaw-
clenchingcaus-
ingdentalfrac-
tures;head-
snapping
tics)
No1.
Mild
stimulation-related
adverseeffectsam
ena-
bleto
programming
changes.
Idris
etal.,
2010
43CM
-Pf,Voa
1(M)
241
2mo
Case
report
IVNo
scales
reported
(tics
notedto
improve)
None
reported
NoNo
1.Postoperativebilateral
subcorticalhematom
asattributedto
lowfactor
XIIIA
Marceglia
etal.,
2010
50
CM-Pf,Voa
7(6M,1F)
*many/all
reported
elsewhere
(62)
24–52
1(24)
6mo-2yr
Case
series
IV1.
YGTSS
33%
meanimprove-
ment(10%
-49%
)
1.Y-BO
CS(3%
mean
improvem
ent;24%
improvem
entto
47%
worsening)
2.BD
I(7%
meanimprovem
ent)
3.STAI
(20%
meanimprovem
ent)
4.10-ptVAS
ofsocial
integration(14%
mean
improvem
ent
Notreported
NoNotreported
Servelloet
al.,
2010
63CM
-Pfc,Voa
(1unilateral,
excluded
from
analysis)
31(25M
,6F,);
*�18
previ-
ously
reported(62)
(4additional
ptsreceived
leadsin
multipletar-
gets&1in
ALIC/NA
only)
17–57
113mo-4yr
Case
series(36pt
cohort;
6excluded
from
analysisdueto
<3mof/u
ornon-thalam
ictarget)
IV1.
YGTSS
47%
meanimprove-
mentat
lastf/u
(p<
0.001)
1.Y-BO
CS17.3%
improvem
entat
lastf/u
(p5
.017)
2.BD
I32.4%
improvem
entat
lastf/u
(p<
0.001)
3.STAI
31.7%
improvem
entat
lastf/u
(p<
0.002)
4.10-ptVAS
ofsocial
integration
30.7%
improvem
entat
lastf/u
(p<
0.001)
Yes(2
with
cervi-
calm
yelopathy,
1with
col-
lapsed
trachea,
from
tics)
No1.
Infectionof
IPG/exten-
sionsrequiring
system
removal(n
51)
2.Infection
ofIPG
site
requiring
revision
(n5
2)3.
Wound
revision
along
lead
extensions
dueto
pickingbehavior
(n5
2)4.
Lead
revision
32in
1patient
5.Ruptureof
lead
exten-
sion
(n5
1)6.
IPGremoved
@27
mo
atpt
requestd
uetounsat-
isfactoryresults
1aes-
theticconcerns
(n5
1)
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
7.DB
Sturned
offat
patient
request(n
52;
after2mo[excludedfrom
analysis]and2yr)
Porta
etal.,
2012
59CM
-Pfc,Voa
18(3F,
15M);
*previously
reported(62)
17–47
85–6yrs
Case
series
IV1.
YGTSS
73%
meanimprove-
ments(p
<0.001)
2.GC
I—ratings
variedbetweenpro-
viders
andbetween
provider
andpatients
1.Y-BO
CS42%
meanimprovem
ent
(p5
0.003)
(4pts
worsened)
2.STAI
46%
meanimprovem
ents
(p<
0.001)
3.BD
I55%
meanimprovem
ent
(p<
0.001)
Yes
No1.
Poor
wound
healing
dueto
patient
picking(n
51) 2.
Abdominal
wall
hematom
a3.
2ptsrequestedDB
Sturned
off@
3–4yrsfor
personalreasons
4.1pt
toldto
have
DBS
removed
dueto
repeated
infections
despite
improvem
entof
tics
5.Issues
with
noncom
pli-
ance
insomepatients
Kuhn
etal.,
2011
46Vop-Voa-Voi
(Unilateral)
227
(F);39
(M)
012
mo
Case
series
IV1.
YGTSS
75%-100%
improvem
ent
2.MRVRS
77%-100%
improvem
ent
1.BD
I-2—No
negative
impact
2.GA
F—Both
hadcontin-
uous
improvem
ent(52%
-73%)during12
mo
NoNo
1.Reducedverbalfluency
@1yr
inboth
pts
(�25%
worsening)
Leeet
al.,
2011
48CM
-Pf
131
(M)
018
mo
Case
report
IV1.
YGTSS
62%
improvem
ent@
6mo(sustained
at18
mo) 2.MRVRS
38%
improvem
ent
3.VAS
70%
improvem
ent
None
reported
Yes
No1.
None
reported;
pro-
gram
mingwas
reportedto
bedifficult
Okun
etal.,
2012
55CM
(scheduled
stimulation)
5(3F,
2M)
28–39
06mo
NIH-sponsored
clinicaltrials
planning
study
ofsafetyand
preliminaryeffi-
cacy;delayed
startactivation
(30d)
III1.
YGTSS
19%
mean
improvem
ent(p
5
0.01;5%
-30%
)2.
mRVTRS
36%
meanimprove-
ment(p
50.01)
1.Y-BO
CS2.
HDRS
3.YM
RS(Young
Mania
RatingScale
4.SF-36
5.QO
LAS
*Noneof
thesemeasures
improved,although
atrend
towardimproved
physicalfunctioning
inboth
QOLmeasures
Yes(3
of5pts)
Yes
1.No
major
adverse
events
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
Kuhn
etal.,
2012
47Thalam
us,pal-
lidal,&nig-
ralinput
areas(uni-
lateralin1)
3(2M,1F);*2
previously
reported4
7,69
22–27
2(22,22)
NACase
series
IV1.
YGTSS
36%-83%
improvem
ent
None
reported
Notreported
Yes
None
reported
Vernaleken
etal.,
2009
69
Pf-DM-LM
1(M)
221
NACase
report
IV1.
YGTSS
36%
improvem
ent
None
reported
Notreported
Yes
1.Patient
hadpreviously
undergonebilateralG
PiDB
Swithout
improvem
ent
Servelloet
al.,
2011
64NA
39;*mostpre-
viously
reported(64)NA
NARetrospective
review
IVNotreported
Notreported
Notreported
Notreported
1.Lead
fracturedueto
head-snappingtics
2.18%
incidenceof
infectious
complications
(7patients),requiring
sur-
gicalrevision
3.All7
patientswith
infections
hadrecurrent
infection
4.Infections
thought
relatedto
compulsive
touching
ofsurgicalscars
Kaidoet
al.,
2011
44CM
-Pfc
3(1M,2F)
19–21
3(20,21,19)
12mo
Case
series
IV1.
YGTSS—
39.1%
mean
improvem
ent
1.Y-BO
CS—slight
decrease
in2pts,
increase
in1pt
2.BD
I-II—
variedbetween
patients
3.IQ—no
significant
meanchange
Yes(2
of3pts)
Notreported
1.Temporary
blurred
vision
with
increased
stimulationam
plitude
Motlagh
etal.,
2013
53Midline
thalam
ic4M
16–44
2(16,17)
6–95
mo
Case
series
IV1.
YGTSS—
dram
atic
improvem
ent
inthe2youngpts
(67%
-85%
);lim
itedimprove-
mentintheolder
pts(7%-20%
)
1.Y-BO
CS—100%
improvem
entin1pt;
minimalchange
orwor-
sening
intheothers
2.HD
RSandHA
RS—no
significant
change
Yes(2
of4pts)
Yes
1.44-yoM
hadcompul-
sive
pickingat
chestand
cranialincisions;DB
Ssystem
removed
because
ofinfection
2.42-yoM
hadDB
Ssys-
tem
removed
becauseof
lack
oftherapeutic
benefit
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
Target:P
allidal
Diederich
etal.,
2005
36
pvGP
i1
27(M)
014
mo
Case
report
IV1.
Videotaped
ticfrequency
(tic/min)
85%
reduction
(66%
ticincrease
with
DBSOFF)
2.YGTSS
47.0%
improvem
ent
1.BD
I(75%
improvem
ent)
2.STAI
(30%
improvem
ent)
3.SR
SI-90-R
(31%
-61%
improvem
ent)
NoNo
1.Perm
anentleft-sided
bradykinesia(grade
2–3
onUPDR
S)—toleratedby
pt;reducedmildlywith
stimulationOFF3
48hr
2.Sm
allnon–m
ass-
occupyinghematom
a@
tipof
Relectrode
onpost-opMRI
3.Transientmild
fatigue
forseveralm
onths
Shahed
etal.,
2007
65pvGP
i1(M)*also
reported
(66)
161
6mo
Case
report
IV1.
YGTSS
84%
improvem
ent
2.TSSR
88%
improvem
ent
3.mRVTRS
21%
improvem
ent
1.Children’sY-BO
CS(69%
improvem
ent)
2.SF-36v2
(65%
improvem
ent)
3.BA
SC-2
(improvem
entsinseveral
domains,includinghyper-
activity,aggression,anxi-
ety,depression,
somatization)
NoNo
1.Patient
compulsively
pushed
onIPGs,requir-
ingbody
shieldfor4
wks
Shahed
etal.,
2007
66pvGP
i3
3M(16–35)
2(16,16)
3–12
mo
Case
series
IV1.
YGTSS
35%-76%
improvem
ent
2.TSSR
16%-90%
improvem
ent
3.RVTRS
17%-50%
improvem
ent
4.Ticfrequency
(tics/min)
37%-69%
reduction
1.Y-BO
CS(22%
-69%
improvem
ent)
Notreported
No1.
Nosurgicaladverse
events.
2.1patient
compulsively
pushed
ontheIPGsite.
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
Dehninget
al.,
2008
34pvGP
i1
44(F)
012
mo
Case
report
IV1.
YGTSS
88%
improvem
ent;
noremaining
tics
None
reported
No(self-biting,
beating)
Yes
1.Frequent
visitsin1st
fewmonthsfordepres-
sion,vertigo,stom
ach
aches;difficulty
adjust-
ingto
newsituation
withouttics.
Dehninget
al.,
2011
35pvGP
i4;
*1previ-
ously
reported(35)3F
(25–44);
1M(38)
05–13
mo
Case
series
IV1.
YGTSS
6%worsening
to88%
improvem
ent
2.CG
I67%
meanimprove-
ment(including2with
nochange)
3.TSGS
12%
worsening
to80%
improvem
ent
(mean37%)
None
reported
Yes(burning
ofskinwith
iron)
No1.
Stimulationstopped
dueto
lack
ofresponse
(n5
2)2.
Lead
revision
toa
moreposteriorlocation
was
done
in1nonres-
ponder,without
improvem
ent
Dong
etal.,
2012
37pvGP
i(unilat-
eralR)
22M
(22,
41)
1(22)
1year
Case
report
IV1.
YGTSS
53%-59%
22reductionNo
nereported
NoNo
1.No
severe
adverse
effects
Dueck2009
38pvGP
i1
16(M)
1(16)
1year
Case
report
IV1.YGTSS(adapted
for
children;
inGer-
man)—
nosignifi-
cant
improvem
ent
Reportedno
associated
psychiatric
symptom
sNo
Yes
Notreported
Gallagher
2006
41pvGP
i1
26(M)
0NA
Case
report
IV“Disappearance
ofvocalticsand
markedimprove-
mentsinneck
movem
ents”
NANone
reported
NoNotreported
Martinez-Fer-
nandez
2011
52
pvGP
i(3);
amGP
i(3)
54M
(21–60);1F
(35)
1(21)
3–24
mo
Case
series
IV1.
YGTSS
29%
mean
improvem
ent
2.mRVTRS
45%
mean
improvem
ent
Impression:am
GPiis
superiorto
pvGP
i(YGTSS
38%
vs.20%
improvem
ent;
mRVTRS54%
vs.
37%)
1.Y-BO
CS(26%
mean
reduction)
2.GTS-QO
L(55%
mean
improvem
ent;availablein
3pts)
3.GTS-QO
LVAS—
40pointsmeanimprovem
ent
(total1
00)
Yes(2
with
cervical
myelopathy
from
head-
snapping
tics)
No1.
Twoinfections
in1
patient
(requiring
system
removal3
1,IPG/exten-
sionsremoval3
1)2.
Lethargy,agitation,
anxiety;unhappywith
results
despite
reduced
tics(n
51)
3.Low
thresholdcapsu-
larside
effects;lead
revi-
sion
toanteromedial
target,then
anxietywith
>100Hz
stimulation
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
4.Acutedeteriorationin
ticswith
transient
stim
OFF—
only70%
ofprevi-
ouscontrolafterback
ON5.
Weightgain(n
51)
Cannon
etal.,
2012
33am
GPi
118M
(22–50);3F
(18–34)
2(18,22)
4–30
mo
Case
series
IV1.
YGTSS
50%
mean
reduction@
3mo
1.Y-BO
CS(59%
mean
improvem
ent)
2.HD
RS(74%
meanimprovem
ent)
3.GTS-QLS—
significant
improvem
ent(102%
meanimprovem
ent)
4.GA
F(57%
meanimprovem
ent)
Yes(requiring
24-
hrmonitoringto
preventhead
injury)
No1.
Onept
didnottolerate
DBSandturned
OFFafter
3mobecauseof
somatic
complaints
2.Hardwaremalfunction
(lead
fracture)
in3pts
(because
of:SIBtic,MVA,
unknow
n)3.
Lead
infectionrequir-
ingbilateralleadreplace-
ment(n
51)
4.Increasedanxietyin
2pts(1
transient,1persis-
tent,&fluctuating)
Filhoet
al.,
2007
56GP
e1
NANA
23mo
Case
report
(abstract
only)
IV1.
YGTSS—
81%
reduction
1.Y-BO
CS—84%
reduction
Notreported
NoNotreported
Piedimonte
etal.,
2013
57
GPe
147
(M)
02yrs
Case
report
IV1.
YGTSS
71%
improvem
ent@
6mo
significant
worsening
@2yr
whenIPGbat-
tery
died
1.Y-BO
CS(noOC
Dpre-
orpost-op)
2.HD
RS(82%
improvem
ent@
6mo)
3.HA
RS(75%
improvem
ent@
6mo)
4.GA
F—(36%
improvem
ent@
6mo)
NoNo
Notreported
Motlagh
etal.,
2013
53pvGP
i2
2M(24,
42)
1(24)
8–51
mo
Case
series
IV1.
YGTSS—
20%-44%
improvem
ent
1.Y-BO
CS—no
significant
change
2.HD
RS—no
change
tomild
improvem
ent
3.HA
RS—slight
improvem
ent
Yes(2
of2;
punching
self,
neck-snapping
tics1
cervical
spineinjury)
Yes
1.Lead
extender
revision
dueto
post-auricular
dis-
comfort,
possibleIPG
malfunctionwith
revision
toabdominalplacem
ent
2.Stimulation-induced
side
effects:hyperkinetic
leftarm
movem
ent,right
foot
cram
ping,flashingin
eyes,restlessness;Left
lead
quite
medial (Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
Target:M
ultiple
Targets
Servelloet
al.,
2009
62CM
-Pfc,Voa
1ALIC/NA
(n5
1);
CM-Pfc,Voa
1ALIC/NA
add-on
(n5
2)
3;*Also
reported6
225–37(2M,
1F)
019–44moCase
series
(partof
4pt
cohort)
IV1.
YGTSS
2ptshad
modestreductionin
tics(23%
-34%
)afterinitialCM
-Pfc,VoaDB
Sbut
depression/OCD
remaineddisabling
83%
reductioninpt
with
simultaneous
CM-Pfc,Voa1
ALIC/NA
1.BD
I2.
STAI
3.YBOC
S4.
VASof
social
integration
2ptswith
“rescue”
ALIC/NAleadshadonly
mild
improvem
enton
thesemeasures
ptwith
simultaneousCM
-Pfc,Voa1
ALIC/NAdid
have
significant
improve-
ment(45%
,39%,61%,
35%,respectively)
Yes(1
cutself
with
knife,1
punchedselfin
head)
No1.
None
reported
2.ALIC/NArescue
leads
werenotvery
effective
Servelloet
al.,
2010
63pGPi
1ALIC/
NAadd-on
142
(F)
0pGPi:23
mo;
GPi
1ALIC/
NA
Case
series
(partof
36pt
cohort)
IV1.
YGTSS
14%
improvem
ent
@23
mowith
pGPi
41%
further
improvem
entafter
ALIC/NA(49%
total)
1.Y-BO
CS(26%
reductionwith
GPi;
16%
further
after
ALIC/NA)
2.STAI
(23%
improve-
mentwith
GPI;12%
fur-
ther
afterALIC/NA)
3.BD
I(5%
improvem
ent
with
GPi;30%
further
afterALIC/NA)
4.VASof
social
integra-
tion(15%
improvem
ent
with
GPi;12%
further
afterALIC/NA)
Notreported
forthiscase
No1.
Required“rescue”
ALIC/NAleadsbecause
ofsocialimpairm
ent
andpoor
QOLdespite
reductioninticswith
GPiD
BS
Ackerm
ans
etal.,
2006
27
pvGP
i1CM
-Spv-Voi
(*onlyGP
iactivated)
127
(M)
01yr
Case
report
(partof
2pt
series)
IV1.
Videotaped
exam
with
ticfrequency
(tics/min)by
2blindedraters
;93%
reduction
1.PI-R
forcompulsive
symptom
s—notedto
have
“totalresolution”
NoNo
1.Reducedenergy
level
2.Briefdystonicjerk
each
timeturned
ON
Welteret
al.,
2008
71CM
-Pf1
GPi
(limbic)
3;*1
previ-
ously
reported(43)2F
(36,
30);
1M(30)
020–60
mo
Controlled,
double-blind,
random
ized
crossover
study1
open
long-term
f/u
III1.
YGTSS
(cross-overperiod)
a)GP
i):65%-96%
improvem
ent
b)CM
-Pf
None
reported
Yes(eye
mutilation,
burningof
skin)
No1.
Thalam
ic—decreased
libidoin1pt
2.GP
i—lethargy
(3–4
d);
nausea
&vertigo
athigher
settings(n
52);
anxiety(n
51)
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
30%-64%
improvem
ent
c)GP
i1CM
-Pf
43%-76%
improvem
ent
2.YGTSS(long-term
f/u)
CM-Pf/G
PiON
(n5
2;74%-82%
improvem
ent)
GPiON
(n5
1;mild
improvem
ent)
3.RVTRS
Houeto
etal.,
2005
42
CM-Pf1
GPi
(limbic)
136
(F)
011
mo
Prospective
double-blind
random
ized
N5
1crossover
trial
III1.
YGTSS
CM-Pf:64%
reduction
GPi:65%
reduction
“Sham”STIM:worse
than
baseline
CM-Pf1
GPi:34
(60%
reduction)
2.RVTRS
CM-Pf:77%
reduction
GPi:54%
reduction
“Sham”STIM:15%
reduction
CM-Pf1
GPi:77%
reduction
1.MAD
RS2.
BAS(anxiety)
3.BIS(im
pulsivity)
SUMMAR
Y:CM
-Pf:mood&
impulsivity
improved:SIB
resolved
GPi:mood&impulsivity
worse
than
CM-Pf;SIB
resolved
SHAM
:little
change
ofdepression/anxiety
CM-Pf1
GPi:SIB
resolved
Yes(eye
mutila-
tion,
burningof
skin)
No1.
Weightloss
(18kg
with
CM-Pf,continued
with
GPi)—
may
have
been
relatedto
with-
draw
alof
neuroleptics
2.Du
ringSH
AMstim:
SIB,
excoriations
atcables
Shields
etal.,
2008
67
ALIC/NA(*later
revisedto
CMDB
S)
140
(F)
018
mo
Case
report
IV1.
YGTSS
23%
improvem
ent
None
reported
Yes(head-snap-
ping
tics,lim
bfractures,retinal
detachment)
No1.
Lead
extensionfracture
dueto
residualhead-
snapping
ticsafterALIC/
NADB
S2.
Stimulation-induced
alteredmoodandimpulse
controlproblem
s2
48,19
(2M)
1(19)
Case
series
IV1.
YGTSS
Yes
1.48yoM:
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
Motlagh
etal.,
2013
53
1.Midlinetha-
lamic1
pvGP
i2.
amGP
i1midlinetha-
lamic1
GPi-
pv
37–107
mo
19yo
with
3targetshadno
improvem
ent
48yo
had72%
improvem
ent
1.Y-BO
CS–48yo
had
significant
improvem
ent
(29-->
8);19yo
hadno
OCB
2.HD
RS–both
hadwor-
sening
ofdepression
3.HA
RS–no
change
Yes(2
of2;
slam
-mingforearm
againsthead,
head-snapping
tics1
cervical
injury;poking
lefteye,
left
cheekbiting)
2ndtarget
addeddueto
continuedhead-snapping
tics
GPileadextender
mal-
functiondueto
head-
snapping
tics
thalam
icandGP
ileads
nowOFF
2.19yoM:
ICU
hospitalization
with
sedationforworsening
tics2m
oafteram
GPi
placem
entto
preventeye
injury
3separate
DBSsurgeries
for3totalbilateraltargets
dueto
refractorytics;cur-
rentlyhasonlyRpvGP
ilead
onandno
improvem
ent
OtherTargets:ALIC/NA,
STN
Kuhn
etal.,
2007
45ALIC/NA
126
(M)
030
mo
Case
report
IV1.
YGTSS
41%
improvem
ent
2.mRVTRS
50%
improvem
ent
1.Y-BO
CS(52%
improvem
ent)
2.GA
F—significantly
improved
(7->
41)
Yes
No1.
High
stim
requirements
(2IPGreplacem
entsin30
mo) 2.
Temporary
deteriora-
tioninsymptom
swith
battery
depletion3
2Flaherty
etal.,
2005
40
ALIC/NA
137
(F)
018
mo
Case
report
IV1.
YGTSS
25%
improvem
ent\
2.Patient
ticlogs
45%
decrease
infrequency
and
severity
None
reported
Yes(head-snap-
ping
tics,lim
bfracture,
retinal
detachments)
No1.
Stim-induceddysarth-
ria,rhythm
icjaw
clenching
2.High-voltage
stim
inventralcontacts(near
NA)—
mild
apathy
and
depression;dorsalcon-
tactsinbody
ofcap-
sule—agitatedhypomania
(hrs
todays
onsetfor
moodeffects)
(Continued)
TABLE1.Continued
Target:Thalamic
Study
Target
Sample
size
(n)
AgeatDBS
(years)
Subjects
<25
yrs
(ages)
Follo
w-up
Study
Design
Levelof
Evidence
Tic
Outcome
Measures
Comorbidity
OutcomeMeasures
SIB
WithIm
medi-
ate
RiskofBodily
Harm
(Yes/N
o)
Postoperative
LeadLocation
Reported(AC-P
C
Coordinates)
AdverseEvents
Reported
3.IPGaccidentallyturned
offseveraltimes—symp-
tom
worsening
4.Fracturedlead
exten-
sion
requiring
replace-
ment—
dueto
tics
Zabek
etal.,
2008
72
ALIC/NA(uni-
lateralR
)1
31(M)
028
mo
Case
report
IV1.
15-m
invideotaped
exam
swith
ticcounts
80%
improvem
ent
None
reported
Yes(retinal
detachment,
blindness)
No1.
IPGmalfunctionat
9monthsdueto
RUE
motor
tics!
sxdeteri-
oration!
improve-
mentafterIPGreplaced
Neuner
etal.,
2009
54
ALIC/NA
138
(M)
036
mo
Case
report
IV1.
YGTSS
44%
improvem
ent
2.mRVTRS
58%
improvem
ents
1.Y-BO
CS(56%
reduction)
Yes(self-mutila-
tion;
breaking
glassinhands)
No1.
RapidIPGdepletion—
2IPGreplacem
entsin36
months
Burdick
etal.,
2010
32
ALIC/NA
133
(M)
030
mo
Case
report
IV1.
YGTSS
15%
worse
in1st6
mo
2.mRVTRS
Tics
20%
worse
@30
mo(5->
6)
1.Y-BO
CS(nosignificant
improvem
ent)
NoYes
Notreported
Martinez-
Torres
etal.,
2009
51
STN
138
(M)
01yr
Case
report
IV1.
RVTRS
97%
improvem
ent
1.UPDR
S(pthadPD
;57%
improvem
ent)
NoNo
Notreported
Servello
etal.,
2009
62
ALIC/NA
1;*Previously
reported(64)47
(M)
010
mo
Case
series(part
of4pt
cohort)
IV1.
YGTSS
79%
improvem
ent
1.Y-BO
CS(54%
improvem
ent)
2.BD
I(9%
improve-
ment;notsignificant)
3.STAI
(19%
improve-
ment;notsignificant)
4.10-ptVAS
ofsocial
integration(nochange)
NoNo
None
reported
BAS,BriefAnxiety
Scale;BIS,Barratt’s
ImpulsivityScale;CM-P
fc,Voa,centromediannucleus-parafascicular,andventro-oralis
complex;CM-S
pv-Voi,centromediannucleus-substantiaperiventricularis-nucleusventro-oralis
internus
complex;CM-P
f,centromediannucleus–parafascicularcomplex;Vop-Voa-Voi5
nucleusventro-oralis
posterior,ventro-oralis
anterior,andventro-oralis
internuscomplex;Pf-DM-LM,parafascicular,dorsomedialnucleus,andlamella
medialis;CM,centromediannucleusregion;GPi,globuspallidusinternus;pvGPi,posteroventralglobuspallidusinternus;amGPi,anteromedialglobuspallidusinternus;YGTSS,Yale
GlobalTic
Severity
RatingScale;Y-B
OCS,Yale-
BrownObsessiveCompulsiveScale;BDI,BeckDepressionInventory;BDI-2,BeckDepressionInventory,2ndEd.;HARS,HamiltonAnxiety
RatingScale;HDRS,HamiltonDepressionRatingScale;STA
I,State-TraitAnxiety
Inventory;
AC-P
C,anteriorcommissure–posteriorcommissure;mRVTRS,modifiedRushVideo-basedTic
RatingScale;RVTRS,RushVideo-based
Tic
RatingScale;CAARS,Conners
AdultADHD
RatingScale;PDD-S
Q,PervasiveDevelop-
mentalDisorder-SelfQuestionnaire;TSSL,To
uretteSyndromeSymptom
List;YMRS,YoungMania
RatingScale;QOLAS
5QualityofLifeAssessmentSchedule;SRSI-90-R
,Self-report
symptom
inventory
90Items—revised;TSSR
5Tic
Symptom
SelfReport;BASC-2,BehaviorAssessmentSystem
forChild
ren—2ndEd;TSGS,To
uretteSyndromeGlobalScale;PI-R,5
PaduaInventory
ofobsessivecompulsivedisordersymptoms—Revised.
develop recommendations, and these were publishedin 2006.7 Subsequently, a collaborative internationalnetwork of investigators was established, and in 2010to 2011 the TSA commissioned an International Data-base/Registry of DBS outcomes and cases performedin patients with a diagnosis of TS. The purpose of thispaper is to critically review the literature of all pub-lished cases of TS DBS and to provide updated opin-ions and recommendations for patient selection andassessment since 2006.7 Additionally, we aimed toencourage all clinicians and investigators who care forTS DBS patients to participate in the TSA DBS Data-base/Registry to collect more data and to enhance theunderstanding of surgical approaches and outcomes.Since 1999, 48 TS DBS studies have been published,
including approximately 120 patients from 23 centersin 13 countries. At least seven separate brain targetshave been employed27-72 (Table 1). The most com-monly used targets have been the medial thalamicregion targets (eg, centromedian nucleus–parafascicu-lar complex [CM-Pf]), with 70 reported cases. Thirty-one cases of pallidal TS DBS have been reported andhave included both anteromedial globus pallidus inter-nus (GPi; “limbic”) targets (n 5 14) and posteroven-
tral GPi targets (n 5 16). One case report of globuspallidus externa (GPe) DBS has also been published.The anterior limb of the internal capsule/nucleusaccumbens target in isolation has been used in six casereports, and one case of STN DBS has been reportedin a patient who had both tics and Parkinson’sdisease.Eleven reported cases have employed more than one
brain target (2 targets in 10 cases, and 1 case with 3brain targets). In most of these cases, however, theadditional target leads were added as “rescue” leadsbecause of inadequate response to the initial TS DBSleads. Three cases reported were part of a prospective,double-blind, randomized crossover study comparingthe CM-Pf and the anteromedial GPi targets.42,71
Although nearly all studies reported a beneficialeffect on tics, most of these reports were uncontrolledcases (n 5 100), and the results revealed wide varia-tions in study methods and outcomes, thus limitingmeaningful interpretation. Approximately one fifth ofthe papers did not report using a validated outcomeor videotape analysis. Rating scales to capture TScomorbidities (eg, obsessive-compulsive behavior, anx-iety) were used in fewer than one third of reported
TABLE 2. Updates to 2006 TS DBS Guidelines
2006 Guidelines Revised Guidelines
Diagnosis DSM-IV diagnosis of TS by expert clinician DSM-V diagnosis of TS by expert clinicianAgea �25 yrs 1. Age is not a strict criterion
2. Local ethics committee involvement for cases <18 years old
Tic severity 1.Severe tic disorder with functional impairment2. YGTSS > 35/503. Document with standardized video assessment
1. Severe tic disorder with functional impairment2. YGTSS > 35/503. Document with standardized video assessment
Neuropsychiatric comorbidities(ie, ADHD, OCB, depression, anxiety, etc.)
1. Tics should be the major symptom causingdisability2. Comorbid conditions should be stably treated3. Comorbid conditions should be assessed usingvalid rating scales when available
1. Tics should be the major symptom causingdisability2. Comorbid conditions should be stably treated3. Comorbid conditions should be assessed usingvalid rating scales when available
Failed conventional therapya 1. Failed treatment trials from 3 pharmacologicalclasses: a) alpha-adrenergic agonist, b) 2 dopamineagonists (typical & atypical), c) benzodiazepine2. Evaluated for suitability of behavioral interventionsfor tics
1. Failed treatment trials from 3 pharmacologicalclasses: a) alpha-adrenergic agonist, b) 2 dopamineagonists (typical & atypical), c) a drug from at leastone additional class (eg, clonazepam, tetrabenazine)2. A trial of CBIT should be offered
Comorbid medical disorders Stable for 6 months before DBS Stable for 6 months before DBSPsychosocial factors a 1. Adequate social support without acute or suba-
cute psychosocial stressors2. Active involvement with psychological interven-tions when necessary
1. Adequate social support without acute or suba-cute psychosocial stressors2. Active involvement with psychological interven-tions when necessary3. Caregiver available to accompany patient for fre-quent follow-up4. Psychogenic tics, embellishment, factitious symp-toms, personality disorders, and malingering mustbe recognized and addressed
Suicidal/homicidal ideation (SI/HI) a Not specifically addressed Documentation of no active SI/HI for 6 months
aRecommendations have changed since 2006.TS, Tourette syndrome; DBS, deep brain stimulation; DSM, Diagnostic and Statistical Manual of Mental Disorders; YGTSS, Yale Global Tic Severity Scale;ADHD, attention deficit hyperactivity disorder; OCB, obsessive compulsive behaviors; CBIT, cognitive behavioral intervention therapy.
S C H R O C K E T A L
16 Movement Disorders, Vol. 00, No. 00, 2014
studies, and postoperative DBS lead locations werereported in only 10 of 50 studies.Based on the levels of evidence classification scheme
that has been used by the American Academy of Neu-rology,73 only four of these 48 studies30,49,55,71 metcriteria for class III level of evidence (n 5 19),whereas the others were class IV. Given the smallnumber of patients and the use of multiple brain tar-gets within the class III studies, these data wouldlikely receive the lowest evidence rating (level U), indi-cating that the therapy remains unproven because ofinadequate or conflicting data.Since the last TSA guidelines were published in
2006,7 the field has gained important insight aboutsafety and the potential for specific adverse effects ofTS DBS. Thirty-three patients had TS DBS before theage of 25 years, including nine patients younger than18. The risk of surgical complications and adverseevents did not appear to be higher in these age groupswhen compared with patients older than 25 years.However, Servello et al.,61 in their series of 18patients who underwent bilateral CM-Pf DBS, cau-tioned that three of the four cases who were implantedbefore the age of 20 years had less than satisfactoryresults after 3 to 6 months of follow-up (significantspontaneous waxing and waning of symptoms requir-ing frequent DBS programming).Ackermans et al.30 reported substantial improve-
ment in six patients on the Yale Global Tic SeverityScale (YGTSS) between the ON and OFF stimulationconditions (37%), and also improvement after 6months of open-label therapy (49%) in a double-blindrandomized cross-over trial of centromedian nucleus–substantia periventricularis–nucleus ventro-oralis inter-nus (CM-Spv-Vo) DBS. Significant adverse effectswere reported, including decreased energy levels aswell as subjective gaze disturbances. One patient withcomorbid depression, pervasive developmental disor-der, compulsions, and severe self-injurious behavior(SIB) had surgery under the condition of clinicalurgency and had to be withdrawn from the trialbecause of severe postoperative complications withpsychogenic paroxysmal hypertonia, disturbances ofconsciousness, and mutism. Somatoform disorder inthis patient was only recognized retrospectively, andthe patient eventually died of dehydration after refus-ing intravenous fluids.39
Servello et al.64 has reported the most robust experi-ence with TS DBS, and also published an importantpaper analyzing the rates of infectious and hardware-related complications for different DBS indications(eg, PD, TS, tremor, and dystonia). Servello’s groupreported an increased risk of infectious complicationsin TS DBS (7 of 39 [18%] patients) compared with anoverall infection rate for all DBS indications of 3.7%(10 of 272 patients). The TS DBS patients also may be
at increased risk for hardware malfunction. Six casesof lead or lead extension fractures, or alternativelyIPG malfunction, have been reported,33,40,53,67,72 fourof which were attributed to residual head-snappingtics. These findings highlight the unique and poten-tially severe issues in the TS population. Whereas ticsthat are life threatening or carry significant risk ofimmediate bodily harm are observed in only 5.1% ofall TS patients, nearly 50 TS DBS cases with signifi-cant SIB have been reported in the literature, withmore than half of these cases involving a severe behav-ior or risk of severe bodily harm (eg, cervical myelop-athy from head-snapping tics, bone fractures, retinaldetachment).Although few data are available to guide postopera-
tive management of TS DBS patients, Servello et al.have the greatest experience with TS DBS to date.These authors have reported that TS DBS patientsrequire more frequent visits for DBS adjustments (ie,in excess of monthly visits stipulated in their protocol)than for other DBS indications, and also TS DBSpatients require substantial personal and family sup-port. For this reason, a thorough evaluation of thepatient’s adherence to recommendations, a clearassessment of the patient’s psychosocial situationinclusive of family dynamics, and the need for realisticpatient and family expectations should beemphasized.58,61,63
Given the dearth of double-blind controlled studiesof TS DBS, the lack of consistent outcome measuresrelated to TS comorbidities, and the lack of rigorousstudies comparing brain targets, few data are availableto guide target choice either in general or in specificpatients.Chronic continuous stimulation has been widely
assumed to be the only effective approach to TS DBS.Recently, however, this notion has been challenged byOkun et al.,55 who demonstrated the potential of non-continuous DBS paradigms in TS in a class III clinicaltrial planning study (n 5 5) of safety and preliminaryeffectiveness.55 Additionally, these authors have sug-gested that responsive approaches may be possible,especially by using oscillations (eg, the gamma band)and other brain network oscillations associated withDBS efficacy.74
Special Considerations Relevant toTS DBS and Guideline Updates
The official DSM V diagnostic criteria require thepresence of tics for more than a year, with onsetbefore the age of 18 years, and occurrence of bothmultiple motor and at least one phonic tic for a defini-tive diagnosis of TS.1 The variability (variability of tictypes, as well as the waxing and waning of tic sever-ity) in TS provides an extra level of complexity when
T O U R E T T E S Y N D R O M E D B S G U I D E L I N E S
Movement Disorders, Vol. 00, No. 00, 2014 17
considering TS candidates for DBS therapy. Tics canbe influenced by both environmental and psychologi-cal factors. Many TS patients can suppress tics par-tially or even completely for short periods, such aswhen being examined or when in public, but thenrelease tics when returning to a more comfortable set-ting. The recognition of embellishment, psychogenictics, factitious symptoms, personality disorders, andmalingering all need to be considered in the preopera-tive workup,39,75-77 similar to the experience in epi-lepsy surgery with nonepileptic events.78
A clinician with expertise and experience with TSpatients should confirm the diagnosis by strict criteria1
and address all psychological comorbidities and non-motor features before consideration of DBS. Patient-or family-expressed psychological “urgency” shouldnot heavily influence the clinician’s decision to proceedto an operation.79,80 All psychological and non-motorfeatures should be stabilized before consideration forsurgery. The evaluating team should be aware that theusual onset of TS occurs before the age of 10 yearsand has an average onset of 5.6 years. Tics typicallyfollow a waxing and waning course, and they peak inseverity in early adolescence. This peak is followed inmost cases by a gradual reduction in tic severity in lateadolescence and early adulthood.6,81 Longitudinalstudies have reported either complete remission oralternatively mild tics in early adulthood for more thantwo thirds of TS patients.5,6 Clinicians selecting DBScandidates would likely benefit from a list of predictivefactors that would facilitate identification of patientswho will remain severely affected into adulthood. Thisinformation is not currently known. Recent researchsuggests that tic severity, premonitory urges, and afamily history of TS may be childhood predictors of aworse health-related quality of life in adulthood.82
Although TS rarely causes severe disability, and gen-erally has a favorable prognosis, in a small subset ofpatients the symptoms cause severe disruption of inter-personal relationships, as well as impairments ofsocial, psychological, and intellectual development. Inextreme cases, TS may even become life threatening(eg, whiplash tics causing vertebral artery dissection83
or myelopathy84). This severe form of the syndrome isassociated with a higher rate of behavioral comorbid-ities (particularly OCD) and is more likely to berefractory to conservative medical management.Although malignant TS may affect only 5.1% of allTS patients, these cases will frequently come to theattention of TS DBS teams.85
The appropriate age to perform TS DBS isunknown and has been widely debated. In 2006, thefirst TSA guidelines7 proposed a minimum age crite-rion of 25 years to ensure that individuals who mightexperience spontaneous tic remission would not beimplanted with a surgical device. Since that time,
compelling arguments have been made for considera-tion of surgical intervention at younger ages in cer-tain cases of severe TS.86,87 The risk–benefit data forTS and for other DBS indications have shown thatthe actual DBS procedure is safe and well tolerated inchildren, particularly as demonstrated in those withdystonia.88 Because of increased evidence of a favor-able risk–benefit ratio for DBS in children with dysto-nia and TS, the age guideline has been adjusted bymost experts to recommend a multidisciplinary evalu-ation and discussion, without setting a firm age limit.Delaying surgery in younger incapacitated TSpatients could potentially result in irreparable harmto social, psychological, and intellectual development,even if the symptoms eventually subside with age.Similarly, in rare cases of “malignant tics” that occurin younger individuals, the tics themselves (eg, whip-lash tics) may carry greater risk for bodily harm,paralysis, or even death.A feature of TS with implications for determining
the efficacy of DBS is its frequent association with dis-abling psychiatric and behavioral comorbidities. Themost common of these are ADHD and OCD. Comor-bidities have a significant negative impact on the qual-ity of life in TS and can be a larger source ofimpairment when compared with motor tics.89,90 Iden-tification of comorbid psychiatric symptoms is criticalfor a DBS workup, because when left untreated, thesesymptoms may be the best predictors of a worse qual-ity of life, with or without DBS therapy.91 Comorbidsymptoms should be adequately treated before sur-gery, and patients should be informed that individualswho are deemed to be good candidates for DBS mayexperience a 30% to 50% or greater improvement inmotor tics. However, based on all available publishedcases, how DBS will impact TS comorbidities remainsunclear. Notably, comorbid OCD, ADHD, and moodissues have improved after DBS in some but not allcases.31,33,36,45,52,54,57,58,63,65,66
Deep brain stimulation should be offered to TSpatients only after evaluation by a multidisciplinary orinterdisciplinary team. This team should includeexperts in TS and associated comorbidities (ie, neurol-ogist, neurosurgeon, psychiatrist, neuropsychologist,DBS programmer [nurse or physician]). Centers per-forming DBS should have a high level of expertisewith DBS therapy, especially given the complexities ofthe TS patient. Potential therapy candidates should beindependently evaluated by each member of the team,and discussion of candidacy, risks, benefits, operativeapproach, and postoperative care should be pursuedbefore a decision on candidacy is reached.The ideal DBS candidate will have a DSM V diagno-
sis of TS and severe motor and vocal tics, whichdespite exhaustive medical and behavioral treatmenttrials result in significant impairment of self-esteem,
S C H R O C K E T A L
18 Movement Disorders, Vol. 00, No. 00, 2014
social acceptance, family life, school or job functioning,or physical well-being. Psychosocial, medical, neurolog-ical, or psychiatric conditions that increase the risk ofthe procedure, preclude full participation in the opera-tion or post-DBS care, or that will potentially compro-mise the accurate assessment of outcomes should all beaddressed by the DBS multidisciplinary team beforesurgery. Tics and comorbid conditions should be opti-mally treated medically and behaviorally per currentexpert standards.3,9 Deep brain stimulation should notbe performed during periods of severe psychosocialinstability, which is likely to interfere with the closemonitoring and follow-up required. Psychosocial stressalso may increase the risk of suicide after surgery.92,93
In general, DBS surgery should be avoided if a patientis judged to be at imminent risk of suicide.80
Inclusion and Exclusion Criteria
A DSM V diagnosis of TS should be made by anexpert clinician who has experience in the evaluationand management of tic disorders (updated from DSMIV). Age should no longer be a strict criterion. Deepbrain stimulation should be considered only when allstandard medical and behavioral therapies have failedregardless of the patient’s age. Tourette syndromeDBS should rarely be an urgent indication, with thepossible exception of impending paralysis from head-snapping tics or profound SIB. A local ethics commit-tee or institutional review board should be consultedfor consideration of cases involving persons youngerthan 18 years of age, as well as in cases with urgentindications, particularly those with lower YGTSSscores or with shorter durations of symptoms.
TABLE 3. Pre- and post-operative outcome measures rec-ommended by the TSA*
Preoperative Information: Patient Assessment and SelectionAge, sex, ethnicityAge of TS onsetAge at diagnosis of TSAge at time of surgeryPsychiatric comorbidities (OCB, ADHD, depression, anxiety, SIB, other)TS medications tried and stopped bfore DBS (medication name, dose,and duration of trial)TS medications at the time of DBS (including dose)Documentation of CBIT being offered or of the trial and outcomeStandardized evaluation of tic type and severity (pre- and post-operatively)
Yale Global Tic Severity Score (YGTSS)Blinded video-based rating (e.g., Rush video scale rating of body
regions involved, tic severity and frequency)Premonitory Urge for Tics Scale 132
Clinical Global Impression (CGI for TS)Standardized evaluation of comorbid symptoms with valid and reliableinstruments when available (pre- and post-operatively)
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)Conners’ Adult ADHD Rating Scale (CAARS)Depression: Beck Depression Inventory, 2nd Ed. (BDI-2), Hamilton
Depression Rating Scale (HDRS), Montgomery-Asberg Depression RatingScale (MADRS)
Anxiety: Hamilton Anxiety Rating Scale (HARS), State-Trait AnxietyInventory (STAI)
Mania: Young Mania Rating Scale (YMRS), K-SADS Mania RatingScale (MRS)
CGI (for ADHD and OCD)Suicide Assessment Scale (e.g., Columbia Suicide Severity Rating
Scale)Quality of Life Measurement (eg, Gilles-de-la-Tourette-Syndrome Qual-ity-of-Life scale [GTS-QOL], Global Assessment of Functioning scale[GAF], SF-36)
Surgical information: targeting and lead locationBrain target (eg, CM-Pfc-Voa thalamus, Gpi, ALIC/NA, other)Procedure (unilateral, bilateral, simultaneous, staged)Lead models and IPG models used (eg, Medtronic 3387/3389, ANS,Neuropace, primary cell, rechargeable, other)Lead location verification with postoperative MRI or CT (x-y-z coordi-nates of each contact in relation to the midcommissural point)
Postoperative information: programming, outcome data and adverse eventsStimulation parameters (active contacts, amplitude or current, fre-quency, pulse width, 6 impedence) at each follow-up visit and timeduration at that settingFrequency of programming adjustments (# to optimization, # per year)Stimulation-induced and general adverse effects
Psychiatric/cognitive (exacerbation of tics, mania, hypomania, cogni-tive decline, anxiety, OCB, depression, smile or laughter induction,impulsivity, psychosis, suicidal ideation/attempt, completed suicide,other)
General (paresthesias, muscle contractions, dyskinesias, bradykinesia,dystonia, dysarthria, stuttering, nausea or vertigo, lethargy, gait disorder,sexual side effects, weight loss/gain >10 pounds, death, other)Intraoperative or early surgical (1st post-op week) adverse events(symptomatic/asymptomatic hemorrhage, ischemic stroke, seizure, post-op confusion, infection, air embolism, DVT, death, other)Delayed surgical adverse events (infection of intracranial lead, extracra-nial lead/lead extender infection, infection of IPG, lead dislodgment, leadfracture, lead revision, suboptimally positioned lead, lead removal, IPGremoval, other)Timing of IPG replacement or need for recharging
(Continued)
Regular postoperative evaluations to include standardized rating scalesof TS and co-morbidities
YGTSSBlinded video-based ratingY-BOCSPremonitory Urge for Tics Scale (PUTS) 132
Conner’s ADHD ScaleDepression: BDI-2, HDRS or MADRSAnxiety: HARS, STAIMania: YMRS, K-SADS, MRSCGISuicide Assessment Scale (eg, Columbia Suicide Severity Rating
Scale)
a The exact measures are less important than the adherence to measure-ment of pre/post outcomes in each of the major domains (motor, non-motor, mood, quality of life).TSA, Tourette Syndrome Association; TS, Tourette syndrome; OCB, obses-sive compulsive behaviors; ADHD, attention deficit hyperactivity disorder;SIB, self-injurious behavior; DBS, deep brain stimulation; CBIT, cognitivebehavioral intervention therapy; K-SADS, kiddie schedule for affective dis-orders and schizophrenia; OCD, obsessive-compulsive disorder; SF-36,short form health surgery 36; CM-Pfc-Voa, centromedian nucleus-parafas-cicular complex; Gpi, globus pallipus internus; ALIC/NA, anterior limb ofthe internal capsule/nucleus accumbens; IPG, implantable—pulse genera-tor; MRI, magnetic resonance imaging; CT, computed tomography; DVT,deep venus thrombosis.
T O U R E T T E S Y N D R O M E D B S G U I D E L I N E S
Movement Disorders, Vol. 00, No. 00, 2014 19
The candidate should have a chronic and severe ticdisorder with severe functional impairment. A standar-dized videotape assessment (eg, Rush Video-Based TicRating Scale94) and a validated rating scale (eg, YaleGlobal Tic Severity Scale [YGTSS]95) should be usedto document tic severity. In most cases the TS patientshould have a total YGTSS score greater than 35/50documented over the course of a year.Motor or vocal tics should be the primary symp-
tom causing disability for a patient. Although mostcandidates are likely to have comorbid ADHD,OCD, depression, anxiety, or other non-motor symp-toms, these symptoms should be adequately treatedand stable for a minimum of 6 months and shouldnot be the major source of functional impairment. Insome patients, the commonly noted comorbidity ofSIB, particularly severe SIB,96 may be inextricablyintertwined with tics, and thus may be a primarycontributor to disability. Patients with SIB or pickingbehavior should be warned preoperatively of anincreased risk of infection or hardware-relatedcomplications.64
At a minimum, documentation of unsuccessful treat-ment trials is needed from three pharmacologicalclasses: (1) an alpha-adrenergic agonist, (2) two dopa-mine antagonists (including one typical and one atypi-cal), and (3) a drug from at least one additional class(e.g., clonazepam, topiramate, or tetrabenazine). Tet-
rabenazine should be tried if accessible.97,98 In addi-tion, CBIT delivered by a trained CBIT therapistshould be offered,2,4 and the patient must have dem-onstrated his or her ability to adhere to recommendedtreatment plans before serious surgical consideration.Unfortunately, in many locations, including some cen-ters experienced with TS, substantial issues of access,wait times, and lack of insurance reimbursement maketherapies such as CBIT not always feasible, particu-larly in cases of malignant TS.The neuropsychological profile must indicate that the
candidate will be well suited to tolerate the surgical proce-dure, rigorous postoperative follow-up, and the possibilityof both a negative or positive outcome.87 The potential forprogressive cognitive impairment should be absent on thisprofile, or a follow-up profile should be performed to con-firm findings and to also track progression.Because of the substantial time commitment
required for optimization of DBS therapy, as well asthe significant impact that psychosocial factors canhave on the disorder, any candidate for TS DBS musthave adequate social support, and there should not beacute or subacute psychosocial stressors. A caregivermust be available to accompany the patient for visitsand for frequent programming.Similar to that proposed in the previous guidelines,
there should be documentation of no suicidal idea-tion and no psychiatric hospitalization for 6 monthsbefore surgery. Depression and mood disorders mustbe stable and treated. Preferably suicidal tendencyshould be monitored preoperatively and postopera-tively with a scale such as the Columbia SuicideScale99 or another similar measure. Active or recentdependence on drugs or alcohol are contraindicationsfor surgery. No structural lesions should be seen onmagnetic resonance imaging that are deemed to pres-ent a significant risk by the neurosurgeon, nor medi-cal, neurological, or cognitive disorders that wouldsignificantly increase the risk of a failed procedure,surgical complications, or interfere with postopera-tive management. A new criterion employed by mostcenters involved with TS DBS since 2006 is that anexpert clinician should feel comfortable that malin-gering, factitious disorder, or psychogenic tics are notpresent.Teams implanting TS patients should record preop-
erative and postoperative outcome measures, includingage, disease duration, tic subtypes, motor, mood,behavior, quality of life, medications, postoperativelead locations, stimulation settings, and suicidal ten-dencies. Validated clinical rating scales of tics and TScomorbidities are critical. A full list of the measuresrecommended by the TSA and employed in in theInternational TSA DBS Database/Registry is providedin Table 3. The exact measures are less importantthan the adherence to measurement of preoperative
TABLE 4. TS DBS Inclusion and Exclusion Criteria
Inclusion Criteria Exclusion Criteria
1. DSM-V Diagnosis of TS by expertclinician2. Age is not a strict criterion. Localethics committee involvement forcases involving persons < 18 years,and for cases considered “urgent”(eg, impending paralysis from head-snapping tics)3. Tic Severity: YGTSS >35/504. Tics are primary cause ofdisability5. Tics are refractory to conservativetherapy (failed trials of medicationsfrom 3 classes, CBIT offered)6. Co-morbid medical, neurological,
and psychiatric disorders are treatedand stable 3 6 months7. Psychosocial environment is stable8. Demonstrated ability to adhere torecommended treatments9. Neuropsychological profile indi-cates candidate can toleratedemands of surgery, postoperativefollow-up, and possibility of pooroutcome
1. Active suicidal or homicidalideation within 6 months2. Active or recent substanceabuse3. Structural lesions on brainMRI4. Medical, neurological, orpsychiatric disorders thatincrease the risk of a failedprocedure or interferencewith postoperativemanagement5. Malingering, factitious dis-order, or psychogenic tics
TS, Tourette syndrome; DBS, deep brain stimulation; DSM-V, Diagnosticand Statistical Manual of Mental Disorders; YGTSS, Yale Global Tic Sever-ity Scale; CBIT, cognitive behavioral intervention therapy.
S C H R O C K E T A L
20 Movement Disorders, Vol. 00, No. 00, 2014
and postoperative outcomes in each of the majordomains (motor, non-motor, mood, quality of life).
Discussion
The centers participating in the TSA InternationalDatabase/Registry have employed several importantpractice pattern changes to the selection and assess-ment recommendations for the use of TS DBS. These
changes were based on the expanded experience in thefield since the 2006 guidelines. The changes and partic-ularly the inclusion criteria (Table 4) reflect the grow-ing experience with more than 120 cases reportedworldwide. In particular, the relative safety of the pro-cedure has been better established. Additionally, someTS cases may be appropriate for DBS before the previ-ously recommended age of 25 years. Most centers nowemploy a multidisciplinary team approach for screeningrather than an age limit. For patients younger than age
FIG. 1. Flow diagram of recommended DBS evaluation process for TS.
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18, one should have additional institutional approval.Centers performing TS DBS should use preoperativeand postoperative outcome measures, regardless ofwhether they adopt the TS DBS Database/Registryguidelines. All patients undergoing TS DBS should beaware that there is a reasonable chance for motor andvocal tic improvement, but that other co-morbidities ingeneral respond less consistently to therapy. Cliniciansshould educate patients and families on the increasedinfection rate, and the potential for increasedhardware-related issues. Figure 1 provides a diagram ofthe recommended evaluation before TS DBS.The most appropriate brain target for an individual
symptom profile remains unknown. The consensus ofthe centers implanting TS DBS includes the following:(1) all adverse events, whether major or minor, surgi-cal or nonsurgical, related or unrelated to the therapy,should be recorded and reported; (2) detailed descrip-tions of all surgical and programming proceduresshould be recorded; and (3) preoperative and postop-erative targeting should be reported, because wherethe optimal target regions are located, even within tar-gets, remains unclear. Psychological issues should bescreened preoperatively and monitored postopera-tively. Finally, rigorous reporting of DBS failures andadverse events is needed.100 Databases and registriesmay be our best hope of advancing the field quickly,because most expert centers will do less than a hand-ful of TS surgeries.After an extensive review of the literature and con-
sensus among implanters of DBS, we conclude that TSDBS, though still evolving, is a promising approachfor a subset of medication-refractory and severelyaffected patients.
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