ios press selection of patients with tourette syndrome for...

Behavioural Neurology 27 (2013) 125–131 125DOI 10.3233/BEN-120288IOS Press

Selection of patients with Tourette syndromefor deep brain stimulation surgery

Mauro Portaa,∗, Andrea E. Cavannab,c, Edvin Zekajd, Francesca D’Addaa and Domenico Servellod

aTourette Centre, IRCCS Galeazzi Hospital, Milan, ItalybThe Michael Trimble Neuropsychiatry Research Group, Department of Neuropsychiatry, BSMHFT and Universityof Birmingham, Birmingham, UKcSobell Department of Motor Neuroscience and Movement Disorders, UCL and Institute of Neurology, London, UKdFunctional Neurosurgery Unit, IRCCS Galeazzi Hospital, Milan, Italy

Abstract. Deep brain stimulation (DBS) is an emerging therapeutic option for severe resistant Tourette syndrome (TS). To date,about 100 cases have been reported in the scientific literature. Different clinical guidelines have been proposed for this procedurefrom both USA and European centres. A number of issues remain unresolved, mainly in relation to eligibility criteria of patientswith TS. We highlight the need for a comprehensive assessment of associated co-morbidities, which are not considered integralpart of the syndrome and are not sufficiently evaluated in relation to DBS. The concept of refractoriness, the minimum age ofcandidates, and the optimal targets for DBS are also controversial.

Keywords: Deep brain stimulation, Tourette syndrome, tics, co-morbidities, selection criteria

1. Introduction

Tourette syndrome (TS) is a chronic neurodevelop-mental disorder defined by the presence of multiplemotor tics and at least one phonic tic [1]. It is estimatedthat about 90% of patients have at least one co-morbidbehavioural symptom, such as attention deficit hyper-activity disorder (ADHD), obsessive-compulsive dis-order (OCD), self-injurious behaviour (SIB), impulsedyscontrol and affective dysregulation [2]. Overall, thecourse of tic symptoms is relatively favourable overtime: up to 50% of patients with onset of tic disorderbefore age 10 experience a significant decrease in ticseverity during adolescence [3]. However, severe TScan have devastating effects on perceived well beingand relationships. Behavioural strategies, in additionto both standard and innovative pharmacological ther-apies, are the main treatment interventions for patients

∗Corresponding author: Mauro Porta, Tourette Centre, IRCCSGaleazzi Hospital, Via R. Galeazzi 4, 20161 Milan, Italy. Tel.:+39 02/66214933; Fax: +39 02/66214916; E-mail: [email protected].

who continue to experience severe symptoms with sig-nificant social impairment.

When patients are refractory to conservative treat-ments, deep brain stimulation (DBS) could be consid-ered as an emerging therapeutic option. Over the lastfew decades, DBS has been demonstrated to be a safeand efficacious procedure in different movement disor-ders, including Parkinson disease, essential tremor anddystonia [4]. More recently, DBS has also been usedto treat patients with severe and refractory psychiatricdisorders, such as OCD and depression [5].

The rationale for choosing specific targets for DBSto treat patients with severe and refractory TS was ini-tially based on the effects of historical procedures ofablative surgery, which are no longer ethically accept-able [6]. The results of preliminary reports on DBS inTS are encouraging, even though many aspects haveyet to be better clarified, in primis the issue of patientselection [7].

2. Assessment

Candidates to DBS in TS should undergo a compre-hensive neurological, neuropsychiatric and neuropsy-

ISSN 0953-4180/13/$27.50 2013 – IOS Press and the authors. All rights reserved

126 M. Porta et al. / Selection of patients with Tourette syndrome for deep brain stimulation surgery

chological pre-surgical assessment, to be carried outby a multidisciplinary team with clinical experience inTS and in collaboration with functional neurosurgeons.Detailed clinical assessment guidelines of tic disordersand common co-morbidities are discussed in the recent-ly published guidelines from the European Society forthe Study of Tourette Syndrome (ESSTS) [8]. Patientsshould be diagnosed according to DSM IV-TR criteriaand the diagnosis should be validated by instrumentssuch as the TS Diagnostic Confidence Index. With re-gards to the clinical picture, the tic symptoms shouldrepresent the primary problem significantly affectingQuality of Life (QoL).

Tic severity should be evaluated by means of directobservation (e.g. videorecording) and clinical scales,such as the Yale Global Tic Severity Scale (YGTSS).A YGTSS total tic severity score above 35/50 duringrepeated assessments for at least six months is a re-liable indicator of a degree of tic severity promptingconsideration of DBS.

The large majority of patients with TS have co-morbid psychopathology, including attention-deficitand hyperactivity disorder (ADHD), obsessive-compulsive disorders (OCD), anger control problems,mood disorders, conduct and oppositional defiant disor-ders. Co-morbidities have to be evaluated using specificscales: for example, the Yale-Brown Obsessive Com-pulsive Scale (YBOCS) has often been used for eval-uation of obsessive compulsive behaviours; the State-Trait Anxiety Inventory (STAI) assesses patients’ stateand trait anxiety, and the Beck Depression Invento-ry (BDI) reliably measures depression. It should al-ways be considered that co-morbidity can representthe main reason to seek help in patients with TS. Thedisease-specific health-related quality of life scale forTS (GTS-QOL) developed by Cavanna et al. [9] high-lights the relevance of the patient’s subjective point ofview. This scale comprises 27 items which examinefour components of quality of life: the psychologicaldomain, the physical/activities of daily living (ADL)domain, the obsessive-compulsive domain and the cog-nitive domain. Importantly, this scale can adequatelyand specifically evaluate aspects of social impairmentwhich often motivate DBS in refractory patients. TheGTS-QOL also captures other aspects of the TS-relatedimpact on life. Self injurious behaviour (SIB) is fre-quently present in the context of TS. For example, SIBof different severity was reported in 46.1% of patientsfrom a clinical sample of 639 subjects [10]. Patientswith life-threatening tics are classified as having “ma-lignant TS”. Jankovic et al. [11] in their experience

reported that 5% of patients with TS can present ma-lignant TS, often in association with severe obsessive-compulsive symptomatology. Finally, the GTS-QOLcan prove useful both as baseline and outcomemeasure,also in the longer term. For instance, a recent studyshowed that young patients with severe tics associat-ed with characteristic premonitory urges and a familyhistory of tics disorders appear to be at higher risk forpoorer quality of life as adults [12].

Both environmental and psychosocial stressors haveto be evaluated as factors aggravating clinical symp-toms. Surgical candidates should experience tics asso-ciated with a significant functional impairment.

“TS by history” has to be carefully evaluated by ask-ing patients, parents and caregivers. These data can behighly informative, although the value of these parame-ters is not yet formally validated. At least familiar, envi-ronmental and economic issues have to be carefully ex-amined as they are important factors that may influencepatient compliance. Analysis of the phenomenologicalaspects of TS according to Jankovic [13] seems essen-tial to choose targets for DBS; videotaping according toKompoliti and Goetz [14] and accelerometry [15] canbe used to objectively evaluate tic symptoms. The pa-tient or his/her legal representative must given writteninformed consent before the DBS procedure. If DBSis performed in the context of a trial, the study designhas to be approved by the local ethics committee [16].

3. Treatment refractoriness

The exact definition of treatment refractoriness in TShas been debated [17]. A significant percentage of pa-tients with TS show spontaneous improvement up to acomplete disappearance of most if not all the symptomsduring adulthood: DBS is of course indicated for thosepatients failing to show such improvement of symp-toms and related social impairment [18]. The therapeu-tic strategies used to treat tics and co-morbidities arefar from being standardized; although there are manyopen studies on pharmacotherapy, only a limited num-ber of studies meets rigorous criteria for therapeutic tri-als. Cochrane reviews and expert views on the pharma-cological treatment of TS have recently been published(Fig. 1) [19,20].

Drug therapy often involves the use of antipsychoticagents, which can be associated with a higher risk ofadverse effects compared to other drugs. Side effectsmay persist during adulthood: this fact by itself rep-resent an important element in evaluating refractori-

M. Porta et al. / Selection of patients with Tourette syndrome for deep brain stimulation surgery 127

Fig. 1. Proposed algorithm for the treatment of Tourette syndrome, based on the authors’ interpretation of evidence-based literature and theirown experience (cfr. [20]).

ness. In the scientific literature, drug protocols usedbefore DBS in patients with TS are rarely reportedin details [21,22]. Some authors described the use of“maximum dose of established treatments” [23], or “aninadequate response to at least two dopamine blockersor catecholamine depletors” [24], or “failure of besttreatment by medication (antipsychotics), or intoler-ance after a minimumof 6 months of treatment”, beforeDBS [25]. In our department (IRCCS Galeazzi, Mi-lan, Italy), patients with TS are considered treatment-refractory when they failed to respond to a behaviouralintervention, such as habit reversal training, and ther-apeutic doses of at least three medications of provenefficacy for tics, including antidopaminergic drugs (i.e.haloperidol, pimozide, risperidone, tiapride, sulpiride,aripiprazole), α-2 adrenergic agonists (i.e. clonidineand guanfacine), and SSRIs (selective serotonin reup-take inhibitors). Refractoriness is also established bylack of response to innovative drugs, which are oftenprescribed off label.

4. Patient age

Age is an issue of particular relevance for the se-lection of surgical candidates in TS, since spontaneous

remission by the age of 18 has been shown to occur innearly half of the patients [3]. Performing DBS surgerytoo early in a patient who can undergo spontaneous im-provementmeans to expose him/her to unnecessary sur-gical risks, despite the fact that DBS is a mini-invasive,reversible, adjustable procedure. On the other hand,delaying the intervention in patients with severe TSsymptoms can expose them to a considerable disadvan-tage, in terms of quality of life, education, and socialinclusion. It is well known that the age from 18 to25 years is a crucial phase for schooling and vocationalqualification, thus the presence of severe tics and co-morbidities can lead to far-reaching consequences, in-cluding permanent social impairment [26,27]. In fact,it is during developmental age that clinical stigmata ofthe disorder cause the most significant damage, severe-ly and permanently altering the social functioning ofthe patient, in some cases to such an extent that evenafter regression of symptoms return to normal sociallife is almost impossible.

5. Target choice

At least eight targets for DBS in patients with TShave been reported. Most studies report experience


with small case series (less than five). Overall, in thisdecade DBS for TS has brought more questions thananswers. In our department, fifty patients with TS havebeen treated with DBS. The most targeted area wasthe ventro-oralis-centromedian-parafascicular nucleusof the thalamus Vo-Cm-Pf (Lat: 5 mm, AP: −2 mm,Z: 0 mm), with optimal results concerning tics and im-provement in OCD and anxiety [28,29]. Stimulationof the nucleus accumbens-anterior limb of the internalcapsule (NA-ALIC) was used as first line procedureor as rescue procedure for patients with relevant OCDwho failed to respond to Vo-Cm-Pf stimulation. In se-lected patients with prevalence of dystonic tics, signif-icant reduction of tic severity was obtained targetingthe posterior portion of the globus pallidus-pars interna(Gpi). In patients with a clinical picture characterisedby significant co-morbidities, we targeted the anteriorportion of the GPi [30]. In our opinion, targets shouldbe selected case by case on the basis of the most rele-vant symptoms (tailoring approach), as different targetsseem to have different clinical effects.

6. Compliance

Poor patient and caregivers compliance should beconsidered as a major exclusion criterion. Patient withhistory of drug addiction have to be carefully evaluat-ed. The role of caregivers in determining outcome ofDBS is poorly elucidated. Frequently caregivers maynot appreciate amelioration of symptomatology afterDBS. The risk is to produce frustration on the patientsand decrease the compliance. In most cases physiciansfocus on patient compliance, while caregiver’s com-pliance is frequently underestimated. From our experi-ence we have learnt that caregiver compliance can beas important as patient compliance. We have had twodisposal removals due to caregiver’s poor compliancewhich prevailed over patient will, convincing them ofthe failure of the surgical procedure. In order to be eli-gible for DBS, patients should demonstrate compliancewith previous treatments [31]. Compliance should beassessed in terms of adherence to pharmacological pro-tocols and psychobehavioural training programs, andattendance to follow-up visits.

7. Other exclusion criteria

A controversial issue within exclusion criteria is thefinding of brain abnormalities on pre-operative MRI

scans. In clinical series of dystonic patients, focal sig-nal abnormalities in the basal ganglia do not contraindi-cate DBS [32]. On the other hand, in Parkinson dis-ease the presence of chronic ischemic disease or dif-fuse cerebral atrophy compatible with atypical Parkin-sonism represent exclusion criteria for DBS. In our TSseries, the presence of vascular abnormalities affectedthe positioning of the stimulating electrode near thetarget [33]. There are uncertainties also with regardsto general medical conditions representing contraindi-cation to DSB. In various reports, cardiovascular, pul-monary or hematological disorders are considered acontraindication for surgery. In our opinion, patientsshould be excluded from surgery if they have an Amer-ican Society of Anesthesiologists (ASA)score of 3 orabove which represent an increased risk for generalanaesthesia.

Another important aspect related to exclusion crite-ria is the presence of severe psychiatric co-morbidity.With regards to this, it has to be considered that about90% of patients with TS have at least one co-morbidbehavioural symptom, such as ADHD, OCD, SIB, im-pulse dyscontrol and affective dysregulation [2]. Thescientific literature is controversial about psychiatricdisorders representing exclusion criteria for DBS. Forinstance, Mink et al. [16] recommend that candidatesto DBS must not have co-morbid psychiatric disorders,while Shahed et al. [30] proposed that psychiatric co-morbidities in TS should not necessarily represent anexclusion criterion, because it is possible that these be-havioural problems will also improve with DBS. It ismandatory to evaluate psychiatric disorder case by case,while previous suicidal attempts should be considereda contraindication.

8. Conclusion

Different guidelines on the selection of candidatesfor DBS in TS have been published to date (Table 1).

From the critical evaluation of these guidelinesemerges a substantial difference regarding the mini-mum age at which DBS might be considered. As statedabove, we believe that surgical procedure have to beproposed to younger patients, starting from the age of18 years. It should also be highlighted that exceptionsin terms of younger patients may be considered forDBS when needed, as in the case of the 16-year-old pa-tient reported by Shahed et al. [30]. The second prob-lem concerns the behavioural spectrum of TS, whichis referred to as co-morbidity. The phenotype of TS


Tabl

e1

Publ

ishe

dgu

idel

ines

forth

ese

lect

ion

ofca

ndid

ates

forde

epbr

ain

stim

ulat

ion

inTo

uret

tesy

ndro

me

TSA

-Am

eric

anG

uide

lines

[18]

Dut

ch-F

lem

ish

Gui

delin

es[3

4]Ital

ian

Gui

delin

es[3

5]Eur

opea

nG

uide

lines

[16]

UK

pers

pect

ive

[36]

Yea

rof

publ

icat

ion

2006

2006

2009

2011

2011

Patie

nt’s

age

25+

rare

exce

ptio

ns25

+18

+ra

reex

cept

ions

18+

20+

Dia

gnos

isN

ose

vere

adul

tca

ses

that

wer

em

ild-m

oder

ate

inch

ildho

odTw

oin

depe

nden

tra

ters

usin

gD

SM-I

Van

dD

iagn

ostic

Con

-fid

ence

Inde

x

Tra

ined

rate

rus

ing

DSM

-IV-

TR

TS

orch

roni

ctic

diso

rder

diag

nose

dby

anex

perien

ced

clin

icia

nM

ultid

isci

plin

ary

team

–D

SM-

IV-T

RD

iagn

ostic

Con

fiden

ceIn

dex

Sym

ptom

sse

verity

YG

TSS

>35

/50

for

12m

onth

s,vi

deot

apin

gan

dfa

mily

inte

rvie

wY

GTSS

>20

/50

and

Soci

alIm

pairm

ent>

5/50

,vid

eota

ping

YG

TSS

�35

/50

Mot

ortic

subs

core�

15,t

ics

caus

ing

dist

ress

,SIB

YG

TSS

�35

/50,

tics

shou

ldbe

se-

vere

fora

tlea

st1

year

and

last

ing

atm

inim

um5

year

sbe

fore

DB

S

YG

TSS

�35

/50,

atle

ast12

mon

ths

for

surg

ery.

Litt

leho

pefo

rsp

onta

-ne

ous

impr

ovem

ent.

Rep

eate

dev

alua

tions

ofQ

oL

Co-

mor

bidi

ties

Bas

elin

eas

sess

men

tofco

-m

orbi

ditie

san

dst

able

trea

tmen

tfo

r6

mon

ths

Tic

sar

epr

imar

ypr

oble

m(e

.g.

not

OC

Dor

SIB

aspr

imar

ypr

oble

m)

Ext

ensive

asse

ssm

entt

oid

en-

tify

pote

ntia

lco

mpl

icat

ions

(e.g

.som

atis

atio

n)

Tic

sar

epr

imar

ypr

oble

m,

co-

mor

bidi

ties

(AD

HD

,OC

D,d

epre

s-si

on,a

nxie

ty,S

IB)h

avebe

entrea

ted

acco

rdin

gto

resp

ectiv

egu

idel

ines

Stru

ctur

albr

ain

anom

alie

san

dco

agul

opat

hies

,O

CD

and

AD

-H

Dar

ehi

ghly

prev

alen

tin

TS

Tre

atm

ent

refr

acto

rine

sscr

iteria

Failu

reto

resp

ond

to(o

rse

vere

side

effe

cts

from

):α

-2ad

ren-

ergi

cag

onis

t,ty

pica

lan

dat

yp-

ical

antip

sych

otic

san

dbe

nzod

i-az

epin

es,b

ehav

iour

alth

erap

y

No/

partia

lre

spon

seto

3m

ed-

icat

ions

(for

12w

eeks

):ty

pi-

calan

dat

ypic

alan

tipsy

chot

ics

and

‘exp

erim

enta

l’dr

ug,

12se

ssio

nsof

beha

viou

ral

ther

-ap

y(H

abit

Rev

ersa

lThe

rapy

and

Exp

osur

ean

dR

espo

nse

Prev

entio

n)

Lac

kof

resp

onse

orin

tole

ra-

ble

adve

rse

effe

cts

toty

pica

lan

dat

ypic

alne

urol

eptic

san

din

nova

tive

trea

tmen

ts

Tre

atm

ent

with

3di

ffer

ent

drug

sin

clud

ing

both

typi

cal

and

atyp

i-ca

lneu

role

ptic

sin

adeq

uate

dosa

geov

eran

adeq

uate

period

oftim

edo

esno

tres

ulti

nsi

gnifi

cant

ticre

duct

ion

orle

adsto

unac

cept

able

adve

rse

ef-

fect

s.B

ehav

iour

altrea

tmen

tfo

r12

sess

ions

with

oute

ffec

t

The

rape

utic

dose

sof

atle

ast

3m

edic

atio

nspr

oven

effic

a-ci

ous

for

tics,

incl

udin

gan

ti-do

pam

iner

gic

drug

s(H

alop

eri-

dol,

Pim

ozid

e,R

ispe

rido

nean

dA

ripi

praz

ole)

and

α-2

adre

ner-

gic

agon

ists

(Clo

nidi

ne)

Oth

erpa

tient

spec

ifica

tions

Will

ingn

ess

toen

gage

inon

go-

ing

trea

tmen

t,go

odco

mpl

ianc

e,co

nsid

erps

ycho

soci

aldi

fficu

lties

Abi

lity

tom

akea‘c

ompl

ete

de-

cisi

on’to

partic

ipat

e,em

phas

ison

ethi

csan

drigh

tto

with

draw

Ass

essm

ento

ftrea

tmen

tco

mpl

ianc

e,sy

mpt

omre

late

ddi

fficu

lties

inso

cial

life

Tic

scau

seso

cial

impa

irm

enti

nQ

oL(r

elat

ions

hips

,ho

me

envi

ronm

ent,

scho

ol/w

ork)

.C

ompl

ianc

ean

dst

a-bl

eps

ycho

soci

alen

viro

nmen

t

Patie

nts

shou

ldbe

rece

ivin

gst

able

and

optim

ized

trea

tmen

tfo

rco

-mor

bid

cond

ition

sfo

r6

mon

thspr

iorto

surg

ery

Patie

ntex

clus

ion

crite

ria

Tic

sat

trib

utab

leto

othe

rdi

sor-

der,

seve

re/c

ontrai

ndic

ated

med

-ic

alor

psyc

hiat

ric

cond

ition

s

Tic

sat

trib

utab

leto

othe

rdi

s-or

ders

,se

vere

/con

trai

ndic

ated

med

ical

orps

ychi

atric

cond

i-tio

nsor

men

tald

efici

ency

Cog

nitiv

edy

sfun

ctio

n,su

b-st

ance

abus

e,tic

sdu

eto

med

-ic

atio

nor

othe

rtic

diso

rder

,pr

evio

usbr

ain

surg

ery

orab

-no

rmal

imag

ing

findi

ngs

No

tics,

OC

Dsy

mpt

omsor

SIB

that

coul

dca

use

elec

trod

eor

stim

ula-

torda

mag

ing.

No

maj

orde

pres

sion

and/

orsu

icid

alth

ough

tsat

time

ofop

erat

ion.

No

othe

rco

nditi

ons

in-

crea

sing

risk

sin

anae

sthe

sia

orop

-er

ativ

epr

oced

ures

Preg

nanc

yan

dth

epr

esen

ceof

med

ical

orps

ychi

atric

cond

ition

s

Abb

revi

atio

ns:

YG

TSS

,Yal

eG

loba

lTic

Seve

rity

Scal

e;Q

oL,Q

ualit

yof

Life;

AD

HD

,at

tent

ion-

defic

ithy

pera

ctiv

itydi

sord

er;

OC

D,ob

sess

ive-

com

puls

ive

diso

rder

;SI

B,se

lf-inj

urio

usbe

havi

our.


Table 2Proposed inclusion criteria for deep brain stimulation in Tourette syndrome

Eligible candidates for deep brain stimulation should:

– Be above 18 years of age (with possible exceptions)– Be carefully and completely assessed– Be diagnosed according to DSM-IV-TR criteria and Diagnostic Confidence Index standards– Be evaluated in terms of preoperative clinical algorithm (1 year before DBS) in repeated sessions– Present tics and coexisting disorders as primary problem– Undergo thorough evaluation of coexisting disorders using appropriate scales– Show a good compliance– Be evaluated also in term of Tourette “by history”– Experience a stable period of severe tics (YGTSS of 35/50 or above) for at least 12 months prior to surgery– Be treatment-refractory– Be treated conservatively for at least 12 months– Not present any other medical contraindications

is multifaceted, with special attention to behaviouralproblems. The issue of whether TS should still beconsidered as a unitary nosological entity representsa procedural priority. Thus the optimal dissection ofTS in each patient is fundamental to understand whichpatients might benefit from DBS.

In conclusion, TS can no longer be considered a mo-tor disorder and, most importantly, a unitary conditionas previously thought. In consideration of this and thedata discussed above, we propose the inclusion crite-ria for DBS used in our department (Table 2), whichcan be considered a possible platform to establish largemulticenter trials to build evidence for DBS protocolsand targets in TS.

References

[1] American Psychiatric Association. Diagnostic and StatisticalManual of Mental Disorders. Fourth Edition, Text Revision(DSM-IV-TR). Washington, DC:APA; 2000.

[2] Cavanna AE, Servo S, Monaco F, Robertson MM. The be-havioural spectrum of Gilles de la Tourette syndrome. J Neu-ropsychiatry Clin Neurosci 2009; 21: 13-23.

[3] Leckman JF, Zhang H, Vitale A, Lahnin F, Lynch K, BondiC, et al. Course of tic severity in Tourette syndrome: the firstdecades. Pediatrics 1998; 120: 14-19.

[4] Gross RE, Lozano AM. Advances in neurostimulation formovement disorders. Neurol Res 2000; 22: 247-258.

[5] Lujan JL, Chaturved A, McIntyre CC. Tracking the mecha-nisms of deep brain stimulation for neuropsychiatric disorders.Front Biosci 2008; 13: 5892-5904.

[6] Hassler R, Dieckmann G. Relief of obsessive-compulsive dis-orders, phobias and tics by stereotactic coagulations of therostral intralaminar and medial-thalamic nuclei. In: Laiti-nen LV, Livingston K, (eds), Surgical approaches in psychia-try. Proceedings of the Third International Congress of Psy-chosurgery. Cambridge, UK: Garden City Press; 1973; p. 206-212.

[7] Porta M, Sassi M, Servello D. Surgical treatment of Tourette.Oxford University Press 2012; in press.

[8] Cheung MY, Shahed J, Jankovic J. Malignant Tourette syn-drome. Mov Disord 2007; 22(12): 1743-1750.

[9] Cavanna AE, Schrag A Morley D, Orth M, Robertson MM,Joyce E, Critchley HD, Selai C. The Gilles de la Tourettesyndrome-quality of life scale (GTS-QOL): development andvalidation. Neurology 2008; 71(18): 1410-1416.

[10] Cavanna AE, Critchley HD, Orth M, Stern JS, Young MB,Robertson MM. Dissecting the Gilles de la Tourette spectrum:a factor analytic study on 639 patients. J Neurol NeurosurgPsychiatry 2011; 82(12): 1320-1323.

[11] Cheung MY, Shahed J, Jankovic J. Malignant Tourette syn-drome. Mov Disord 2007; 22(12): 1743-1750.

[12] Cavanna AE, David K, Orth M, Robertson MM. Predictorsduring childhood of future health-related quality of life inadults with Giles de la Tourette syndrome. Eur J PaediatrNeurol 2012; in press.

[13] Jankovic J. Phenomenology and classification of tics. In:Jankovic J (Ed). Tourette syndrome. Neurol Cl N Am, Vol. 15,Philadelphia: WB Saunders, 1997: 267-275.

[14] Kompoliti K, Goetz CG. Clinical rating and quantitative as-sessment of tics. In: Neurologic Clinics. Jankovic J, (ed.),Tourette syndrome. Philadelphia: WB Saunders, 1997; 15:239-254.

[15] Bernabei M, Preatoni E, Mendez M, Piccini L, Porta M, An-dreoni G. A novel automatic method for monitoring Tourettemotor tics through a wearable device. Mov Disord 2010;25(12): 1967-1972.

[16] Muller-Vahl KR, Cath DC, Cavanna AE, Dehning S, PortaM, Robertson MM, Visser-Vandewalle V, ESSTS GuidelinesGroup. European clinical guidelines for Tourette syndromeand other tic disorders. Part IV: deep brain stimulation. EurChild Adolesc Psychiatry 2011; 20(4): 209-217.

[17] Porta M, Sassi M, Menghetti C, Servello D. The need for aproper definition of a “treatment refractoriness” in Tourettesyndrome. Front Integr Neurosci 2011; 5: 22.

[18] Mink JW, Walkup J, Frey KA, Como P, Cath D, Delong MR, etal. Patient selection and assessment recommendations for deepbrain stimulation in Tourette syndrome. Mov Disord 2006; 21:1831-1838.

[19] Verdellen C, van de Griendt J, Hartmann A, Murphy T, ESSTSGuidelines Group. European clinical guidelines for Tourettesyndrome and other tic disorders. Part III: behavioural and psy-chosocial interventions. Eur Child Adolesc Psychiatry 2011;20(4): 197-207.

[20] Jankovic J, Kurlan R. Tourette syndrome: Evolving Concepts.Mov Disord 2011; 26(6): 1149-1156.

[21] Panagiotopoulos C, Ronsley R, Elbe D, Davidson J, SmithDH. First do no harm: promoting an evidence-based approach


to atypical antipsychotic use in children and adolescents. JCan Acad Child Adolesc Psychiatry 2010; 19: 124-137.

[22] Pringsheim T, Pearce M. Complications of antipsychotic ther-apy in children with Tourette syndrome. Pediatr Neurol 2010;43(1): 17-20.

[23] Kuhn J, Lenartz D, Mai JK, Huff W, Lee SH, KoulousakisA, Klosterkoetter J, Sturm V. Deep brain stimulation of thenucleus accumbens and the internal capsule in therapeuticallyrefractory Tourette-syndrome. J Neurol 2007; 254(7): 963-965.

[24] Maciunas RJ, Maddux BN, Riley DE, Whitney CM, Schoen-berg MR, Ogrocki PJ, et al. Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adultswith Tourette syndrome. J Neurosurg 2007; 107: 1004-1014.

[25] Welter ML, Mallet L, Houeto JL, Karachi C, Czernecki V,Cornu P, et al. Internal pallidal and thalamic stimulation inpatients with Tourette syndrome. Arch Neurol 2008; 56: 952-957.

[26] Eddy CM, Cavanna AE, Gulisano M, Agodi A, Barchitta M,Calı P, Robertson MM, Rizzo R. Clinical correlates of qualityof life in Tourette syndrome. Mov Disord 2011; 26: 735-738.

[27] Eddy CM, Rizzo R, Gulisano M, Agodi A, Barchitta M, Calı P,Robertson MM, Cavanna AE. Quality of life in young peoplewith Tourette syndrome: A controlled study. J Neurol 2011;258: 291-301.

[28] Servello D, Sassi M, Brambilla A, Porta M, Haq I, FooteKD, Okun MS. De novo and rescue DBS leads for refracto-ry Tourette syndrome patients with severe comorbid OCD: amultiple case report. J Neurol 2009; 256(9): 1533-1539.

[29] Sassi M, Porta M, Servello D. Deep brain stimulation therapy

for treatment-refractory Tourette’s Syndrome: A review. ActaNeurochir (Wien) 2011; 153(3): 639-645.

[30] Shahed J, Poysky J, Kenney C, Simpson R, Jankovic J. GPideep brain stimulation for Tourette syndrome improves ticsand psychiatric comorbidities. Neurology 2007; 68: 159-160.

[31] Eddy CM, Rickards HE, Cavanna AE. The cognitive impactof antiepileptic drugs. Ther Adv Neurol Dis 2011; 4: 380-402.

[32] Gavarini S, Vayssiere N, Delort P, Cif L, Biolsi B, TancuC, Vasques X, Plagnol S, Bonafe A, Coubes P. StereotacticMRI in DYT1 dystonia: Focal signal abnormalities in thebasal ganglia do not contraindicate deep brain stimulation.Stereotact Funct Neurosurg 2008; 86(4): 245-252.

[33] Servello D, Sassi M, Brambilla A, Defendi S, Porta M. Long-Term, Post-Deep Brain Stimulation Management of a Seriesof 36 Patients affected with refractory Gilles de la Tourettesyndrome. Neuromodulation 2010; 13: 187-194.

[34] Ackermans L, Temel Y, Cath D, van der Linden C, BruggemanR, Kleijer M, Nederveen P, Schruers K, Colle H, Tijssen MA,Visser-Vandewalle V, Dutch Flemish Tourette Surgery StudyGroup. Deep brain stimulation in Tourette’s syndrome: Twotargets? Mov Disord 2006; 21(5): 709-713.

[35] Porta M, Servello D, Sassi M, Brambilla A, Defendi S, PrioriA, Robertson M. Issues related to deep brain stimulation fortreatment refractory Tourette syndrome. Eur Neurol 2009; 62:264-273.

[36] Cavanna AE, Eddy CM, Mitchell R, Pall H, Mitchell I, ZrinzoL, et al. An approach to deep brain stimulation for severetreatment-refractory Tourette syndrome: the UK perspective.Br J Neurosurg 2011; 25(1): 38-44.

Submit your manuscripts athttp://www.hindawi.com

Stem CellsInternational

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014

Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinson’s Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

ios press selection of patients with tourette syndrome for...

Documents