Health-related quality of life in Gilles de la Tourette syndrome

12 Pages·2014·1.24 MB·English

BehaviouralNeurology27(2013)83–93 83
DOI10.3233/BEN-120296
IOSPress
Review Article
Health-related quality of life in Gilles de la
Tourette syndrome: A decade of research
a,b,∗ b c c
AndreaEugenioCavanna ,KateDavid ,ValentinaBandera ,CristianoTermine ,
d a,e a
UmbertoBalottin ,AnetteSchrag andCarolineSelai
aSobellDepartmentofMovementDisorders,InstituteofNeurologyandUniversityCollegeLondon,London,UK
bDepartmentofNeuropsychiatry,BSMHFTandUniversityofBirmingham,Birmingham,UK
cChildNeuropsychiatryUnit,DepartmentofExperimentalMedicine,UniversityofInsubria,Varese,Italy
dDepartmentofChildNeurologyandPsychiatry,IRCCS‘C.Mondino’Foundation,UniversityofPavia,Pavia,Italy
eDepartmentofNeurology,RoyalFreeandUniversityCollegeMedicalSchool,London,UK
Abstract.GillesdelaTourettesyndrome(GTS)isaneurodevelopmentalconditioncharacterisedbymultiplemotorandphonic
ticsandassociatedbehaviouralproblems,carryingasignificantburdenonpatients’lives. Althoughthetermhealthrelated-quality
of life (HR-QOL) has only been used in recent years, several studies have long addressed the impact of GTS on physical,
psychological and social aspects of wellbeing of both children and adults with GTS. We set out to answer the question “Is
HR-QOLaffectedbyGTSand,ifso,inwhatdomains?” byconductingasystematicliteraturereviewofpublishedoriginalstudies
addressingHR-QOLinbothchildrenandadultpatientswithGTS.Thisreviewfocusesonthecurrentevidenceontheimpactof
GTSonpatients’lives,mainlyinformedbystudiesusinggenericfunctional impairmentandHR-QOLmeasuresfromthelast
decade,andexpandsonthenewopportunitiesintroducedbytherecentlydevelopedGTS-specificHR-QOLscales(GTS-QOL
andGTS-QOL-C&A).AnalysisofthefirstdecadeofstudiesspecificallyaddressingHR-QOLinGTSsuggeststhatco-morbid
conditionsarekeyfactorsindeterminingHR-QOLinyoungpatients, whilstthepictureismorecomplexinadultswithGTS.
Thesefindingsoffersomegeneraldirectionsforbothcurrentclinicalpracticeandfutureresearch.
Keywords:GillesdelaTourettesyndrome,health-relatedqualityoflife,functionalimpairment,tics,behaviouralproblems
1. ThefunctionalimpactofGillesdelaTourette gard to their location, frequency and severity over
syndromeacrossthelifespan time[2]. GTSaffectsapproximately1%ofschool-age
youngsters and is three to four times more common
inmalesthanfemales[3]. GTSisincreasinglyrecog-
Gillesdela Tourettesyndrome(GTS)isalife-long
nised asa complexdisorder, with a wide spectrum of
neurodevelopmentaldisorder defined by the presence
associated behavioural problems that can accompany
of multiplemotorandphonictics [1]. Ticsare repet-
themotorandphonictics. Theseproblemsincludetic-
itive, uncontrollable movements or vocalizations that
related symptoms (ranging from socially inappropri-
usually presentin childhoodbut may changewith re-
atestatementstoactualself-harm)andco-morbidpsy-
chiatricdisorders,suchasobsessive-compulsivedisor-
der(OCD)andattention-deficithyperactivitydisorder
∗Corresponding author: Dr. Andrea Eugenio Cavanna, MD, (ADHD)[4,5]. Largestudiesconductedbothinclinical
PhD.,DepartmentofNeuropsychiatry,TheBarberryNationalCen-
populations[2,6]andinthecommunity[7]havecon-
tre for Mental Health, 25 Vincent Drive, Birmingham B15 2FG,
sistentlyfoundthatonlyabout10%ofindividualswith
UK. Tel.: [phone]; Fax: [phone]; E-mail:
[email protected]. GTSdonotpresentwithbehaviouralco-morbidities.
ISSN0953-4180/13/$27.502013–IOSPressandtheauthors. Allrightsreserved
84 A.E.Cavannaetal./Health-relatedqualityoflifeinGillesdelaTourettesyndrome
Giventhe clinicalcomplexityof GTS,itisnotsur- ofthecombinationofticsandbehaviouralsymptoms.
prising that its impact would extend beyond physical Since diagnosisis oftenmadeyearsafter the onsetof
disability. Inanearlystudyexaminingfunctionalim- symptoms,patientswithGTScopewithdisruptive,un-
pairment in patients with GTS, Stefl found that 53% controlledsymptomswithoutunderstandingtheircause
of the participantshad soughtpsychotherapyto assist and often feel different from their peer group [22].
them in coping with the impact of their tics on dai- Moreover,mostpeoplewithGTStrytocamouflageor
ly functioning and a number of related problems, in- suppress their tics, at the expense of mounting inner
cludingstigma,anxietyanddepression[8]. Thisstudy tension,indicatingahighdegreeofself-consciousness.
firstshowedthatco-morbidbehaviouralandemotional Thibertetal. reportedthatadultswhosufferfromtics
problems are often the primary incentive for seeking and co-morbid obsessive-compulsive symptoms have
treatment. In a subsequentstudy, 88% of the sample altered ‘self-concepts’ and self-esteem and increased
reportedthatticsnegativelyinfluencedtheirdailyfunc- socialanxiety[23]. Accordingtotheseauthors’expe-
tioning[9]. Ithaslongbeenreportedthatpatientswith rience,acceptingandadaptingtoobviousticsymptoms
GTSexperiencedistressincopingwithticsintermsof is more difficultfor adults with co-morbidobsessive-
disruptionofdailyactivities[10,11],aswellasdifficul- compulsivesymptoms,whotendtobeperfectionistand
tieswithsocializing[12]. Thechronicpresenceoftics morepreoccupiedwiththeirownshortcomings.
andtic-associatedsymptomshasbeenshowntoaffect Adults with GTS also reporthigher rates of unem-
bothchildrenandadultswithGTS. ployment and lower income, since employment sta-
YoungpatientswithGTSoftenreportfunctionalim- tus largely depends on potential employers’ attitudes
pairments, defined as the inability to perform routine and other aspects of the social and cultural environ-
and age-appropriate tasks in the domains of school, ment[24].Furthermore,a high proportionof patients
home, and social activities [13,14]. It has been sug- with GTS report problems in cognitive functioning
gestedthatacomprehensiveassessmentofGTS-related (memory, concentration), which might explain poor
difficultiesinyoungpatientswithGTSshouldtakeinto academic achievement and therefore limited career
accountbothself-andproxy-reports,whichcandiffer choice, despite lack of evidence for major neuropsy-
substantially [15]. A study of 138 youths aged 5 to chologicalimpairment[25]. Overall,ithasbeenshown
18yearsshowedthat46%ofchildrenwithGTSdemon- thatpatientswithGTStendtobelongtoalowersocial
strate school-relatedproblems. Of note, patientswith classthantheirparents[26].
co-morbid ADHD had a nearly 4-fold increased risk
foracademicdifficultycomparedtothosewithoutAD-
HD[16]. Consistentfindingshaveshownthatmuchof 2. Studiesofhealthrelated-qualityoflifeinGilles
the psychosocialand behaviouraldysfunctionin chil- delaTourettesyndromepopulations
dren with tic disorders appears to be a consequence
ofco-morbidADHD,whichishighlyassociatedwith Healthrelated-qualityoflife(HR-QOL)hasbecome
disruptive behaviour and functional impairment [17– increasinglyrelevanttobothclinicalpractice(asatool
20]. Hoekstraetal.investigatedsocialandbehavioural for the identification of care needs) and research (as
problems related to ADHD, OCD and tic severity in apatient-reportedoutcomemeasure). HR-QOLisde-
childrenwithaticdisorder[21]. Inthisstudy,thepar- fined as the perceived physical, mental and social ef-
entsof58childrendiagnosedwitha tic disorderwith fectsofanillnessandassociatedtherapiesonapatient
and without different forms of ADHD were asked to over time [27], as opposed to the generic concept of
completemeasuresofbehaviouralproblems. Patients functionalimpairment.
withaticdisorderwithADHD-hyperactive/impulsive GTShasbeenshowntohaveasignificantimpacton
subtypehadthehighestquestionnairescores,subjects apatient’sHR-QOL,particularlythewidespreadeffect
with ADHD-inattentive subtype had medium scores across social and emotional domains [28]. By defi-
andsubjectswithoutADHDhadthelowestscores. The nition, HR-QOL is a subjective parameterand conse-
authorsconcludedthatinpatientswithticdisorders,the quentlydifficulttomeasureandquantify,howeverthere
presenceandseverityofADHDarethemainpredictors isaneedforsuchameasurementwhendevelopingand
ofbehaviouralandsocialproblems. assessingtheefficacyofinterventions. Recentstudies
Someproblemscanbecomeexacerbatedacrossthe ontheeffectivenessofneurosurgicalproceduresforse-
lifespan. Adults with moderate-to-severeGTS attract vere,treatment-resistantGTShavehighlightedtheim-
public attention due to the sometimes bizarre nature portanceoffocusingonHR-QOLasameasureofover-
A.E.Cavannaetal./Health-relatedqualityoflifeinGillesdelaTourettesyndrome 85
all patient satisfaction in outcome analysis. Relying population sample, but better HR-QOL than patients
solelyonchangesinticseveritydoesnotalwaysreflect withintractableepilepsy. Accordingtomultiplecom-
the patient’s overall well-being following neurosurgi- parisonanalysis,factorsinfluencingHR-QOLdomains
calinterventions. Forinstance,whenexploringtheef- inthisGTSsamplewereemploymentstatus,ticseveri-
fectivenessofinfrathalamicandthalamiclesioningfor ty,OCB,anxietyanddepression. Theauthorsconclud-
patientswithintractableGTS,Babel,etal.foundthata edthatHR-QOLinpatientswithGTSisimpairedand
reductioninticseveritydidnotcorrelatewithimproved thereforesuggestedthatself-reportHR-QOLmeasure-
patientsatisfaction[29]. Morerecently,Foltynieetal. mentsshouldbeusedalongsideconventionaloutcome
showed thatdeep brain stimulation (DBS) of the mo- measurementsinassessingtreatmentefficacy.
torportionof theglobuspallidus–parsinterna(GPi) Storchetal.examinedHR-QOLin59childrenand
mayresultinresolutionofticswithoutacorresponding adolescents (mean age 11.4 years; range 8–17 years)
improvementinHR-QOL,highlightingtheimportance diagnosed with GTS or chronic tic disorder and con-
of behavioural and psychological factors [30]. Both secutivelyreferredtoaspecialistclinic[28]. Ofthe59
studiesadvocatedtheuseofadisease-specificmeasure youths,16hadoneco-morbiddisorderand27hadmul-
ofHR-QOLasasurgicaloutcomemeasureinorderto tiple co-morbidities. Co-morbiddiagnoseswere AD-
accuratelyassesstheimpactoftreatmentandthemulti- HD(n =28),OCD(n =25),majordepressivedisor-
dimensionalfactorsaffectingapatient’sHR-QOL. der(n=6),generalizedanxietydisorder(n=7),op-
A systematic literature review of published studies positionaldefiantdisorder(n=6),Aspergersyndrome
of HR-QOL in GTS was conducted on the databas- (n=3),socialphobia(n=2)andpanicdisorder(n=
esPubMedandPsycInfo,using‘Tourette’,‘tics’, and 1). For all subjects, the authors collected tic severi-
‘qualityoflife’assearchterms. Fullarticles,including ty scores and parent-rated measures of the frequency
electronicearlyreleasepublications,wereobtainedand and intensity of behavioural and emotional problems
referenceswerecheckedforadditionalmaterialswhen exhibitedbytheirchildren(classifiedas‘internalizing’
appropriate. Thisliteraturereviewgenerated13stud- and‘externalizing’problems). Moreover,eachpatient
ies which specifically addressed HR-QOL in individ- completedthePediatricQualityofLifeinventory(Ped-
ualswith GTS: 9 studiesassessed HR-QOL in young sQL), a 23-item HR-QOL measure consisting of four
patientsand4studiesfocusedonadults. Thesestudies independentdomains(physical,emotional, socialand
are summarized in Table 1 and discussed in the fol- schoolfunctioning)combinedtoyieldphysical(equiv-
lowingparagraphs,inchronologicalorder. Twofurther alent to the physical functioning domain only), psy-
studies,dealingwiththedevelopmentandvalidationof chosocial(sum ofemotional,social, andschoolfunc-
thefirstdisease-specificHR-QOL scaleforGTS,will tioning domains) and total health scales (sum of all
bepresentedinaseparatesection. fourdomains)[34]. Thepatients’ parentswereasked
Elstneretal.interviewed103adultswithaDSM-III- to complete the PedsQL-Parent Proxy version. This
R-validated diagnosis of GTS from a specialist clinic studyyieldedfourmain findings. First, childrenwith
(meanage28.7years;range16–54years),ofwhom90 ticsexperiencedlowerHR-QOLthannon-clinicalsam-
completedstandardisedmeasuresofticseverity,OCD, ples in all areas except physical functioning, demon-
depressionandanxiety[31].HR-QOLwasassessedus- strating that the presence of tics has a negative im-
ingagenericinstrument,theMedicalOutcomesStudy pact on children’s lives. Specifically, children with
36-ItemShort-FormHealthSurvey(SF-36)[32],com- ticsratedtheirHR-QOLsimilarlytochildrenwithoth-
prising the following eight scales: physical function- er psychiatric disorders. Second, overall tic severity
ing, role limitation due to physicalfunctioning, bodi- was inversely associated with HR-QOL, possibly be-
lypain,socialfunctioning,rolelimitationduetoemo- causeticshaveadirectimpactonphysicalwell-being
tionalproblems,vitality,generalhealthperceptionand and/ordrawnegativeattentionbyothers. Third,parent-
mentalhealth. TheSF-36iscomplementedwithaself- child agreementin HR-QOL reportswas stronger for
evaluationofchangeinhealthoverthepastyear. HR- the youngerchildren (8–11 years) whereas these cor-
QOLwasalsoevaluatedusingtheQualityofLifeAs- relations were generally weaker for youths aged 12–
sessmentSchedule(QOLAS),ageneric,patient-driven 17years. Thisdifferencecouldbeexplainedbythefact
approachtoHR-QOLassessment,basedontheperson- thatparentsofyoungerchildrenmayspendmoretime
al construct theory and repertory grid technique [33]. with their children and/or communicate more regard-
BasedontheseHR-QOLmeasures,patientswithGTS ingtheirHR-QOL.Finally,internalizingandexternal-
showed significantly worse HR-QOL than a general izing behavioural symptoms were significantly relat-
86 A.E.Cavannaetal./Health-relatedqualityoflifeinGillesdelaTourettesyndrome
Mainlimitations 1.Referralbias2.Limitationsofinstruments(qualita-tiveandquantitativemeasures)3.Potentiallydifferentcopingstrate-giesbylong-standingandnewlydi-agnosedpatients 1.Samplesize2.Referralbias3.Limitationsofinstruments 1.Samplesize2.Referralbias3.Limitationsofinstruments(noself-reportmeasure) 1.Samplesize2.Referralbias3.Limitationsofinstruments 1.Samplesize2.Referralbias3.Limitationsofinstruments 1.Referralbias2.Limitationsofinstruments3.Nocontrolforco-morbidities 1.Referralbias2.Limitationsofinstruments3.Nocontrolforco-morbidities 1.Samplesize2.Referralbias3.Limitationsofinstruments4.VariablesaccountedforlimitedamountofvarianceinHR-QOLscore
QOLinGTSpopulations Mainfindings 1.HR-QOLinGTSwaspoorerthaninthegeneralpopulationbutbetterthanintheepilepsypopula-tion(normativedata)2.Depression,anxiety,OCB,ticseverityandem-ploymentstatuswereassociatedwithpoorHR-QOL 1.Ticseverityand‘internalizing’and‘externaliz-ing’behaviouralsymptomssignificantlycorrelat-edwithpoorHR-QOL2.Parent-childagreementinHR-QOLratingwasstrongerinchildren(age8–11)thanadolescents 1.OCDandADHD(inattentivesubtype)signifi-cantlycorrelatedwithpoorHR-QOL2.TicseveritydidnotcorrelatewithHR-QOL 1.HR-QOLinGTSwaspoorerthaninthegeneralpopulation(normativedata)2.Ticseverity,OCBandADHDcorrelatedwithpoorHR-QOL 1.HR-QOLinGTSwaspoorerthaninthegeneralpopulation,esp.inthefamilyactivitiesdomain(normativedata)2.Patientswithco-morbidconditionsreportedpoorerHR-QOLthanpatientswith‘pure’GTS 1.HR-QOLinGTSwaspoorerthaninHCbutbetterthaninLE2.GTS,MI,EPprovidedsimilarratingsforoverallHR-QOL3.GTSreportedbettersocialfunctioning,butworseemotional/schoolfunctioningthanMI/EP 1.HR-QOLinGTSwaspoorerthaninthegeneralpopulation(normativedata)2.Depression,ticseverityandagecorrelatedwithpoorHR-QOL 1.Depression,OCDandADHDcorrelatedwithpoorHR-QOL2.TicseveritydidnotcorrelatewithHR-QOL
Table1 dstudiesonHR- HR-QOLmeasure(type) QOLAS(interview-based)SF-36(self-report) PedsQL(self-report)PedsQL-ParentProxy(parent-report) TACQOL-PF(parent-report) PedsQL(self-report) CHQ(self-report) PedsQL4.0(self-report) EQ-5D(self-report) YQOL-R(self-report)
aryofpublishe Setting University-basedclinicforGTS University-basedclinicforticdisor-ders University-basedclinicforneurolog-icaldisorders University-basedclinicforGTS University-basedclinicsforGTS Twotriple-Apediatrichospitals Threeuniversity-basedclinicsforGTS University-basedclinicforGTS
Summ Diagnosis GTS(21.0%+GTSOCD) GTS/chronicticdisorder+(47.5%GTSADHD,42.4%+GTSOCD) GTS(64.3%+GTSADHD,8.9%+GTSOCD) GTS(31.6%+GTSADHD,17.5%+GTSOCD) GTS(56.3%+GTSADHD,40.8%+GTSOCD) GTS(NA) GTS(NA) GTS(52.0%+GTSADHD,48.0%+GTSOCD)
x
Meanage(range);Se 29(16–54)70M 11(8–17)41M 10(5–17)NA 11(8–17)46M 11(7–17)56M NA(8–12)293M 35(18–75)150M 13(10–17)44M
N 103 59 56 57 71 424+(618MI+250EP+42LE+1583HC) 200 50
A y
Country UK USA USA UK CanadaandUS China German Italy
Study Elstneretal.,2001[31] Storchetal.,2007[28] Bernardetal.,2009[35] Cutleretal.,2009[37] Pringsheimetal.,2009[38] Haoetal.,2010[39] ¨Muller-Vahletal.,2010[40] Eddyetal.,2011[43]
A.E.Cavannaetal./Health-relatedqualityoflifeinGillesdelaTourettesyndrome 87
Table1,continued MeanageDiagnosisSettingHR-QOLMainfindingsMainlimitations(range);Sexmeasure(type) 1.SamplesizeYQOL-R1.HR-QOLinGTSwaspoorerthaninthegeneralUniversity-13(10–17)GTS(52.0%+2.Referralbias(self-report)populationinspecificcontextualitems,butnotinbasedclinic44MGTS3.LimitationsofinstrumentsperceptualitemsforGTSADHD,48.0%+2.Thetypeofco-morbiditydeterminedwhichGTSOCD)HR-QOLdomainsweremostaffected(patientswith‘pure’GTSscoredlowerintheenvironmentdomain;patientswithGTS+OCDscoredlowerintheselfandrelationshipsdomain) Internet-PedsQL-SF151.Ticseverity,OCBandADHDcorrelatedwith1.Selectionbias(Internetaccessre-12(10–17)GTS/chronicbasedsurvey(self-report)poorHR-QOLquired)192Mticdisorder+2.Limitationsofinstruments(diag-(37.1%GTSnosesofticdisorders/co-morbiditiesADHD,39.2%+couldnotbeconfirmed)GTSOCD)3.Parentalinvolvementmayhaveaf-fectedyouthresponses >1.Selectionbias(Internetaccessre-PQOL1.TicseveritycorrelatedwithpoorHR-QOLInternet-18GTS/chronicquired)basedsurvey(self-report)2.Thecorrelationbetweenticseverityandfunc-ticdisorder2.Limitationsofinstrumentstionalimpairmentwasstrongerinthepresenceof(NA)(YGTSSdesignedtobeadministeredanxietyordepressionbyaclinicianratherthanself)3.Nocontrolforco-morbidities 1.Selectionbias(Internetaccessre-Internet-PQOL1.TicseveritycorrelatedwithpoorHR-QOL,psy-GTS/chronic35,5quired)basedsurvey(self-report)chologicaldifficultiesandgreaterdisabilityticdisorder(18–77)2.Limitationsofinstruments2.Positivecorrelationbetweenticseverityand(34.5%399M+(YGTSSdesignedtobeadministeredfunctionalimpairment3.Social/publicavoidanceOCD,byaclinicianratherthanself)andexperiencesofdiscriminationresultfromtics22.8%+ADHD,27,8%+MoodDisor-der,22,6%+AnxietyDis-order) University-GTS(54.3%23,91.SamplesizeGTS-QOL1.Ticseverity,premonitoryurgesandfamilyhis-+GTS(16–41)2.Referralbias(self-report)toryofGTSidentifiedaspredictorsduringchild-basedclinicADHD,30.4%41MhoodofapoorerHR-QOLinadultswithGTSforGTS+GTSOCD Questionnaire;EP,epilepsy;GTS,GillesdelaTourettesyndrome;HC,healthycontrols;HR-QOL,Healthrelatedqualityoflife;LE,leukemia;B,Obsessive-compulsivebehaviors;PedsQL,PediatricQualityofLifeInventory;PQOL,PerceivedQualityofLifeScale;QOLAS,QualityofLifeDisabilityScore;SF-36,MedicalOutcomesStudy36-ItemShort-FormHealthSurvey;TACQOL-PF,TNO-AZLChildren’sQualityofLifescale-Parentciation;YGTSS,YaleGlobalTicSeverityScale;YQOL-R,TheYouthQualityofLifeInstrument-Researchversion;GTS-QOL,GillesdelaTourette
StudyCountryN Eddyetal.,Italy50+2011[44](50EP+102HC) ConeleaetUSA232al.,2011[45] USA500Lewinetal.,2011[46] ConeleaetUSA672al.,2012[47] CavannaetUK46al.,2012[48] Abbreviations:CHQ,ChildHealthMI,migraine;NA,notavailable;OCAssessmentSchedule;SDS,SheehanForm;TSA,TouretteSyndromeAssoSyndrome-QualityofLifeScale.
88 A.E.Cavannaetal./Health-relatedqualityoflifeinGillesdelaTourettesyndrome
edtobothchild-andparent-ratedHR-QOL.However, sociallyacceptedandconformingtonormsareseenas
parent-ratedHR-QOL scores were generally lower in a challenge; the continuousstruggle to controltics to
childrenwithhighexternalizingsymptomsthaninchil- avoidembarrassmentcausessubjectivedistress;finally,
dren with low externalizing symptoms, thus showing theacceptanceofGTSaspartofwhatmakesthechil-
thatparentsarelikelytoviewexternalizingsymptoms drenwhotheyarecanposesignificantproblems. The
asmoreproblematicanddisruptivethantics. clinicalimplicationsofthisstudyincludebothtarget-
Bernard et al. assessed the association between tic ingco-morbiditiesforinterventionandrecognisingthat
severity, OCD, ADHD subtypes and HR-QOL in 56 encouraging children to accept their condition could
youngoutpatientswithadiagnosisofGTS(meanage minimizeemotionaldistress.
10 years; range 5–17 years) [35]. In this sample, Pringsheim et al. investigated how children with
36 patients had co-morbidADHD and 5 patients had GTS, with or without co-morbidities (ADHD and/or
co-morbid OCD. For each patient, tic severity, OCD OCD), experience disability [38]. Clinicians com-
andADHD ratingswerecollected. Thepatients’par- piled baseline information and symptom severity rat-
ents also completed the TNO-AZL Children’s Qual- ing scales, whilst parents completed a generic health
ity of Life scale-Parent Form (TACQOL-PF) [36], a statusmeasuredesignedspecificallyforchildrentoas-
genericHR-QOLmeasurewith56items,coveringsev- sess limitations, functional impairmentand participa-
en domains: Physical Complaints, Motor Function- tionrestrictionsaffectingbothphysicalandpsychoso-
ing, Autonomy, Cognitive Functioning, Social Func- cialhealth. Seventy-onechildren(meanage11years;
tioning,PositiveEmotions,NegativeEmotions. Inthe agerange7–17)recruitedattwospecialistclinicswere
TACQOL-PF, parents are asked to answer questions assignedtofoursubgroups: GTSonly(n =20),GTS
aboutthesedomainsfromtheperspectiveoftheirchild. +ADHD(n=22),GTS+ADHD+OCD(n=18),
Multipleregressionwasusedtoassesstherelationship and GTS + OCD (n = 11). Almost all psychosocial
between tic/OCD/ADHD ratings and HR-QOL. Ac- domain scores were significantly lower than national
cordingtotheresultsofunivariateanalysis,ticseverity norms for the GTS + ADHD and GTS + ADHD +
ratingswerenotassociatedwithHR-QOL.Ontheoth- OCD subgroups, whilst for the GTS only subgroup,
er hand, both ADHD and OCD were significantly re- onlythefamilyactivitiesdomainwassignificantlyaf-
latedtoHR-QOL.Specifically,sub-analysisofADHD fected. A multiple linear regression model including
subtypesshowedthatinattentiveness,butnothyperac- diagnosis, age, sex, and GTS/OCD/ADHD symptom
tivity,wasassociatedwithalowerHR-QOL.Whentic severity found that the most significant predictor of
severity,OCDandADHDwereconsideredsimultane- thepsychosocialsummaryscorewasADHDsymptom
ously, tic severity remained non-significant, whereas severity. TheauthorsconcludedthatchildrenwithGTS
bothADHDandOCDratingswerestatisticallysignif- +ADHD+/−OCDexperienceimpairmentinallas-
icant,indicatingthattheseco-morbidconditionswere pectsofpsychosocialhealth.
bothindependentcontributorstopoorerHR-QOL.The Haoetal. testedthe psychometricpropertiesofthe
authorsconcludedthatHR-QOLinchildrenwithGTS ChineseversionofthePedsQL4.0genericcorescales
relatesprimarilytoco-morbiditiesofOCDandADHD onarelativelylargesampleofpaediatricpatientswith
(predominantly inattentive symptoms), which should acuteand chronicconditionsencompassingGTS, mi-
beprioritisedwhenplanningtreatmentstrategies. graine, epilepsy, leukemia (n = 1335) and healthy
Cutleretal.investigatedtheeffectofGTSonthelives controls (n = 1583) [39]. The results of this study
of young patients, using both quantitative and quali- showedthatchildrenwithGTS,migraineandepilepsy
tative techniques [37]. Their sample of 57 children ratedtheiroverallHR-QOLasbetterthanpatientswith
(mean age 11.4 years; age range 8–17) was recruited leukemia,butworsethanhealthycontrols. Withinthe
froma specialistclinic. Co-morbidADHDwasdiag- psychosocialdomain,childrenwithGTSreportedbet-
nosedin18patients,whilst10patientshadco-morbid ter social functioning, but worse emotional or school
OCD. The PedsQL was used to assess HR-QOL. Da- functioning, than patients with migraine or epilepsy.
taanalysisrevealedthatsymptomseverity(definedas Accordingto the authors, their findingsprovidedrea-
the numberand frequencyof tics and the presence of sonableevidencetoshowthattheChinesePedsQL4.0
OCDandADHDsymptoms)wascorrelatedwithapoor has acceptable psychometric properties, with the ex-
HR-QOL. The qualitative analysis yielded four main ception of construct validity (tested by confirmatory
themes: theneedformanagingticsymptomshasaneg- factoranalysis)andinternalreliabilityforself-reportin
ative impact on a child’s HR-QOL; issues with being thepaediatricsampleswithGTSandmigraine.
A.E.Cavannaetal./Health-relatedqualityoflifeinGillesdelaTourettesyndrome 89
Mu¨ller-Vahletal.investigatedthecorrelatesofHR- sy (n = 50) and healthy controls (n = 102). Within
QOL in an adult population of patients with GTS in theGTSgroup,patientsweresubdividedaccordingto
Germany[40]. Theyassessed200patients(meanage presenceofco-morbidconditions: patientswith‘pure’
34.9 years; age range 18–75) using one of the most GTS(22%),patientswithGTSandADHD(30%),pa-
widely used generic measures of HR-QOL, the EQ- tientswithGTSandOCD(26%)andpatientswithboth
5D.TheEQ-5Dconsistsoffivedimensions(Mobility, co-morbidities(22%). ThepatientsintheGTSgroup
Self-Care,UsualActivities,Pain/DiscomfortandAnxi- were also classified into two groups according to the
ety/Depression),whichareratedonathree-pointscale: severity of their tics, as measured by the Yale Global
noproblems,someproblemsandextremeproblems. A Tic SeverityScale (YGTSS). The subgroupswere in-
visual analogue score (EQ-VAS) is also incorporated dependentlycomparedtothepatientswithepilepsyand
intothefinalEQ-5Dindexscore[41]. TheEQ-5Dhas thehealthycontrolsfortheHR-QOLscores. Increased
proven useful for the assessment of HR-QOL across ticseverityandthepresenceofco-morbiditieswereas-
movementdisorderscharacterizedbyneuropsychiatric sociatedwithapoorHR-QOL.Moreover,thepresence
symptoms,suchasParkinsondisease[42]. Theauthors of differentco-morbidities influenced which domains
ofthisstudyfoundthatincreasedticseverity,patient’s ofHR-QOLweremostaffected. Forexample,patients
ageandco-occurringdepressionwereassociatedwith with ‘pure’GTSscoredlowerin the environmentdo-
apoorerHR-QOL.However,therewerenodataavail- main, whilst patients with co-occurring OCD scored
ableonco-morbidADHDorOCD. lowerintheselfandrelationshipsdomain. Thesedif-
Eddy et al. enrolled 50 young people (mean age ficulties were more pronouncedin patients with GTS
13years;agerange10–17)withaDSM-IV-TRvalidat- compared to those with epilepsy or healthy controls.
eddiagnosisofGTStoinvestigatetheclinicalcorrelates Patientswith ‘pure’GTSalso exhibitedmoredepres-
ofHR-QOL[43]. Theseauthorsadministeredabattery sivesymptomscomparedtobothpatientswithepilepsy
ofsixstandardizedpsychometricmeasuresalongwith andcontrols.
agenericHR-QOLquestionnaire,theYouthQualityof Coneleaetal. conducteda largeinternet-basedsur-
LifeInstrument-Researchversion(YQOL-R),consist- vey involving 740 parents with children with chronic
ingof‘perceptual’and‘contextual’items. The41per- ticdisorders(CTD)and232childrenintheyouthsam-
ceptualitems addressthe patients’ perceptionof their ple (mean age 12 years; age range 10–17) [45]. The
HR-QOL across four specific domains: the self do- TouretteSyndromeImpactSurveyforChildren(TSIS-
main, the relationships domain, the environment do- C)wasdevelopedspecificallyforthisstudyinorderto
mainandthegeneralQOLdomain. Theseitemstack- gatherdataonthefunctionalimpactoflivingwithCTD
le issues ranging from how patients feel about them- from both parent and child perspectives. The parent
selves, to their relationshipswith peersand the world andyouthsectionsofthesurvey-generateddatacould
they live in. The 15 contextual items are of a more be classified into five domains: physical, social, fa-
objectivenature,relatingtospecificaspectsoflifethat milial,academic,andpsychological. Theauthorsused
canaffectHR-QOL.Multiplestepwiseregressionanal- the PedsQL to evaluate HR-QOL, along with a stan-
ysisrevealedthatthemeasuresassessingthepresence dardizedbattery of questionnairesto assess tics, anx-
ofOCD,ADHDanddepressionwerethestrongestpre- iety, depression and family impact. According to the
dictorsofHR-QOL.Interestingly,ticseveritywasnot presenceofco-morbidconditions,thesamplewascat-
significantlyassociatedwithHR-QOL. egorizedintoCTD-Onlypatients(parentsampleCTD-
Eddyetal.alsoconductedtheonlycontrolledstudy Only: n = 361, youth sample CTD-Only: n = 107)
specificallyaddressingHR-QOLinGTStodate,com- andCTD-Pluspatients(parentsampleCTD-Plus: n=
paring the HR-QOL of young people with GTS with 375, youthsample CTD-Plus: n = 125). Co-morbid
thatofpatientswithepilepsyandhealthysubjects[44]. behavioural problems included: ADHD, OCD, anxi-
In lightof the controversyin previousresearch, these ety disorders, depression, disruptive behaviour disor-
authors further examined whether tic severity or the ders, bipolar disorder, somatoform disorder, learning
presenceofco-morbiditieshasagreaterbearingonper- disabilities, eatingdisorders,pervasivedevelopmental
ceivedHR-QOL.TheYQOL-RwasusedtoassessHR- disorders, trichotillomaniaand mentalretardation. In
QOL,asintheirpreviousstudy. Atotalof202young accordance with previous studies, both increased tic
peoplewererecruited(meanage12.9years;agerange severityandthepresenceofco-morbidpsychiatricdis-
10–17) and divided into three groups: patients with orders were associated with a poorer HR-QOL and
GTS(n =50),patientswithbenignidiopathicepilep- greaterfunctionalimpairment. Moreover,the authors
90 A.E.Cavannaetal./Health-relatedqualityoflifeinGillesdelaTourettesyndrome
foundthat childrenwith GTS experiencemarkeddis- 3. TheGTS-QOL:Adisease-specificHR-QOL
criminationduetotheirtics. Anxiety,depressionand measure
family functioning difficulties were also found to be
more prevalent in this population than in the general Albeit heterogeneous in methodology and sample
population. sizes, the reviewed studies show that HR-QOL is
Lewinetal.expandedontheworkbyConeleaetal. emerging as a critical measure of clinical outcome
intheirinternet-basedsurveyof500adultpatientswith as it takes into account the patient’s own subjective
CTD to investigate whether the relationship between view [49]. Disease-specific HR-QOL measures have
tic severity and both functionalimpairmentand QOL been developed for patients suffering from neuropsy-
wasmoderatedbythepresenceofanxietyanddepres- chiatricconditionsbearingsimilaritiestoGTS,includ-
sion [46]. The authorsfound a strong correlationbe- ing cervicaldystonia[50]and hemifacialspasm [51].
tweenticseverityandfunctionalimpairment,especial- However,untilrecently,therehasbeennotooltomea-
ly in patients suffering from anxiety and depression. sureGTS-specificHR-QOL.
Conversely,wherepatientsscoredlessonanxietyand The GTS-QOL [52] was developedto fill this gap.
depression scales, there was a weaker association be- Thedevelopmentandvalidationprocess,whichinclud-
tween tic severity and functional impairment. It was edalargefield-testonasampleof136patientsrecruit-
suggestedthatacombinationoftherapiestargetingboth edthroughtheUKTourettesAction,resultedinaclin-
ticsandanxiety/depressionmayimproveoutcomes. icallymeaningfulandpsychometricallysound27-item
Coneleaetal.exploredthefunctionalimpactoftics instrumentformeasuringHR-QOLinadultswithGTS.
in adults using a sample of 672 participants with a Specifically,thescalesatisfiedstandardcriteriaforac-
self-reported CTD (mean age 35,5 years; range 18– ceptability,convergentanddiscriminantvalidity,inter-
77 years). They assessed the impact of tics on phys- nalconsistencyandtest-retestreliability. Theitemsof
ical, social, occupational/academic, and psychologi- theGTS-QOLaregroupedintofourdomains(psycho-
cal functioning using the Tourette Syndrome Impact logical,physical,obsessive-compulsiveandcognitive)
Survey(TSISScale)andtheSheehanDisabilityScale andtheinstrumentiscomplementedwithavisualana-
(SDS). Global functioning and quality of life was al- loguescale(VAS)ratingoverallsatisfactionwithlife.
so evaluatedusingthe PQOL.Results suggestedmild ThedomainsanditemsoftheGTS-QOLareshownin
tomoderatefunctionalimpairmentandpositivecorre- Table2.
lations between tic severity and impairment. Notable TheGTS-QOLhasthepotentialtocomplementboth
portions of the sample reported also social or public clinical rating scales and generic HR-QOL measures.
avoidanceandexperiencesofdiscriminationresulting Thesetwotypesoftraditionalassessmentshavesignifi-
from tics. Compared to previously reported popula- cantlimitationsasclinicaltoolsandoutcomemeasures.
tion norms, participants had more psychological dif- Bydefinition,assessmentofdiseaseseverityusingclin-
ficulties, greater disability, and poorer quality of life. ical rating scales omits patient views about issues of
The presence of motor tics interfering with voluntary importanceto their health, particularlyemotionaland
behaviourwasidentifiedasthestrongestpredictorfor cognitivefunctioningandthesubjectiveimpactofdys-
disability,QOLandpsychologicaldifficulties[47]. functionondailylife. Ofnote,ithasbeenshownthat
Finally, Cavanna et al. investigated the childhood perceptionofpatients’HR-QOLbyphysiciansandpa-
predictors of HR-QOL in a cohort of adult patients tients themselves can substantially diverge from each
with GTS. In this study 46 patients with GTS aged 6 other [53]. Generic HR-QOL instruments do not in-
to16yearsunderwentabaselinestandardisedclinical corporate, and are unlikely to be sensitive to specific
assessment of both tics and behaviouralsymptoms at featureswhicharecentraltopatientswithGTS(motor
a specialist GTS clinic. The same patients were re- andvocaltics,tic-relatedsymptoms),andarelikelyto
assessedaged16yearsandabove,withameanfollow- underestimatehealthproblemsinGTS.Therefore,the
up period of 13 years (range 3–25 years), using the GTS-QOLmayproveusefulnotonlytoevaluateHR-
GillesdelaTouretteSyndrome–QualityofLifeScale QOL in individual patients but also in epidemiologi-
(GTS-QOL), a disease-specific measure of HR-QOL. calandobservationaltrialsandtorelateneuroimaging
The results of the multiple linear regression analysis orpathophysiologicalfindingstosubjectiveperception
showedthatticseverity,premonitoryurgesandfamily ofHR-QOL.Inclinicalpractice,thisinstrumentholds
historyofGTScouldbeidentifiedaspredictorsduring promise as an outcome measure in longitudinal stud-
childhoodofapoorerHR-QOLinadultswithGTS[48]. iesandclinicaltrialsoftreatmentstrategies,including
A.E.Cavannaetal./Health-relatedqualityoflifeinGillesdelaTourettesyndrome 91
Table2
pactonHR-QOL.Specifically,theseverityofticsand
Domains and items of the disease-specific Gilles de la Tourette
presenceofco-morbidities,particularlyOCDandAD-
Syndrome-QualityofLifescale(GTS-QOL)
HD,areassociatedwithapoorerHR-QOLinchildren.
Domain Items
It is therefore important that clinicians routinely as-
Psychological – Anxiety
sess patients to determine which aspects of HR-QOL
– Depressedmood
– Difficultyseeingfriends aremostaffectedarethereforerequireattentionregard-
– Frustration ing planning treatment. A similar picture exists for
– Lackofcontroloverownlife
adults, where depression and anxiety also contribute
– Lackofself-confidence
– Lackofsocialsupport tooverallHR-QOL.Disease-specificinstruments,such
– Loneliness/isolation as the GTS-QOL, capture all relevantaspects of HR-
– Moodswitches QOLandthusshouldberegardedasimportantoutcome
– Restlessness
measuresfortherapeuticinterventionsandusefultools
– Temperdiscontrol
in developingappropriatecare plans for patientswith
Physical/ADL – Difficultyinactivitiesofdailyliving
GTS.Importantly,theGTS-QOLincludesasubjective
– Difficultytakingpartinsocialactivi-
ties patientperceptionofHR-QOLwhichcanbeinterpret-
– Embarrassinggestures edinlightoftheobjectivedisabilityscoresinorderto
– Involuntaryswearing
helpplanpatient-centeredcare.
– Movementdiscontrol
– Painorinjuries This paper reviewed the recent literature on HR-
– Phonictics QOLinGTS,spanningonedecade. Thereviewedev-
Obsessive-compulsive – Concernsaboutpoorhealth idence has significant limitations as the studies differ
– Copyingpeople in research methodology. For example, different in-
– Repeatingactions
strumentswereusedtoassessHR-QOL,noneofwhich
– Repeatingwords
were disease-specific; therefore, the results of each
– Unpleasantthoughts
studymaybeskewedtothefocusofagiveninstrument.
Cognitive – Difficultyconcentrating
– Difficultyfinishingtasks Themeansofdatacollectiondiffersvastlyfromclini-
– Losingimportantthings calseriestointernetsurveysandthereforethisreview
– Memoryproblems is limited in the cohesiveness with which the results
canbecollated. Itisalsounclearhowthestudiesaccu-
behavioural therapies, medications and neurosurgical rately diagnose co-morbidityand whether the criteria
procedures. for such a diagnosis are comparable across different
TheGTS-QOLhasrecentlybeenadaptedtothechild studies. Furthermore,participantsinvolvedinthestud-
andadolescentpopulationwithGTS[54]. Theprocess iesweremostlyrecruitedfromtertiaryreferralcentres,
ofbacktranslation,languageadaptationandscaleval- whichattractmorecomplexcases,oftenwithmultiple
idationhasledtothedevelopmentoftwoinstruments, co-morbidities. Asaconsequenceofreferralbias,the
whicharesuitableforuse inchildrenandadolescents study samples may notbe a generalizablerepresenta-
with GTS, respectively (GTS-QOL-C&A). The psy- tionofthecommunitypopulationofpatientswithGTS
chometricpropertiesoftheseinstrumentshaveproven andthusmaynotreflecttheinfluencesonHR-QOLin
satisfactoryin a field test on childrenandadolescents the average patient. Some of the studies used proxy
recruitedatthreespecialGTScentresinItaly. Theval- HR-QOLmeasureswherebyparentsratedtheirchild’s
idationoftheGTS-QOL-C&AinEnglishlanguageis HR-QOL,thusintroducingafurtheraccuracybias[15].
currentlyongoing. Storchetal.,forexample,showedthattheparent-child
agreementintheadolescentgroupwaspoorlycorrelat-
ed [28]. The paucity of studies in children and ado-
4. Preliminaryconclusionsandsuggestionsfor lescentspresentsa problemsince this disorderhasits
futureresearch onsetinchildhood. Theissueofbothlackofchildhood
studies and small sample sizes could be addressed in
GTS is a lifelong disorder which causes functional future research by studying a community sample and
impairment,disability,andpsychologicaldistress. The reporting on the HR-QOL from a truly large sample
results of the reviewed studies suggest that the broad acrossallages. Furthermore,biaseswithinthesample
clinicalpictureof GTSshouldbeaddressedwhenas- existduetolimitationsinaccesstocareandtherelative
sessingthepatient’sandfamily’sperceptionofitsim- paucityof practitionerswho are skilled in diagnosing
92 A.E.Cavannaetal./Health-relatedqualityoflifeinGillesdelaTourettesyndrome
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