83
Behavioural Neurology 27 (2013) 83–93
DOI 10.3233/BEN-120296
IOS Press
Review Article
Health-related quality of life in Gilles de la
Tourette syndrome: A decade of research
Andrea Eugenio Cavannaa,b,∗, Kate Davidb , Valentina Banderac, Cristiano Terminec,
Umberto Balottind , Anette Schraga,e and Caroline Selaia
a
Sobell Department of Movement Disorders, Institute of Neurology and University College London, London, UK
Department of Neuropsychiatry, BSMHFT and University of Birmingham, Birmingham, UK
c
Child Neuropsychiatry Unit, Department of Experimental Medicine, University of Insubria, Varese, Italy
d
Department of Child Neurology and Psychiatry, IRCCS ‘C. Mondino’ Foundation, University of Pavia, Pavia, Italy
e
Department of Neurology, Royal Free and University College Medical School, London, UK
b
Abstract. Gilles de la Tourette syndrome (GTS) is a neurodevelopmental condition characterised by multiple motor and phonic
tics and associated behavioural problems, carrying a significant burden on patients’ lives. Although the term health related-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-QOL affected by GTS and, if so, in what domains?” by conducting a systematic literature review of published original studies
addressing HR-QOL in both children and adult patients with GTS. This review focuses on the current evidence on the impact of
GTS on patients’ lives, mainly informed by studies using generic functional impairment and HR-QOL measures from the last
decade, and expands on the new opportunities introduced by the recently developed GTS-specific HR-QOL scales (GTS-QOL
and GTS-QOL-C&A). Analysis of the first decade of studies specifically addressing HR-QOL in GTS suggests that co-morbid
conditions are key factors in determining HR-QOL in young patients, whilst the picture is more complex in adults with GTS.
These findings offer some general directions for both current clinical practice and future research.
Keywords: Gilles de la Tourette syndrome, health-related quality of life, functional impairment, tics, behavioural problems
1. The functional impact of Gilles de la Tourette
syndrome across the lifespan
Gilles de la Tourette syndrome (GTS) is a life-long
neurodevelopmental disorder defined by the presence
of multiple motor and phonic tics [1]. Tics are repetitive, uncontrollable movements or vocalizations that
usually present in childhood but may change with re-
∗ Corresponding author: Dr. Andrea Eugenio Cavanna, MD,
PhD., Department of Neuropsychiatry, The Barberry National Centre for Mental Health, 25 Vincent Drive, Birmingham B15 2FG,
UK. Tel.: +44 0121 3012317; Fax: +44 0121 3012291; E-mail:
cavanna77@tin.it.
gard to their location, frequency and severity over
time [2]. GTS affects approximately 1% of school-age
youngsters and is three to four times more common
in males than females [3]. GTS is increasingly recognised as a complex disorder, with a wide spectrum of
associated behavioural problems that can accompany
the motor and phonic tics. These problems include ticrelated symptoms (ranging from socially inappropriate statements to actual self-harm) and co-morbid psychiatric disorders, such as obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder
(ADHD) [4,5]. Large studies conducted both in clinical
populations [2,6] and in the community [7] have consistently found that only about 10% of individuals with
GTS do not present with behavioural co-morbidities.
ISSN 0953-4180/13/$27.50 2013 – IOS Press and the authors. All rights reserved
84
A.E. Cavanna et al. / Health-related quality of life in Gilles de la Tourette syndrome
Given the clinical complexity of GTS, it is not surprising that its impact would extend beyond physical
disability. In an early study examining functional impairment in patients with GTS, Stefl found that 53%
of the participants had sought psychotherapy to assist
them in coping with the impact of their tics on daily functioning and a number of related problems, including stigma, anxiety and depression [8]. This study
first showed that co-morbid behavioural and emotional
problems are often the primary incentive for seeking
treatment. In a subsequent study, 88% of the sample
reported that tics negatively influenced their daily functioning [9]. It has long been reported that patients with
GTS experience distress in coping with tics in terms of
disruption of daily activities [10,11], as well as difficulties with socializing [12]. The chronic presence of tics
and tic-associated symptoms has been shown to affect
both children and adults with GTS.
Young patients with GTS often report functional impairments, defined as the inability to perform routine
and age-appropriate tasks in the domains of school,
home, and social activities [13,14]. It has been suggested that a comprehensive assessment of GTS-related
difficulties in young patients with GTS should take into
account both self- and proxy-reports, which can differ
substantially [15]. A study of 138 youths aged 5 to
18 years showed that 46% of children with GTS demonstrate school-related problems. Of note, patients with
co-morbid ADHD had a nearly 4-fold increased risk
for academic difficulty compared to those without ADHD [16]. Consistent findings have shown that much of
the psychosocial and behavioural dysfunction in children with tic disorders appears to be a consequence
of co-morbid ADHD, which is highly associated with
disruptive behaviour and functional impairment [17–
20]. Hoekstra et al. investigated social and behavioural
problems related to ADHD, OCD and tic severity in
children with a tic disorder [21]. In this study, the parents of 58 children diagnosed with a tic disorder with
and without different forms of ADHD were asked to
complete measures of behavioural problems. Patients
with a tic disorder with ADHD-hyperactive/impulsive
subtype had the highest questionnaire scores, subjects
with ADHD-inattentive subtype had medium scores
and subjects without ADHD had the lowest scores. The
authors concluded that in patients with tic disorders, the
presence and severity of ADHD are the main predictors
of behavioural and social problems.
Some problems can become exacerbated across the
lifespan. Adults with moderate-to-severe GTS attract
public attention due to the sometimes bizarre nature
of the combination of tics and behavioural symptoms.
Since diagnosis is often made years after the onset of
symptoms, patients with GTS cope with disruptive, uncontrolled symptoms without understanding their cause
and often feel different from their peer group [22].
Moreover, most people with GTS try to camouflage or
suppress their tics, at the expense of mounting inner
tension, indicating a high degree of self-consciousness.
Thibert et al. reported that adults who suffer from tics
and co-morbid obsessive-compulsive symptoms have
altered ‘self-concepts’ and self-esteem and increased
social anxiety [23]. According to these authors’ experience, accepting and adapting to obvious tic symptoms
is more difficult for adults with co-morbid obsessivecompulsive symptoms, who tend to be perfectionist and
more preoccupied with their own shortcomings.
Adults with GTS also report higher rates of unemployment and lower income, since employment status largely depends on potential employers’ attitudes
and other aspects of the social and cultural environment [24]. Furthermore, a high proportion of patients
with GTS report problems in cognitive functioning
(memory, concentration), which might explain poor
academic achievement and therefore limited career
choice, despite lack of evidence for major neuropsychological impairment [25]. Overall, it has been shown
that patients with GTS tend to belong to a lower social
class than their parents [26].
2. Studies of health related-quality of life in Gilles
de la Tourette syndrome populations
Health related-quality of life (HR-QOL) has become
increasingly relevant to both clinical practice (as a tool
for the identification of care needs) and research (as
a patient-reported outcome measure). HR-QOL is defined as the perceived physical, mental and social effects of an illness and associated therapies on a patient
over time [27], as opposed to the generic concept of
functional impairment.
GTS has been shown to have a significant impact on
a patient’s HR-QOL, particularly the widespread effect
across social and emotional domains [28]. By definition, HR-QOL is a subjective parameter and consequently difficult to measure and quantify, however there
is a need for such a measurement when developing and
assessing the efficacy of interventions. Recent studies
on the effectiveness of neurosurgical procedures for severe, treatment-resistant GTS have highlighted the importance of focusing on HR-QOL as a measure of over-
A.E. Cavanna et al. / Health-related quality of life in Gilles de la Tourette syndrome
all patient satisfaction in outcome analysis. Relying
solely on changes in tic severity does not always reflect
the patient’s overall well-being following neurosurgical interventions. For instance, when exploring the effectiveness of infrathalamic and thalamic lesioning for
patients with intractable GTS, Babel, et al. found that a
reduction in tic severity did not correlate with improved
patient satisfaction [29]. More recently, Foltynie et al.
showed that deep brain stimulation (DBS) of the motor portion of the globus pallidus – pars interna (GPi)
may result in resolution of tics without a corresponding
improvement in HR-QOL, highlighting the importance
of behavioural and psychological factors [30]. Both
studies advocated the use of a disease-specific measure
of HR-QOL as a surgical outcome measure in order to
accurately assess the impact of treatment and the multidimensional factors affecting a patient’s HR-QOL.
A systematic literature review of published studies
of HR-QOL in GTS was conducted on the databases PubMed and PsycInfo, using ‘Tourette’, ‘tics’, and
‘quality of life’ as search terms. Full articles, including
electronic early release publications, were obtained and
references were checked for additional materials when
appropriate. This literature review generated 13 studies which specifically addressed HR-QOL in individuals with GTS: 9 studies assessed HR-QOL in young
patients and 4 studies focused on adults. These studies
are summarized in Table 1 and discussed in the following paragraphs, in chronological order. Two further
studies, dealing with the development and validation of
the first disease-specific HR-QOL scale for GTS, will
be presented in a separate section.
Elstner et al. interviewed 103 adults with a DSM-IIIR-validated diagnosis of GTS from a specialist clinic
(mean age 28.7 years; range 16–54 years), of whom 90
completed standardised measures of tic severity, OCD,
depression and anxiety [31]. HR-QOL was assessed using a generic instrument, the Medical Outcomes Study
36-Item Short-Form Health Survey (SF-36) [32], comprising the following eight scales: physical functioning, role limitation due to physical functioning, bodily pain, social functioning, role limitation due to emotional problems, vitality, general health perception and
mental health. The SF-36 is complemented with a selfevaluation of change in health over the past year. HRQOL was also evaluated using the Quality of Life Assessment Schedule (QOLAS), a generic, patient-driven
approach to HR-QOL assessment, based on the personal construct theory and repertory grid technique [33].
Based on these HR-QOL measures, patients with GTS
showed significantly worse HR-QOL than a general
85
population sample, but better HR-QOL than patients
with intractable epilepsy. According to multiple comparison analysis, factors influencing HR-QOL domains
in this GTS sample were employment status, tic severity, OCB, anxiety and depression. The authors concluded that HR-QOL in patients with GTS is impaired and
therefore suggested that self-report HR-QOL measurements should be used alongside conventional outcome
measurements in assessing treatment efficacy.
Storch et al. examined HR-QOL in 59 children and
adolescents (mean age 11.4 years; range 8–17 years)
diagnosed with GTS or chronic tic disorder and consecutively referred to a specialist clinic [28]. Of the 59
youths, 16 had one co-morbid disorder and 27 had multiple co-morbidities. Co-morbid diagnoses were ADHD (n = 28), OCD (n = 25), major depressive disorder (n = 6), generalized anxiety disorder (n = 7), oppositional defiant disorder (n = 6), Asperger syndrome
(n = 3), social phobia (n = 2) and panic disorder (n =
1). For all subjects, the authors collected tic severity scores and parent-rated measures of the frequency
and intensity of behavioural and emotional problems
exhibited by their children (classified as ‘internalizing’
and ‘externalizing’ problems). Moreover, each patient
completed the Pediatric Quality of Life inventory (PedsQL), a 23-item HR-QOL measure consisting of four
independent domains (physical, emotional, social and
school functioning) combined to yield physical (equivalent to the physical functioning domain only), psychosocial (sum of emotional, social, and school functioning domains) and total health scales (sum of all
four domains) [34]. The patients’ parents were asked
to complete the PedsQL-Parent Proxy version. This
study yielded four main findings. First, children with
tics experienced lower HR-QOL than non-clinical samples in all areas except physical functioning, demonstrating that the presence of tics has a negative impact on children’s lives. Specifically, children with
tics rated their HR-QOL similarly to children with other psychiatric disorders. Second, overall tic severity
was inversely associated with HR-QOL, possibly because tics have a direct impact on physical well-being
and/or draw negative attention by others. Third, parentchild agreement in HR-QOL reports was stronger for
the younger children (8–11 years) whereas these correlations were generally weaker for youths aged 12–
17 years. This difference could be explained by the fact
that parents of younger children may spend more time
with their children and/or communicate more regarding their HR-QOL. Finally, internalizing and externalizing behavioural symptoms were significantly relat-
86
Table 1
Summary of published studies on HR-QOL in GTS populations
Study
Country
N
Mean age
Diagnosis
Setting
(range); Sex
29 (16–54) GTS (21.0% University70 M
GTS + OCD) based clinic
for GTS
Main findings
Main limitations
1.HR-QOL in GTS was poorer than in the general
population but better than in the epilepsy population (normative data)
2.Depression, anxiety, OCB, tic severity and employment status were associated with poor HRQOL
1.Referral bias
2.Limitations of instruments (qualitative and quantitative measures)
3.Potentially different coping strategies by long-standing and newly diagnosed patients
PedsQL
(self-report)
PedsQL-Parent
Proxy (parentreport)
1.Tic severity and ‘internalizing’ and ‘externaliz- 1.Sample size
ing’ behavioural symptoms significantly correlat- 2.Referral bias
3.Limitations of instruments
ed with poor HR-QOL
2.Parent-child agreement in HR-QOL rating was
stronger in children (age 8–11) than adolescents
Elstner et al., UK
2001 [31]
103
Storch et al., USA
2007 [28]
59
11 (8–17)
41 M
GTS/chronic
tic disorder
(47.5% GTS +
ADHD, 42.4%
GTS + OCD)
Universitybased clinic
for tic disorders
Bernard et
USA
al., 2009 [35]
56
10 (5–17)
NA
GTS (64.3%
GTS +
ADHD, 8.9%
GTS + OCD)
University- TACQOL-PF
based clinic (parent-report)
for neurological disorders
Cutler et al., UK
2009 [37]
57
11 (8–17)
46 M
GTS (31.6% Universitybased clinic
GTS +
ADHD, 17.5% for GTS
GTS + OCD)
PedsQL
(self-report)
1.HR-QOL in GTS was poorer than in the general 1.Sample size
2.Referral bias
population (normative data)
2.Tic severity, OCB and ADHD correlated with 3.Limitations of instruments
poor HR-QOL
11 (7–17)
56 M
GTS (56.3% University- CHQ
based clinics (self-report)
GTS +
ADHD, 40.8% for GTS
GTS + OCD)
1.HR-QOL in GTS was poorer than in the general 1.Sample size
population, esp. in the family activities domain 2.Referral bias
3.Limitations of instruments
(normative data)
2.Patients with co-morbid conditions reported
poorer HR-QOL than patients with ‘pure’ GTS
1.OCD and ADHD (inattentive subtype) signifi- 1.Sample size
2.Referral bias
cantly correlated with poor HR-QOL
2. Tic severity did not correlate with HR-QOL 3.Limitations of instruments (no selfreport measure)
Pringsheim
et al.,
2009 [38]
Canada
and USA
71
Hao et al.,
2010 [39]
China
NA (8–12)
424
(+618 MI 293 M
+250 EP
+42 LE
+1583HC)
GTS (NA)
Two triple-A PedsQL 4.0
(self-report)
pediatric
hospitals
1.HR-QOL in GTS was poorer than in HC but 1.Referral bias
2.Limitations of instruments
better than in LE
2.GTS, MI, EP provided similar ratings for overall 3.No control for co-morbidities
HR-QOL
3.GTS reported better social functioning, but
worse emotional/school functioning than MI/EP
Müller-Vahl Germany
et al.,
2010 [40]
200
35 (18–75)
150 M
GTS (NA)
EQ-5D
Three
(self-report)
universitybased clinics
for GTS
1.HR-QOL in GTS was poorer than in the general 1.Referral bias
2.Limitations of instruments
population (normative data)
2.Depression, tic severity and age correlated with 3.No control for co-morbidities
poor HR-QOL
Eddy et al.,
2011 [43]
50
13 (10–17)
44 M
GTS (52.0% Universitybased clinic
GTS +
ADHD, 48.0% for GTS
GTS + OCD)
Italy
YQOL-R
(self-report)
1.Depression, OCD and ADHD correlated with 1.Sample size
2.Referral bias
poor HR-QOL
3.Limitations of instruments
2.Tic severity did not correlate with HR-QOL
4.Variables accounted for limited
amount of variance in HR-QOL score
A.E. Cavanna et al. / Health-related quality of life in Gilles de la Tourette syndrome
HR-QOL
measure (type)
QOLAS
(interviewbased)
SF-36
(self-report)
Table 1, continued
Study
Country
N
Eddy et al.,
2011 [44]
Italy
50
(+ 50 EP
+102 HC)
Mean age
Diagnosis
(range); Sex
13 (10–17) GTS (52.0%
44 M
GTS +
ADHD, 48.0%
GTS + OCD)
Setting
Universitybased clinic
for GTS
Main limitations
1.Sample size
2.Referral bias
3.Limitations of instruments
Conelea et
USA
al., 2011 [45]
232
12 (10–17)
192 M
PedsQL-SF15
GTS/chronic Internetbased survey (self-report)
tic disorder
(37.1% GTS +
ADHD, 39.2%
GTS + OCD)
Lewin et al., USA
2011 [46]
500
> 18
GTS/chronic
tic disorder
(NA)
InternetPQOL
based survey (self-report)
1.Tic severity correlated with poor HR-QOL
2.The correlation between tic severity and functional impairment was stronger in the presence of
anxiety or depression
1.Selection bias (Internet access required)
2.Limitations of instruments
(YGTSS designed to be administered
by a clinician rather than self)
3.No control for co-morbidities
Conelea et
USA
al., 2012 [47]
672
35,5
(18–77)
399 M
PQOL
GTS/chronic Internetbased survey (self-report)
tic disorder
(34.5%
+OCD,
22.8%
+ADHD,
27,8%
+Mood Disorder,
22,6%
+Anxiety Disorder )
1.Tic severity correlated with poor HR-QOL, psychological difficulties and greater disability
2.Positive correlation between tic severity and
functional impairment 3.Social/public avoidance
and experiences of discrimination result from tics
1.Selection bias (Internet access required)
2.Limitations of instruments
(YGTSS designed to be administered
by a clinician rather than self)
Cavanna et UK
al., 2012 [48]
46
23,9
(16–41)
41 M
GTS (54.3% UniversityGTS +
based clinic
ADHD, 30.4% for GTS
GTS + OCD
1.Tic severity, premonitory urges and family his- 1.Sample size
tory of GTS identified as predictors during child- 2.Referral bias
hood of a poorer HR-QOL in adults with GTS
GTS-QOL
(self-report)
1.Tic severity, OCB and ADHD correlated with 1.Selection bias (Internet access repoor HR-QOL
quired)
2.Limitations of instruments (diagnoses of tic disorders/co-morbidities
could not be confirmed)
3.Parental involvement may have affected youth responses
87
Abbreviations: CHQ, Child Health Questionnaire; EP, epilepsy; GTS, Gilles de la Tourette syndrome; HC, healthy controls; HR-QOL, Health related quality of life; LE, leukemia;
MI, migraine; NA, not available; OCB, Obsessive-compulsive behaviors; PedsQL, Pediatric Quality of Life Inventory; PQOL, Perceived Quality of Life Scale; QOLAS, Quality of Life
Assessment Schedule; SDS, Sheehan Disability Score; SF-36, Medical Outcomes Study 36-Item Short-Form Health Survey; TACQOL-PF, TNO-AZL Children’s Quality of Life scale-Parent
Form; TSA, Tourette Syndrome Association; YGTSS, Yale Global Tic Severity Scale; YQOL-R, The Youth Quality of Life Instrument-Research version; GTS-QOL, Gilles de la Tourette
Syndrome-Quality of Life Scale.
A.E. Cavanna et al. / Health-related quality of life in Gilles de la Tourette syndrome
HR-QOL
Main findings
measure (type)
YQOL-R
1.HR-QOL in GTS was poorer than in the general
(self-report)
population in specific contextual items, but not in
perceptual items
2.The type of co-morbidity determined which
HR-QOL domains were most affected (patients
with ‘pure’ GTS scored lower in the environment
domain; patients with GTS+OCD scored lower in
the self and relationships domain)
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A.E. Cavanna et al. / Health-related quality of life in Gilles de la Tourette syndrome
ed to both child- and parent-rated HR-QOL. However,
parent-rated HR-QOL scores were generally lower in
children with high externalizing symptoms than in children with low externalizing symptoms, thus showing
that parents are likely to view externalizing symptoms
as more problematic and disruptive than tics.
Bernard et al. assessed the association between tic
severity, OCD, ADHD subtypes and HR-QOL in 56
young outpatients with a diagnosis of GTS (mean age
10 years; range 5–17 years) [35]. In this sample,
36 patients had co-morbid ADHD and 5 patients had
co-morbid OCD. For each patient, tic severity, OCD
and ADHD ratings were collected. The patients’ parents also completed the TNO-AZL Children’s Quality of Life scale-Parent Form (TACQOL-PF) [36], a
generic HR-QOL measure with 56 items, covering seven domains: Physical Complaints, Motor Functioning, Autonomy, Cognitive Functioning, Social Functioning, Positive Emotions, Negative Emotions. In the
TACQOL-PF, parents are asked to answer questions
about these domains from the perspective of their child.
Multiple regression was used to assess the relationship
between tic/OCD/ADHD ratings and HR-QOL. According to the results of univariate analysis, tic severity
ratings were not associated with HR-QOL. On the other hand, both ADHD and OCD were significantly related to HR-QOL. Specifically, sub-analysis of ADHD
subtypes showed that inattentiveness, but not hyperactivity, was associated with a lower HR-QOL. When tic
severity, OCD and ADHD were considered simultaneously, tic severity remained non-significant, whereas
both ADHD and OCD ratings were statistically significant, indicating that these co-morbid conditions were
both independent contributors to poorer HR-QOL. The
authors concluded that HR-QOL in children with GTS
relates primarily to co-morbidities of OCD and ADHD
(predominantly inattentive symptoms), which should
be prioritised when planning treatment strategies.
Cutler et al. investigated the effect of GTS on the lives
of young patients, using both quantitative and qualitative techniques [37]. Their sample of 57 children
(mean age 11.4 years; age range 8–17) was recruited
from a specialist clinic. Co-morbid ADHD was diagnosed in 18 patients, whilst 10 patients had co-morbid
OCD. The PedsQL was used to assess HR-QOL. Data analysis revealed that symptom severity (defined as
the number and frequency of tics and the presence of
OCD and ADHD symptoms) was correlated with a poor
HR-QOL. The qualitative analysis yielded four main
themes: the need for managing tic symptoms has a negative impact on a child’s HR-QOL; issues with being
socially accepted and conforming to norms are seen as
a challenge; the continuous struggle to control tics to
avoid embarrassment causes subjective distress; finally,
the acceptance of GTS as part of what makes the children who they are can pose significant problems. The
clinical implications of this study include both targeting co-morbidities for intervention and recognising that
encouraging children to accept their condition could
minimize emotional distress.
Pringsheim et al. investigated how children with
GTS, with or without co-morbidities (ADHD and/or
OCD), experience disability [38]. Clinicians compiled baseline information and symptom severity rating scales, whilst parents completed a generic health
status measure designed specifically for children to assess limitations, functional impairment and participation restrictions affecting both physical and psychosocial health. Seventy-one children (mean age 11 years;
age range 7–17) recruited at two specialist clinics were
assigned to four subgroups: GTS only (n = 20), GTS
+ ADHD (n = 22), GTS + ADHD + OCD (n = 18),
and GTS + OCD (n = 11). Almost all psychosocial
domain scores were significantly lower than national
norms for the GTS + ADHD and GTS + ADHD +
OCD subgroups, whilst for the GTS only subgroup,
only the family activities domain was significantly affected. A multiple linear regression model including
diagnosis, age, sex, and GTS/OCD/ADHD symptom
severity found that the most significant predictor of
the psychosocial summary score was ADHD symptom
severity. The authors concluded that children with GTS
+ ADHD +/− OCD experience impairment in all aspects of psychosocial health.
Hao et al. tested the psychometric properties of the
Chinese version of the PedsQL 4.0 generic core scales
on a relatively large sample of paediatric patients with
acute and chronic conditions encompassing GTS, migraine, epilepsy, leukemia (n = 1335) and healthy
controls (n = 1583) [39]. The results of this study
showed that children with GTS, migraine and epilepsy
rated their overall HR-QOL as better than patients with
leukemia, but worse than healthy controls. Within the
psychosocial domain, children with GTS reported better social functioning, but worse emotional or school
functioning, than patients with migraine or epilepsy.
According to the authors, their findings provided reasonable evidence to show that the Chinese PedsQL 4.0
has acceptable psychometric properties, with the exception of construct validity (tested by confirmatory
factor analysis) and internal reliability for self-report in
the paediatric samples with GTS and migraine.
A.E. Cavanna et al. / Health-related quality of life in Gilles de la Tourette syndrome
Müller-Vahl et al. investigated the correlates of HRQOL in an adult population of patients with GTS in
Germany [40]. They assessed 200 patients (mean age
34.9 years; age range 18–75) using one of the most
widely used generic measures of HR-QOL, the EQ5D. The EQ-5D consists of five dimensions (Mobility,
Self-Care, Usual Activities, Pain/Discomfort and Anxiety/Depression), which are rated on a three-point scale:
no problems, some problems and extreme problems. A
visual analogue score (EQ-VAS) is also incorporated
into the final EQ-5D index score [41]. The EQ-5D has
proven useful for the assessment of HR-QOL across
movement disorders characterized by neuropsychiatric
symptoms, such as Parkinson disease [42]. The authors
of this study found that increased tic severity, patient’s
age and co-occurring depression were associated with
a poorer HR-QOL. However, there were no data available on co-morbid ADHD or OCD.
Eddy et al. enrolled 50 young people (mean age
13 years; age range 10–17) with a DSM-IV-TR validated diagnosis of GTS to investigate the clinical correlates
of HR-QOL [43]. These authors administered a battery
of six standardized psychometric measures along with
a generic HR-QOL questionnaire, the Youth Quality of
Life Instrument-Research version (YQOL-R), consisting of ‘perceptual’ and ‘contextual’ items. The 41 perceptual items address the patients’ perception of their
HR-QOL across four specific domains: the self domain, the relationships domain, the environment domain and the general QOL domain. These items tackle issues ranging from how patients feel about themselves, to their relationships with peers and the world
they live in. The 15 contextual items are of a more
objective nature, relating to specific aspects of life that
can affect HR-QOL. Multiple stepwise regression analysis revealed that the measures assessing the presence
of OCD, ADHD and depression were the strongest predictors of HR-QOL. Interestingly, tic severity was not
significantly associated with HR-QOL.
Eddy et al. also conducted the only controlled study
specifically addressing HR-QOL in GTS to date, comparing the HR-QOL of young people with GTS with
that of patients with epilepsy and healthy subjects [44].
In light of the controversy in previous research, these
authors further examined whether tic severity or the
presence of co-morbidities has a greater bearing on perceived HR-QOL. The YQOL-R was used to assess HRQOL, as in their previous study. A total of 202 young
people were recruited (mean age 12.9 years; age range
10–17) and divided into three groups: patients with
GTS (n = 50), patients with benign idiopathic epilep-
89
sy (n = 50) and healthy controls (n = 102). Within
the GTS group, patients were subdivided according to
presence of co-morbid conditions: patients with ‘pure’
GTS (22%), patients with GTS and ADHD (30%), patients with GTS and OCD (26%) and patients with both
co-morbidities (22%). The patients in the GTS group
were also classified into two groups according to the
severity of their tics, as measured by the Yale Global
Tic Severity Scale (YGTSS). The subgroups were independently compared to the patients with epilepsy and
the healthy controls for the HR-QOL scores. Increased
tic severity and the presence of co-morbidities were associated with a poor HR-QOL. Moreover, the presence
of different co-morbidities influenced which domains
of HR-QOL were most affected. For example, patients
with ‘pure’ GTS scored lower in the environment domain, whilst patients with co-occurring OCD scored
lower in the self and relationships domain. These difficulties were more pronounced in patients with GTS
compared to those with epilepsy or healthy controls.
Patients with ‘pure’ GTS also exhibited more depressive symptoms compared to both patients with epilepsy
and controls.
Conelea et al. conducted a large internet-based survey involving 740 parents with children with chronic
tic disorders (CTD) and 232 children in the youth sample (mean age 12 years; age range 10–17) [45]. The
Tourette Syndrome Impact Survey for Children (TSISC) was developed specifically for this study in order to
gather data on the functional impact of living with CTD
from both parent and child perspectives. The parent
and youth sections of the survey-generated data could
be classified into five domains: physical, social, familial, academic, and psychological. The authors used
the PedsQL to evaluate HR-QOL, along with a standardized battery of questionnaires to assess tics, anxiety, depression and family impact. According to the
presence of co-morbid conditions, the sample was categorized into CTD-Only patients (parent sample CTDOnly: n = 361, youth sample CTD-Only: n = 107)
and CTD-Plus patients (parent sample CTD-Plus: n =
375, youth sample CTD-Plus: n = 125). Co-morbid
behavioural problems included: ADHD, OCD, anxiety disorders, depression, disruptive behaviour disorders, bipolar disorder, somatoform disorder, learning
disabilities, eating disorders, pervasive developmental
disorders, trichotillomania and mental retardation. In
accordance with previous studies, both increased tic
severity and the presence of co-morbid psychiatric disorders were associated with a poorer HR-QOL and
greater functional impairment. Moreover, the authors
90
A.E. Cavanna et al. / Health-related quality of life in Gilles de la Tourette syndrome
found that children with GTS experience marked discrimination due to their tics. Anxiety, depression and
family functioning difficulties were also found to be
more prevalent in this population than in the general
population.
Lewin et al. expanded on the work by Conelea et al.
in their internet-based survey of 500 adult patients with
CTD to investigate whether the relationship between
tic severity and both functional impairment and QOL
was moderated by the presence of anxiety and depression [46]. The authors found a strong correlation between tic severity and functional impairment, especially in patients suffering from anxiety and depression.
Conversely, where patients scored less on anxiety and
depression scales, there was a weaker association between tic severity and functional impairment. It was
suggested that a combination of therapies targeting both
tics and anxiety/depression may improve outcomes.
Conelea et al. explored the functional impact of tics
in adults using a sample of 672 participants with a
self-reported CTD (mean age 35,5 years; range 18–
77 years). They assessed the impact of tics on physical, social, occupational/academic, and psychological functioning using the Tourette Syndrome Impact
Survey (TSIS Scale) and the Sheehan Disability Scale
(SDS). Global functioning and quality of life was also evaluated using the PQOL. Results suggested mild
to moderate functional impairment and positive correlations between tic severity and impairment. Notable
portions of the sample reported also social or public
avoidance and experiences of discrimination resulting
from tics. Compared to previously reported population norms, participants had more psychological difficulties, greater disability, and poorer quality of life.
The presence of motor tics interfering with voluntary
behaviour was identified as the strongest predictor for
disability, QOL and psychological difficulties [47].
Finally, Cavanna et al. investigated the childhood
predictors of HR-QOL in a cohort of adult patients
with GTS. In this study 46 patients with GTS aged 6
to 16 years underwent a baseline standardised clinical
assessment of both tics and behavioural symptoms at
a specialist GTS clinic. The same patients were reassessed aged 16 years and above, with a mean followup period of 13 years (range 3–25 years), using the
Gilles de la Tourette Syndrome – Quality of Life Scale
(GTS-QOL), a disease-specific measure of HR-QOL.
The results of the multiple linear regression analysis
showed that tic severity, premonitory urges and family
history of GTS could be identified as predictors during
childhood of a poorer HR-QOL in adults with GTS [48].
3. The GTS-QOL: A disease-specific HR-QOL
measure
Albeit heterogeneous in methodology and sample
sizes, the reviewed studies show that HR-QOL is
emerging as a critical measure of clinical outcome
as it takes into account the patient’s own subjective
view [49]. Disease-specific HR-QOL measures have
been developed for patients suffering from neuropsychiatric conditions bearing similarities to GTS, including cervical dystonia [50] and hemifacial spasm [51].
However, until recently, there has been no tool to measure GTS-specific HR-QOL.
The GTS-QOL [52] was developed to fill this gap.
The development and validation process, which included a large field-test on a sample of 136 patients recruited through the UK Tourettes Action, resulted in a clinically meaningful and psychometrically sound 27-item
instrument for measuring HR-QOL in adults with GTS.
Specifically, the scale satisfied standard criteria for acceptability, convergent and discriminant validity, internal consistency and test-retest reliability. The items of
the GTS-QOL are grouped into four domains (psychological, physical, obsessive-compulsive and cognitive)
and the instrument is complemented with a visual analogue scale (VAS) rating overall satisfaction with life.
The domains and items of the GTS-QOL are shown in
Table 2.
The GTS-QOL has the potential to complement both
clinical rating scales and generic HR-QOL measures.
These two types of traditional assessments have significant limitations as clinical tools and outcome measures.
By definition, assessment of disease severity using clinical rating scales omits patient views about issues of
importance to their health, particularly emotional and
cognitive functioning and the subjective impact of dysfunction on daily life. Of note, it has been shown that
perception of patients’ HR-QOL by physicians and patients themselves can substantially diverge from each
other [53]. Generic HR-QOL instruments do not incorporate, and are unlikely to be sensitive to specific
features which are central to patients with GTS (motor
and vocal tics, tic-related symptoms), and are likely to
underestimate health problems in GTS. Therefore, the
GTS-QOL may prove useful not only to evaluate HRQOL in individual patients but also in epidemiological and observational trials and to relate neuroimaging
or pathophysiological findings to subjective perception
of HR-QOL. In clinical practice, this instrument holds
promise as an outcome measure in longitudinal studies and clinical trials of treatment strategies, including
A.E. Cavanna et al. / Health-related quality of life in Gilles de la Tourette syndrome
Table 2
Domains and items of the disease-specific Gilles de la Tourette
Syndrome-Quality of Life scale (GTS-QOL)
Domain
Psychological
Items
– Anxiety
– Depressed mood
– Difficulty seeing friends
– Frustration
– Lack of control over own life
– Lack of self-confidence
– Lack of social support
– Loneliness/isolation
– Mood switches
– Restlessness
– Temper discontrol
Physical/ADL
– Difficulty in activities of daily living
– Difficulty taking part in social activities
– Embarrassing gestures
– Involuntary swearing
– Movement discontrol
– Pain or injuries
– Phonic tics
Obsessive-compulsive
–
–
–
–
–
Concerns about poor health
Copying people
Repeating actions
Repeating words
Unpleasant thoughts
Cognitive
–
–
–
–
Difficulty concentrating
Difficulty finishing tasks
Losing important things
Memory problems
behavioural therapies, medications and neurosurgical
procedures.
The GTS-QOL has recently been adapted to the child
and adolescent population with GTS [54]. The process
of back translation, language adaptation and scale validation has led to the development of two instruments,
which are suitable for use in children and adolescents
with GTS, respectively (GTS-QOL-C&A). The psychometric properties of these instruments have proven
satisfactory in a field test on children and adolescents
recruited at three special GTS centres in Italy. The validation of the GTS-QOL-C&A in English language is
currently ongoing.
4. Preliminary conclusions and suggestions for
future research
GTS is a lifelong disorder which causes functional
impairment, disability, and psychological distress. The
results of the reviewed studies suggest that the broad
clinical picture of GTS should be addressed when assessing the patient’s and family’s perception of its im-
91
pact on HR-QOL. Specifically, the severity of tics and
presence of co-morbidities, particularly OCD and ADHD, are associated with a poorer HR-QOL in children.
It is therefore important that clinicians routinely assess patients to determine which aspects of HR-QOL
are most affected are therefore require attention regarding planning treatment. A similar picture exists for
adults, where depression and anxiety also contribute
to overall HR-QOL. Disease-specific instruments, such
as the GTS-QOL, capture all relevant aspects of HRQOL and thus should be regarded as important outcome
measures for therapeutic interventions and useful tools
in developing appropriate care plans for patients with
GTS. Importantly, the GTS-QOL includes a subjective
patient perception of HR-QOL which can be interpreted in light of the objective disability scores in order to
help plan patient-centered care.
This paper reviewed the recent literature on HRQOL in GTS, spanning one decade. The reviewed evidence has significant limitations as the studies differ
in research methodology. For example, different instruments were used to assess HR-QOL, none of which
were disease-specific; therefore, the results of each
study may be skewed to the focus of a given instrument.
The means of data collection differs vastly from clinical series to internet surveys and therefore this review
is limited in the cohesiveness with which the results
can be collated. It is also unclear how the studies accurately diagnose co-morbidity and whether the criteria
for such a diagnosis are comparable across different
studies. Furthermore, participants involved in the studies were mostly recruited from tertiary referral centres,
which attract more complex cases, often with multiple
co-morbidities. As a consequence of referral bias, the
study samples may not be a generalizable representation of the community population of patients with GTS
and thus may not reflect the influences on HR-QOL in
the average patient. Some of the studies used proxy
HR-QOL measures whereby parents rated their child’s
HR-QOL, thus introducing a further accuracy bias [15].
Storch et al., for example, showed that the parent-child
agreement in the adolescent group was poorly correlated [28]. The paucity of studies in children and adolescents presents a problem since this disorder has its
onset in childhood. The issue of both lack of childhood
studies and small sample sizes could be addressed in
future research by studying a community sample and
reporting on the HR-QOL from a truly large sample
across all ages. Furthermore, biases within the sample
exist due to limitations in access to care and the relative
paucity of practitioners who are skilled in diagnosing
92
A.E. Cavanna et al. / Health-related quality of life in Gilles de la Tourette syndrome
and treating systems of the disorder in ways that are
supported by evidence.
Analysis of the first decade of studies specifically
addressing HR-QOL in GTS suggests some general directions for future research. An interesting preliminary observation is that whilst co-morbid conditions
appear to play a central role in determining HR-QOL in
younger patients, the picture is more complex in adults
with GTS. Possible reasons for this trend could be
the natural course of common neurodevelopmental comorbidities such as ADHD, which spontaneously improves with age, and the development of copying strategies for behavioural problems through adolescence and
early adulthood. Ascertainment bias could also be partly responsible for these observations, as adult patients
attending specialist clinics for GTS, rather than general
psychiatry clinics, are more likely to be seeking help
for the management of severe tics. These findings offer
some general directions for both current clinical practice and future research. Cross-sectional studies are
now abundant and therefore future research needs to focus on longitudinal studies to determine how the natural
history of GTS and patient adaptation and adjustment
may influence changes in HR-QOL from childhood to
adulthood. Future studies might build on what has
been learned from the limitations of each of the studies
described here and how these papers have moved the
field forward. Future research should also explore the
use of the newly developed disease-specific measures
of HR-QOL (GTS-QOL and GTS-QOL-C&A) for the
assessment of both clinic and community patients with
GTS.
Acknowledgments
The authors are grateful to Tourette Syndrome
Association-USA and Tourettes Action-UK for continuing support. VB was funded by COST-Action
BM0905.
Conflicts of interest
The authors have no conflicts of interest to declare.
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