Jeremy S. Stern

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce.

European clinical guidelines for Tourette Syndrome and other tic disorders. Part I: assessment

A working group of the European Society for the Study of Tourette Syndrome (ESSTS) has developed the first European assessment guidelines of Tourette Syndrome (TS). The available literature including national guidelines was thoroughly screened and extensively discussed in the expert group of ESSTS members. Detailed clinical assessment guidelines of tic disorders and their comorbidities in both children and adults are presented. Screening methods that might be helpful and necessary for specialists’ differential diagnosis process are suggested in order to further analyse cognitive abilities, emotional functions and motor skills. Besides clinical interviews and physical examination, additional specific tools (questionnaires, checklists and neuropsychological tests) are recommended.

Dissecting the Gilles de la Tourette spectrum: a factor analytic study on 639 patients

Background Recent studies using quantitative methods, such as principal component factor analysis, hierarchical cluster analysis and latent class analysis have suggested that Gilles de la Tourette syndrome (GTS) should no longer be considered a unitary condition as in current classification systems. Objective To identify quantitative components of GTS symptomatology using a large, well characterised cohort of singleton individuals with GTS in order to inform future genetic studies with more homogeneous phenotypes. Methods Principal component factor analysis with oblique rotation was used to analyse symptom data from a sample of 639 patients recruited at two tertiary referral centres using identical schedules during the period 1980–2008. Results Three Factors were identified: (1) complex motor tics and echo-paliphenomena; (2) attention deficit and hyperactivity symptoms plus aggressive behaviours; and (3) complex vocal tics and coprophenomena. Obsessive compulsive behaviours loaded significantly on the first two factors. The three factors accounted for 48.5% of the total symptomatic variance. Conclusions GTS is a phenotypically heterogeneous condition encompassing simple tics, specific complex tics and associated behavioural problems. The results, coupled with previous findings, identified a clinical continuum of complex tics, hyperactivity/impulsivity symptoms and semantically relevant utterances and gestures. A better characterisation of the GTS phenotypes will help to identify susceptibility genes.

Coprophenomena in Tourette syndrome.

The aims of this descriptive study were to examine the prevalence and associations of coprophenomena (involuntary expression of socially unacceptable words or gestures) in individuals with Tourette syndrome. Participant data were obtained from the Tourette Syndrome International Database Consortium. A specialized data collection form was completed for each of a subset of 597 consecutive new patients with Tourette syndrome from 15 sites in seven countries. Coprolalia occurred at some point in the lifetime of 19.3% of males and 14.6% of females, and copropraxia in 5.9% of males and 4.9% of females. Coprolalia was three times as frequent as copropraxia, with a mean onset of each at about 11 years, 5 years after the onset of tics. In 11% of those with coprolalia and 12% of those with copropraxia these coprophenomena were one of the initial symptoms of Tourette syndrome. The onsets of tics, coprophenomena, smelling of non‐food objects, and spitting were strongly intercorrelated. Early onset of coprophenomena was not associated with its longer persistence. The most robust associations of coprophenomena were with the number of non‐tic repetitive behaviors, spitting, and inappropriate sexual behavior. Although coprophenomena are a frequently feared possibility in the course of Tourette syndrome, their emergence occurs in only about one in five referred patients. Because the course and actual impact of coprophenomena are variable, additional prospective research is needed to provide better counseling and prognostic information.

Premonitory urges for tics in adult patients with Tourette syndrome

OBJECTIVE Patients with Tourette syndrome (TS) often report characteristic sensory experiences, also called premonitory urges (PUs), which precede tic expression and have high diagnostic relevance. This study investigated the usefulness of a scale developed and validated in children and adolescents-the Premonitory Urge for Tics Scale (PUTS, Woods et al., 2005 [13])-for the assessment of PUs in adult patients with TS. METHOD Standard statistical methods were applied to test the psychometric properties of the PUTS in 102 adult TS outpatients recruited from two specialist clinics in the United Kingdom. RESULTS The PUTS showed good acceptability and endorsement rates, with evenly distributed scores and low floor and ceiling effects. Item-total correlations were moderate to strong; PUTS total scores were significantly correlated with quantitative measures of TS severity. The PUTS showed excellent internal consistency reliability (Cronbachs alpha=0.85) and Spearmans correlations demonstrated satisfactory convergent and discriminant validity. CONCLUSIONS Although originally devised to assess urges to tic in young patients with TS, the PUTS demonstrated good psychometric properties in a large sample of adults recruited at specialist TS clinics. This instrument is therefore recommended for use across the life span as a valid and reliable self-report measure of sensory experiences accompanying tic expression.

Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway

We report here that alpha‐lipoic acid (α‐LA), a naturally‐occurring antioxidant, scavenges reactive oxygen species (ROS) followed by an increase in apoptosis of human hepatoma cells. Apoptosis induced by α‐LA was dependent upon the activation of the caspase cascade and the mitochondrial death pathway. α‐LA induced increases in caspase‐9 and caspase‐3 but had no significant effect on caspase‐8 activity. Apoptosis induced by α‐LA was found to be mediated through the tensin homologue deleted on chromosome 10 (PTEN)/Akt pathway. Prior to cell apoptosis, PTEN was activated and its downstream target Akt was inhibited. Our findings indicate that increasing ROS scavenging could be a therapeutic strategy to treat cancer.

Tic disorders: new developments in Tourette syndrome and related disorders.

The constellation of motor and vocal tics and certain of the other neuropsychiatric symptoms seen in Tourette syndrome are thought to have an organic basis, although the nature of the neurobiological lesion is uncertain. The syndrome is usually familial but the presumed genetic substrate has not been identified. A number of models currently under debate include a proposed autoimmune contribution.

TICS ASSOCIATED WITH AUTISTIC AND PERVASIVE DEVELOPMENTAL DISORDERS

Coincident cases of Tourette syndrome and Pervasive Developmental Disorders increasingly have been reported in the literature. Coincident cases currently number around 90. A minority of cases have been associated with cases of Tourette syndrome and tics in other family members; this has led some authors to suggest that Tourette syndrome may be responsible for some of the genetic heterogeneity in Pervasive Developmental Disorders. The literature is reviewed, along with some aspects of the neurobiology of the two conditions with arguments for and against this hypothesis.

Emotional processing and executive functioning in children and adults with Tourette's syndrome

Tourettes syndrome (TS) is predominantly a childhood disorder, with many of those who meet diagnostic criteria in childhood experiencing a remission of symptoms in adulthood. This indicates that the influence of TS on cognitive and emotional processing can best be understood by examining performance in both adults and children with TS. The present study examined emotional processing using a battery of face and prosody tasks with increasing levels of difficulty (same-different emotion discrimination, emotion naming, and emotion naming with conflict for prosody only). Experiment 1 compared the performance of children with TS-alone (n = 16) or TS+ADHD (n = 15) to healthy matched control children (n = 27). Compared to healthy control children, no significant group differences were found for those with TS-alone. Children with TS+ADHD showed subtle impairments on the more difficult emotion processing tasks relative to healthy control children, and differences were more pronounced for anger items (voice emotion naming, p < .05; voice emotion naming with conflict, p < .01). Experiment 2 compared the performance of adults with TS-alone (n = 23) to healthy matched controls (n = 21). No significant group differences were found, other than evidence of subtle impairment in the adults with TS-alone on the most complex task, again particularly for anger items (p < .05). Separate measurement of executive skills detected no evidence of impairment in children or adults with TS and little in the way of correlational evidence linking emotion recognition and executive skills. Implications of the findings for our understanding of emotion processing in TS are discussed.

Perceptions of treatment for tics among young people with Tourette syndrome and their parents: a mixed methods study

BackgroundTourette syndrome (TS) among young people is associated with psychosocial difficulties and parents play an important role in the management of the condition. Clinical guidelines have been developed for the treatment of TS and tics, but little is known about how young people and their parents perceive their treatment options or their desired outcomes of treatment. The aim of this study is to explore perceptions of treatments for tics among young people with TS and their parents.MethodsIn-depth interviews with 42 young people with TS and a mixed-methods, online survey of 295 parents of young people with TS. Participant recruitment was conducted through Tourettes Action (TA): a non-profit UK organisation for the support of people with TS. Interview transcripts were analysed using thematic analysis and responses to survey open-ended questions were analysed using content analysis. Triangulation of qualitative and quantitative data from the parents’ survey and qualitative data from the interviews with young people was used to increase the validity and depth of the findings.ResultsA strong theme was the perception that health professionals have limited knowledge of TS and its treatment. Medication was a common treatment for tics and both young people and parents described benefits of medication. However, adverse effects were frequently described and these were a common reason for stopping medication among young people. Aripiprazole was viewed most positively. Access to behavioural interventions for tics was limited and 76% of parents wanted this treatment to be available for their child. Some young people had reservations about the effectiveness or practicality of behavioural interventions. Reduction and abolition of tics were desired outcomes of treatment, but both parents and young people also identified the importance of increasing control over tics and reducing anxiety-related symptoms. For young people, managing the urge to tic was an important outcome of treatment.ConclusionsThe results suggest a need for more training in the identification and management of TS and wider availability of behavioural treatments. Clinical trials could explore the effectiveness of Aripiprazole used in combination with psycho-educational interventions to reduce anxiety and promote a sense of control.