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This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD (n = 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42, p < 0.01). There was no association between 25(OH)D and tic severity. However, a 10 ng/ml increase in 25(OH)D was associated with lower odds of having comorbid ADHD within the CTD cohort (OR 0.55, 95% CI 0.36–0.84, p = 0.01) and was inversely associated with ADHD symptom severity (β = − 2.52, 95% CI − 4.16–0.88, p < 0.01). In conclusion, lower vitamin D levels were not associated with a higher presence or severity of tics but were associated with the presence and severity of comorbid ADHD in children and adolescents with CTD. [ABSTRACT FROM AUTHOR]

Background: There is clear evidence that tic disorders (TDs) are associated with psychosocial stress as well as emotional and behavioral problems. Studies have shown that individuals with TDs have higher acute physiological stress responses to external, single stressors (as reflected by saliva cortisol). The aim of the present study was to examine a physiological marker of longer-term stress (as reflected by hair cortisol concentration) in children and adolescents with TDs and unaffected siblings of individuals with TDs. Methods: Two samples of a European cohort were included in this study. In the COURSE sample, 412 children and adolescents aged 3–16 years with a chronic TD including Tourette syndrome according to DSM IV-TR criteria were included. The ONSET sample included 131 3–10 years old siblings of individuals with TDs, who themselves had no tics. Differences in hair cortisol concentration (HCC) between the two samples were examined. Within the COURSE sample, relations of HCC with tic severity and perceived psychosocial stress as well as potential effects and interaction effects of comorbid emotional and behavioral problems and psychotropic medication on HCC were investigated. Results: There were no differences in HCC between the two samples. In participants with TDs, there were no associations between HCC and tic severity or perceived psychosocial stress. No main effects of sex, psychotropic medication status and comorbid emotional and behavioral problems on HCC were found in participants with TDs. Conclusion: A link between HCC and TDs is not supported by the present results. [ABSTRACT FROM AUTHOR]

Little is known about the long-term prognosis of children with pediatric acute-onset neuropsychiatric syndrome (PANS). Out of the 46 eligible patients from the Karolinska PANS cohort, 34 consented to participate in a follow-up (median 3.3 years). Participants underwent a thorough clinical evaluation and were classified according to their clinical course. Resulting groups were compared on clinical characteristics and laboratory test results. We observed significant reductions in clinician-rated PANS symptom severity and improved general function. Two patients were classified as remitted, 20 as relapsing–remitting, and 12 as having a chronic-static/progressive course. The latter group had an earlier onset, greater impairment and received more pharmacological and psychological treatments. Although remission was rare, the majority of children with PANS were significantly improved over the follow-up period but a non-negligible minority of patients displayed a chronic-static/progressive course and required additional treatments. The proposed definitions of flare and clinical course may be useful in future clinical trials. [ABSTRACT FROM AUTHOR]

This study examined predictors of, and associations between, self-concept, demographic variables, and clinical measures in fifty-eight children and adolescents with Persistent Tic Disorder (PTD; 44 males, Mage = 11.9 years, SD = 2.74). Participants completed measures that assessed self-concept, tic severity, tic-related impairment, and comorbid psychological symptoms. Results showed that generalized anxiety disorder, major depressive disorder, persistent depressive disorder, total tic severity, number and complexity of tics, and total and social tic-related impairment were associated with self-concept. Tic-related social impairment mediated the relationship between tic severity and self-concept. Exploratory analyses found that total tic severity, motor tic severity, and vocal tic severity, as well as the number, intensity, and interference of tics predicted social tic-related impairment. Results suggest that treatments to reduce the number and complexity of tics, with additional focus on navigating social interactions, may serve to decrease tic severity and impairment, and in turn, improve self-concept. [ABSTRACT FROM AUTHOR]

We compared anxiety symptoms in youth with and without tic disorders by comparing scores on the Multidimensional Anxiety Scale for Children (MASC) in youth with tic disorders to those in a concurrent community control group and in a group of treatment-seeking anxious youth from the Child/Adolescent Anxiety Multimodal Study (CAMS). Data from 176 youth with tic disorders, 93 control subjects, and 488 CAMS participants were included. Compared to youth with tic disorders, controls had lower total MASC scores (p < 0.0001) and CAMS participants had similar total MASC scores (p = 0.13). Separation Anxiety (p = 0.0003) and Physical Symptom (p < 0.0001) subscale scores were higher in youth with tic disorders than in CAMS participants. We conclude that the anxiety symptom profile differs in youth with and without tic disorders, which may have important implications for targeting treatment of anxiety in youth with tic disorders. [ABSTRACT FROM AUTHOR]

Tics are unique from most movement disorders, in that they are partially suppressible. As part of the inhibitory motor network, the pre-supplementary motor area is engaged in motor control and may be involved in tic physiology. We used dual-site transcranial magnetic stimulation to assess inhibitory connectivity between right pre-supplementary motor area and left primary motor cortex, which has previously been demonstrated in healthy adults. We also used diffusion tensor imaging to investigate white matter connectivity in children with chronic tics. Twelve children with chronic tic disorder and fourteen typically developing controls underwent MRI with diffusion tensor imaging indices analysis followed by single and paired-pulse transcranial magnetic stimulation with conditioning pulse over the right pre-supplementary motor area followed by left motor cortex test pulse. Neurophysiologic and imaging data relationships to measures of tic severity and suppressibility were also evaluated in tic patients. Pre-supplementary motor area-mediated inhibition of left motor cortex was present in healthy control children but not in chronic tic disorder participants. Less inhibition correlated with worse tic suppressibility (ρ = − 0.73, p = 0.047). Imaging analysis showed increased fractional anisotropy in the right superior longitudinal fasciculus, corpus callosum, corona radiata and posterior limb of the internal capsule (p < 0.05) in tic participants, which correlated with lower self-reported tic suppressibility (ρ = − 0.70, p = 0.05). Physiologic data revealed impaired frontal-mediated motor cortex inhibition in chronic tic participants, and imaging analysis showed abnormalities in motor pathways. Collectively, the neurophysiologic and neuroanatomic data correlate with tic suppressibility, supporting the relevancy to tic pathophysiology. [ABSTRACT FROM AUTHOR]

Tic disorders are neurodevelopmental disorders characterised by the presence of motor or phonic tics, or both. Patients with tic disorders commonly report premonitory urges of tics. Alexithymia is a psychological trait characterised by a difficulty in identifying and expressing one's own feelings and by an externally oriented thinking. We aimed to explore alexithymia in children with tic disorders and in their mothers. Global alexithymia scores of both children with tic disorders and of their mothers did not differ from those of the participants from the control group. In the tic disorder group, however, both children and their mothers showed a cognitive style characterised by operational thinking and a lack of imaginative abilities. The mothers of children with tic disorder reported significantly higher parental stress. Alexithymia was not predictive of tic severity but was predictive of the severity of the premonitory urges. The implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Tourette syndrome is a complex neurobehavioral disorder defined by multiple motor and at least 1 vocal tic, persisting over 1 year, waxing and waning in severity, and not explained by another condition. The condition may range from mild nuisance to debilitating and disabling in severity. Management includes counseling and reassurance, behavioral interventions, pharmacologic, and rarely, surgical interventions. Traditionally, alpha-2 agonists and dopamine receptor antagonists have been utilized. In addition, a number of different pharmacotherapies have been implemented in the search for improved management of tics with better tolerability. In rare, severely disabling cases, neuromodulation with deep brain stimulation may be indicated. Optimal brain targets and candidate selection are still in evolution. This article will review the evidence for current medical and surgical therapies with a focus on recent updates. [ABSTRACT FROM AUTHOR]

Tourette syndrome (TS) is an etiologically heterogeneous disorder, the pathogenesis of which is incompletely understood. Poly(ADP-ribose) polymerase 1 ( PARP1) is involved in regulation of developmental processes and cellular differentiation, in transcription regulation, in DNA repair, and in cell death. However, the relationship between TS and single nucleotide polymorphisms (SNPs) of PARP1 is unknown. Therefore, the aim of this experiment was to test the hypothesis that whether the PARP1 SNP, rs1805404 (c.243C>T, Asp81Asp), had an association with TS. A case–control experiment was designed to test this hypothesis. 123 TS children and 122 normal children were enrolled in this study. Polymerase chain reaction restriction fragment length polymorphism was used for the detection of the PARP1 SNP, rs1805404, in TS patients and normal children. The data showed that there is a significant difference in genotype distributions between these two groups. The CT genotype was a risk factor for TS with an odds ratio of 2.34 for the CT versus TT genotype (95 % CI 1.16–4.74). The data also showed this SNP had an association with TS under recessive model ( P = 0.0426), and TT genotype had a protective effect against TS with an odds ratio of 0.50 (95 % CI 0.26–0.98). The findings of this study suggested that variants in the PARP1 gene might play a role in susceptibility to TS. [ABSTRACT FROM AUTHOR]

Diagnostic categories of tic disorders include both transient and chronic tic disorders and Tourette's disorder. Changes for this group of disorders proposed for the forthcoming DSM-5 system include: (1) The term 'stereotyped' will be eliminated in the definition of tics and the new definition will be applied consistently across all entities of tic disorders; (2) the diagnosis 'Transient Tic Disorder' will change its name to 'Provisional Tic Disorder'; (3) introduction of two new categories in individuals whose tics are triggered by illicit drugs or by a medical condition; (4) specification of chronic tic disorders into those with motor tics or with vocal tics only; (5) specification of the absence of a period longer than 3 months without tics will disappear for Tourette's Disorder. This overview discusses a number of implications resulting from these diagnostic modifications of the diagnostic classifications for use in the clinics. European guidelines for 'Tourette's syndrome and other Tic disorders' were published in 2011 in the ECAP by the 'European Society for the Study of Tourette Syndrome'. The guidelines emphasize the complexity of these neuropsychiatric disorders that require interdisciplinary cooperation between medical professionals, but also patients, parents and teachers for planning of treatment. The main conclusion derived from the guideline for pharmacological treatment is the urgent need for rigorous studies that address the effectiveness of anti-tic medications. The guidelines also emphasize the importance of facilitating the dissemination of several behavioral treatment approaches, such as 'Exposure Response Prevention', yet the most well documented being 'Habit Reversal Training'. [ABSTRACT FROM AUTHOR]

Chronic tic disorders (CTD) are characterized by motor and/or vocal tics. Existing data on the impact of tics in adulthood is limited by small, treatment-seeking samples or by data aggregated across adults and children. The current study explored the functional impact of tics in adults using a nationwide sample of 672 participants with a self-reported CTD. The impact of tics on physical, social, occupational/academic, and psychological functioning was assessed. Results suggested mild to moderate functional impairment and positive correlations between impairment and tic severity. Notable portions of the sample reported 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 lower quality of life. The current study suggests that CTDs can adversely impact functioning in adults and highlights the need for clinical interventions and systemic efforts to address tic-related impairments. [ABSTRACT FROM AUTHOR]

Ten years ago deep brain stimulation (DBS) has been introduced as an alternative and promising treatment option for patients suffering from severe Tourette syndrome (TS). It seemed timely to develop a European guideline on DBS by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). For a narrative review a systematic literature search was conducted and expert opinions of the guidelines group contributed also to the suggestions. Of 63 patients reported so far in the literature 59 had a beneficial outcome following DBS with moderate to marked tic improvement. However, randomized controlled studies including a larger number of patients are still lacking. Although persistent serious adverse effects (AEs) have hardly been reported, surgery-related (e.g., bleeding, infection) as well as stimulation-related AEs (e.g., sedation, anxiety, altered mood, changes in sexual function) may occur. At present time, DBS in TS is still in its infancy. Due to both different legality and practical facilities in different European countries these guidelines, therefore, have to be understood as recommendations of experts. However, among the ESSTS working group on DBS in TS there is general agreement that, at present time, DBS should only be used in adult, treatment resistant, and severely affected patients. It is highly recommended to perform DBS in the context of controlled trials. [ABSTRACT FROM AUTHOR]

This clinical guideline provides recommendations for the behavioural and psychosocial interventions (BPI) of children and adolescents with tic disorders prepared by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). A systematic literature search was conducted to obtain an update on the efficacy of BPI for tics. Relevant studies were identified using computerised searches of the Medline and PsycINFO databases and the Cochrane Library for the years 1950-2010. The search identified no meta-analyses, yet twelve (systematic) reviews and eight randomised controlled trials provided evidence for the current review. Most evidence was found for habit reversal training (HRT) and the available but smaller evidence also supports the efficacy of exposure with response prevention (ERP). Both interventions are considered first line behavioural treatments for tics for both children and adults and should be offered to a patient, taking into account his preference. Treatments that are considered second line or add-on behavioural treatments are contingency management, function based interventions and relaxation training. Neurofeedback is still experimental. Almost no research was identified that examined the efficacy of psychosocial interventions, e.g., psychoeducation and group work. Based on clinical practice, this guideline recommends behavioural treatment as first line offer to patients in most cases. It should be embedded within a psychoeducational and supportive context and can be combined with drug treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tourette's syndrome is a chronic neurobehavioral disorder that can demonstrate refractoriness to conservative treatments, or to invasive nonsurgical treatments such as botulinum toxin infiltration, or to psychobehavioral treatments. In these cases, the surgical option is often proposed, either with lesional interventions, or more recently with deep brain stimulation (DBS). This latter modality is currently preferred because of its reversibility and modularity. Some relevant issues, however, still persist in terms of appropriate indication to treatment, selection of target, and follow-up evaluation. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation (DBS) is a commonly performed surgical technique for the treatment of movement disorders, and recent surgical trials concerning the treatment of a wider range of disorders have recently been published. Despite DBS being non-ablative and minimally invasive, numerous complications and side effects have been recorded. In particular, concerning the growing interest in novel indications for DBS, an enthusiastic approach has put neurosurgeons at risk of underestimating some of the complications that might be associated with specific characters of the treated disease. Objective: Our objective was to evaluate hardware failures and rates of infective complications in correlation to the different indications to DBS, in order to ascertain whether DBS in Tourette syndrome (TS) is characterized by specific risks and pitfalls. Methods: We retrospectively reviewed our experience of 531 procedures on 272 patients treated for various movement disorders, among which 39 patients were treated for conservative treatmentrefractory TS. Results: A statistically significant association of infective complications was found with the TS subgroup. Conclusions: It is our belief that specific behavioral characters of the TS patients may be put into association with this specific complication and need to be considered carefully when indicating DBS as treatment of choice for these patients. [ABSTRACT FROM AUTHOR]

Tourette's syndrome (TS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics as well as psychiatric comorbidities. Recently, differences in maturation of cortical networks using functional connectivity metrics have been described for this disorder. However, adult data on subcortical networks are scarce. In particular, the connectivity of the amygdala, for which a role in the pathophysiology of TS has been established, has not been examined so far. We studied 15 adult TS patients (11 male, aged 30.4 ± 9.7y) and 15 age- and sex-matched controls (11 male, aged 32.0 ± 9.3y) in a functional magnetic resonance imaging study at 1.5T using a simple motor task. We corrected for possible confounds introduced by tics, motion and brain-structural differences as well as age, sex, and medication. Task performance was monitored by simultaneous MR-compatible video-recording. Data were analyzed using an independent component approach sensitive to functional connectivity patterns. A stable component comprising both amygdalae could be identified across all subjects. Additionally, we observed a highly significant increase in coupling between/within amygdalae in the TS group when compared to controls, although behavioral data obtained during scanning did not show significant differences. These findings are expected to add to our understanding of the functional architecture of Tourette's syndrome. [ABSTRACT FROM AUTHOR]

We evaluated the health economic burden of patients with Gilles de la Tourette’s syndrome (GTS) in Germany over a 3-month observation period. Direct and indirect costs were evaluated in 200 outpatients with GTS (mean age 35 ± 11.5 years) in Germany. Patients were recruited from three outpatient departments that specialized in GTS and completed a semi-structured and self-rating interview with questionnaires screening for direct and indirect medical and non-medical costs, health status, depression, amount and severity of symptoms. Costs were obtained from various German medical economic resources. Indirect costs for lost productivity were calculated using the human capital approach. Costs were calculated from the point of view of healthcare and transfer payment providers and the individual patient. Multivariate regression analyses were performed to identify independent cost predictors. Costs are in year 2006–2007 values. Direct costs were 620 ± 1,697.1€, including rehabilitation 98.8 ± 993.6€, hospitalization 195.8 ± 1,267.8€, outpatient treatment 14.0 ± 40.6€, ancillary treatment 51.9 ± 137.4€. Drug costs were 223.1 ± 430.4. The indirect medical costs amounted to 2,511.3 ± 3,809.5€ for productivity loss and to 220.0 ± 1,092€ for absenteeism. The following variables were found to impact on direct costs: employment status, occupational advancement, depression, quality of life, age. Disease severity had no influence on cost. Because of the earlier age of disease onset, indirect costs are higher than direct costs. Interestingly, disease severity did not influence the resource need in this population. Unfortunately, no cost of illness studies are available for comparison. Further health economic studies, especially cost-effectiveness studies, are necessary for a basis for rational resource allocation. [ABSTRACT FROM AUTHOR]

Recent advances in our understanding of the phenomenology, etiology, pathophysiology, and treatment of Tourette syndrome are discussed. Tourette syndrome appears to involve dysfunction of limbic and somatosensory “traffic” through the basal ganglia, within corticostriatal-thalamocortical circuits. Dynamic alterations in the balance of these inputs may dictate the manifestations (sensory, motor, affective, and behavioral) of the disorder at any given time. Individualized assessment and treatment are the keys to optimal treatment of this condition. [ABSTRACT FROM AUTHOR]

Invasive treatment for Gilles de la Tourette syndrome has shown interesting results in a number of published reports; it seems to be evolving into a promising therapeutic procedure for those patients demonstrating disabling clinical pictures who are refractory to conservative treatments. There are important issues concerning the stimulated brain target, with different nuclei currently under investigation. Our group asked in this pilot study whether Tourette syndrome could be treated by tailoring specific brain targets for specific symptoms. Deep brain stimulation for Tourette syndrome may thus in the future be tailored and patient specific, utilizing specific target regions for individual clinical manifestations. In our early experience we did not adequately address non-motor clinical symptoms as we only used a thalamic target. More recently in an obsessive compulsive disease cohort we have had success in using the anterior limb of the internal capsule and nucleus accumbens region as targets for stimulation. We therefore explored the option of a “rescue” procedure for our Tourette patients with persistent obsessive-compulsive disorder following ventralis oralis/centromedianus-parafascicularis (Vo/CM-Pf) deep brain stimulation. Following two cases where rescue anterior limb of internal capsule/nucleus accumbens leads were employed, we performed two additional procedures (anterior limb of the internal capsule plus ventralis oralis/centromedianus-parafascicularis and anterior limb of the internal capsule alone) with some mild improvement of comorbid obsessive–compulsive disorder, although the number of observations in this case series was low. Overall, the effects observed with using the anterior limb of the internal capsule either alone or as a rescue were less than expected. In this report we detail our experience with this approach. [ABSTRACT FROM AUTHOR]

In Tourette syndrome (TS) as a neurodevelopmental disorder not only the tics but also the comorbid conditions change with increasing age. ADHD is highly comorbid with TS and usually impairs psychosocial functioning more than the tics. Its impact on further comorbidity during development is important for clinical practice and still a matter of debate. Aspects of developmental psychopathology considering the impact of ADHD were examined by logistic regression (year wisely) in a cross-sectional sample of children and adolescents ( n = 5060) from the TIC database. In TS+ADHD (compared to TS−ADHD) higher rates of comorbid conditions like OCD, anxiety disorders, CD/ODD and mood disorders were found in children (5–10 years). In adolescents (11–17 years) higher comorbidity rates in TS+ADHD remained only for CD/ODD and mood disorders. Accordingly, for OCD and anxiety disorders there was a steeper year wise increase of these comorbidities in TS−ADHD while it was a similar for CD/ODD and mood disorders in TS−ADHD as well as TS+ADHD. Children with TS+ADHD have more comorbidities than the TS−ADHD group, whereas in both adolescent groups this did no longer hold for OCD and anxiety disorders. These findings indicate that in TS comorbid ADHD is associated with high rates of externalizing and internalizing problems, whereas TS without ADHD is associated only with internalizing problems in adolescence. [ABSTRACT FROM AUTHOR]

Tourette syndrome (TS) is a genetically complex disorder for which no causative genes have been unequivocally identified. Nevertheless, a number of molecular genetic studies have investigated several candidate genes, particularly those implicated in dopamine modulation. The results of these studies were inconclusive, which may be due, at least in part, to the variable ethnicity of the patients included in different studies and the chosen research design. In this study, we used a family-based association approach to investigate the implication of dopamine-related candidate genes, which had been previously reported as possibly associated with TS [genes that encode for the dopamine receptors DRD2, DRD3 and DRD4, the dopamine transporter 1 (SLC6A3) and the monoamine oxidase-A (MAO-A). The studied group was composed of 110 TS patients. These patients were selected from the French Canadian population, which displays a founder effect. Excess transmission of the 7-repeat allele of the DRD4 exon-3 VNTR polymorphism (?2 TDT =4.93, 1 df, P=0.026) and the putative ‘high-activity’ alleles of the MAO-A promoter VNTR polymorphism (?2 TDT =7.124, 1 df P=0.0076) were observed. These results were confirmed in a subgroup of patients with no attention deficit/hyperactivity or obsessive compulsive comorbid disorders. Haplotype analysis using one or two supplemental polymorphism in each of these genes confirmed these associations and allowed one to identify risk haplotypes. No associations were found for DRD2, DRD3 or SLC6A3. These data support the notion that DRD4 and MOA-A genes may confer an increased risk for developing TS in the French Canadian population.Molecular Psychiatry (2004) 9, 272-277. doi:10.1038/sj.mp.4001411 [ABSTRACT FROM AUTHOR]

The objective was to report the possibility that in Tourette’s disorder (TD) the same pathways may not be involved in all patients. Tics in three children affected with TD showed no improvement after treatment with several neuroleptic drugs (D2 blockers) at appropriate doses. However, they did improve greatly and persistently with pergolide treatment. One of the 3 patients showed a less usual tic feature, the most relevant of which resembled violent myoclonias of both upper limbs. This suggests that in these patients the improvement due to pergolide is not linked to an effect on D2-receptors-carrying GABAergic neurons, as usually assumed, because the patients did not respond to neuroleptics acting in this way. In these 3 cases, unlike in other TD patents, a prevalent action of pergolide by pre-synaptic inhibition of dopamine release on D1-receptors-carrying GABAergic neurons is suggested. Therefore, direct and indirect pathways could be differentially involved in different cases of TD. [ABSTRACT FROM AUTHOR]

Purpose Of Review: This article was written in order to bring the reader up to date with developments that have occurred in the treatment of Tourette disorder (TD) over the last 5 years.Recent Findings: Despite the fact that TD has been recognized for over a century, the understanding of the underlying mechanisms remains poor. There has been limited development in the last 5 years for new therapeutic options. Aripipazole is the only newly approved pharmaceutical therapy for TD in the last 5 years, although several medications are under active study. For the most severely affected individuals, there is increasing experience with surgical interventions. One of the most promising areas of research is the work of genetic consortiums currently looking into identifying the underlying pathogenetic basis which in turn will hopefully lead to the development of safer and more effective therapies. [ABSTRACT FROM AUTHOR]