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Concept: Tourette syndrome

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We assessed the role of prenatal maternal smoking in risk for Tourette syndrome and chronic tic disorder (TS/CT) and pediatric-onset obsessive-compulsive disorder (OCD).

Concepts: Tourette syndrome, Treatment of Tourette syndrome, Tic, Tic disorder, Obsessive–compulsive disorder, Tourettism

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OBJECTIVE Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by multiple motor and phonic tics. While pharmacological and behavioral therapy can be effective in most patients, a subset of patients remains refractory to treatment. Increasing clinical evidence from multiple centers suggests that deep brain stimulation (DBS) of the medial thalamus can be effective in many cases of refractory TS. METHODS The authors retrospectively reviewed outcomes in 13 patients with refractory TS who underwent medial thalamic DBS performed by their team over a 7-year period. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive Compulsive Scale. YGTSS scores were calculated at visits immediately postoperatively and at the most recent follow-up in patients with a minimum of 6 months of postoperative follow-up. Coordinates of the active DBS contacts were calculated and projected onto each patient’s pre- and postoperative images. RESULTS Patients showed an average decrease of 37% (p = 0.0063) in the total tic severity at their first postoperative visit. At their latest visit, their scores achieved significance, decreasing from preoperative scores by an average of 50% (p = 0.0014). The average position of the active contact was noted to be at the junction of the posterior ventralis oralis internus/centromedian-parafascicular nuclei. Device-related complications occurred in 2 patients, necessitating additional surgeries. All patients continued to use the system at last follow-up. CONCLUSIONS The authors' data are consistent with the small but growing body of literature supporting DBS of the ventralis oralis internus/centromedian-parafascicular thalamus as an effective and relatively safe treatment for severe, refractory TS.

Concepts: Deep brain stimulation, Thalamus, Tourette syndrome, Treatment of Tourette syndrome, Tic, Tic disorder

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Tourette syndrome (TS) is characterized by tics, sensorimotor gating deficiencies, and abnormalities of cortico-basal ganglia circuits. A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause. Hdc knockout mice exhibited potentiated tic-like stereotypies, recapitulating core phenomenology of TS; these were mitigated by the dopamine (DA) D2 antagonist haloperidol, a proven pharmacotherapy, and by HA infusion into the brain. Prepulse inhibition was impaired in both mice and humans carrying Hdc mutations. HA infusion reduced striatal DA levels; in Hdc knockout mice, striatal DA was increased and the DA-regulated immediate early gene Fos was upregulated. DA D2/D3 receptor binding was altered both in mice and in humans carrying the Hdc mutation. These data confirm histidine decarboxylase deficiency as a rare cause of TS and identify HA-DA interactions in the basal ganglia as an important locus of pathology.

Concepts: Genetics, Brain, Parkinson's disease, Basal ganglia, Antipsychotic, Dopamine, Tourette syndrome, Haloperidol

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Motor tics are brief, repetitive, involuntary movements that interfere with behavior and appear in multiple neural disorders, most notably, Tourette syndrome. Converging evidence from different lines of research point to the involvement of the corticobasal ganglia system in tics, but the neural mechanism underlying motor tics is largely unknown. An animal model directly linking basal ganglia dysfunction and motor tics indicated that local disinhibition within the basal ganglia input structure, the striatum, induces the appearance of motor tics in both rats and monkeys. Recordings of neuronal activity from multiple brain regions performed in this model during the expression of motor tics showed that tics are associated with phasic changes of neuronal activity throughout the corticobasal ganglia pathway, culminating in the disinhibition of the cortex and the release of a tic. This line of research provides a mechanistic description of the underlying neurophysiology of motor tics and may supply the much needed infrastructure for methodical hypothesis-driven studies of novel clinical treatments.

Concepts: Brain, Cerebral cortex, Cerebrum, Basal ganglia, Tourette syndrome, Tic, Tic disorder, Tourettism

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The comprehensive behavioral intervention for tics (CBIT) represents a safe, effective non-pharmacological treatment for Tourette’s disorder that remains underutilized as a treatment option. Contributing factors include the perceived negative consequences of tic suppression and the lack of a means through which suppression results in symptom improvement. Participants (n = 12) included youth ages 10-17 years with moderate-to-marked tic severity and noticeable premonitory urges who met Tourette’s or chronic tic disorder criteria. Tic frequency and urge rating data were collected during an alternating sequence of tic freely or reinforced tic suppression periods. Even without specific instructions regarding how to suppress tics, youth experienced a significant, robust (72%), stable reduction in tic frequency under extended periods (40 min) of contingently reinforced tic suppression in contrast to periods of time when tics were ignored. Following periods of prolonged suppression, tic frequency returned to pre-suppression levels. Urge ratings did not show the expected increase during the initial periods of tic suppression, nor a subsequent decline in urge ratings during prolonged, effective tic suppression. Results suggest that environments conducive to tic suppression result in reduced tic frequency without adverse consequences. Additionally, premonitory urges, underrepresented in the literature, may represent an important enduring etiological consideration in the development and maintenance of tic disorders.

Concepts: Tourette syndrome, Treatment of Tourette syndrome, Tic, Tic disorder, Tourettism, Coprolalia

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Tourette syndrome (TS) is a disorder characterised by multiple motor and vocal tics and is frequently associated with behavioural problems. Tics are known to be affected by internal factors such as inner tension and external factors such as the surrounding environment. A number of behavioural treatments have been suggested to treat the symptoms of TS, in addition to pharmacotherapy and surgery for the most severe cases. This review compiled all the studies investigating behavioural therapies for TS, briefly describing each technique and assessing the evidence in order to determine which of these appear to be effective. Different behavioural therapies that were used included habit reversal training (HRT), massed negative practice, supportive psychotherapy, exposure with response prevention, self-monitoring, cognitive-behavioural therapy, relaxation therapy, assertiveness training, contingency management, a tension-reduction technique and biofeedback training. Overall, HRT is the best-studied and most widely-used technique and there is sufficient experimental evidence to suggest that it is an effective treatment. Most of the other treatments, however, require further investigation to evaluate their efficacy. Specifically, evidence suggests that exposure with response prevention and self-monitoring are effective, and more research is needed to determine the therapeutic value of the other treatments. As most of the studies investigating behavioural treatments for TS are small-sample or single-case studies, larger randomised controlled trials are advocated.

Concepts: Randomized controlled trial, Therapy, Pharmacotherapy, Classification of Pharmaco-Therapeutic Referrals, Cognitive behavioral therapy, Psychotherapy, Tourette syndrome, Treatment of Tourette syndrome

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Aripiprazole, an atypical antipsychotic drug, has shown potential as a promising candidate for the treatment of Tourette’s disorder (TD). However, the effectiveness and the tolerability profile of aripiprazole in the reduction of tics in children and adolescents with TD have not been systematically analyzed. This meta-analysis aimed to evaluate the effectiveness and tolerability of aripiprazole in children and adolescents with TD.

Concepts: Antipsychotic, Atypical antipsychotic, Tourette syndrome, Tic, Tic disorder, Haloperidol, Risperidone

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Background: Deep brain stimulation for obsessive-compulsive disorder (OCD) has targeted several subcortical nuclei, including the subthalamic nucleus (STN) and the nucleus accumbens. While the most appropriate target is still being looked for, little attention has been given to the side of the stimulated hemisphere in relationship to outcome. Methods: We report 2 patients diagnosed with OCD, one having symmetry obsessions and the other one with sexual-religious obsessive thoughts. They were implanted bilaterally with deep electrodes located at both STN and nuclei accumbens. The effectiveness of the stimulation was tested for every possible paired combination of electrodes guided by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score reduction. Results: In both cases, the combination of electrodes which best relieved the OCD symptoms was both the left STN and left accumbens. In case 1, the preoperative Y-BOCS score was 33, and 1 month after stimulation it was 16. In case 2, the Y-BOCS scores were 33 and 3, respectively, with the patient being free of obsessions. Conclusion: Some reports suggest that lesion stimulation or stimulation of only the right side relieves OCD symptoms. However, anatomical and functional studies are not conclusive as to which side is most affected in OCD. Possibly, each OCD patient has an individualized optimal side to stimulate. © 2013 S. Karger AG, Basel.

Concepts: Deep brain stimulation, Basal ganglia, Tourette syndrome, Obsessive–compulsive disorder

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Background: Deep brain stimulation (DBS) has emerged in recent years as a novel therapy in the treatment of refractory psychiatric disease, including major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and Tourette’s syndrome (TS). Standardized outcome scales were crucial in establishing that DBS was an effective therapy for movement disorders. Objective: In order to better characterize the evidence supporting DBS for various psychiatric diseases, we performed a pooled analysis of those studies which incorporated specific standardized rating scales. Methods: A Medline search was conducted to identify all studies reporting DBS for MDD, OCD, and TS. The search yielded a total of 49 articles, of which 24 were included: 4 related to MDD (n = 48), 10 to OCD (n = 64), and 10 to TS (n = 46). Results: A meta-analysis of DBS for MDD, OCD, and TS in studies employing disease-specific standardized outcome scales showed that the outcome scales all improved in a statistically significant fashion for these psychiatric diseases. Our pooled analysis suggests that DBS for TS has the highest efficacy amongst the psychiatric diseases currently being treated with DBS, followed by OCD and MDD. Conclusion: DBS for psychiatric diseases remains investigational; however, even when studies failing to incorporate standardized outcome scales are excluded, there is statistically significant evidence that DBS can improve symptoms in MDD, OCD, and TS. Standardized disease-specific outcome scales facilitate pooled analysis and should be a required metric in future studies of DBS for psychiatric disease. © 2013 S. Karger AG, Basel.

Concepts: Deep brain stimulation, Mental disorder, Selective serotonin reuptake inhibitor, Abnormal psychology, Major depressive disorder, Tourette syndrome, Body dysmorphic disorder, Obsessive–compulsive disorder