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Long-term Follow-up of a Case of Gilles de la Tourette's syndrome.

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Indian J Psychol Med. 2016 May-Jun;38(3):263-5. doi: 10.4103/0253-7176.183084.

Long-term Follow-up of a Case of Gilles de la Tourette's syndrome.

Abstract

Gilles de la Tourette's syndrome is a combined vocal and multiple motor tic disorder. Here, we present a case of Tourette's syndrome who attended our psychiatric causality with severe depression and suicidal ideation. On reviewing follow-up records of 23 years, we come to know about the academic decline and nicotine dependence in the early childhood. He also developed co-morbid obsessive compulsive disorder (OCD) along with severe depression. He was agitated and self-injurious. We diagnosed him as Gilles de la Tourette's syndrome with co-morbid OCD, depression, nicotine dependence. The patient was treated with haloperidol, sertraline, and clonidine when he developed mixed switch that necessitated us to stop sertraline. Hence, he was treated with a mood stabilizer and he remitted. Here, we want to show how Tourette's syndrome can take a longer course with different co-morbidities in a single person's life. As per our knowledge, such presentation is relatively rare in Indian literature.

Indian Journal of Psychological Medicine, on line publication 2016 May-Jun; doi: 10.4103/0253-7176.183084

PMID: 27335527
 Free PMC Article
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Tics and Tourette's: update on pathophysiology and tic control.

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Curr Opin Neurol. 2016 Jun 14. [Epub ahead of print]

Tics and Tourette's: update on pathophysiology and tic control.

Abstract

PURPOSE OF REVIEW:
To describe recent advances in the pathophysiology of tics and Tourette syndrome, and novel insights on tic control.
RECENT FINDINGS:
The cortico-basal ganglia-thalamo-cortical loops are implicated in generation of tics. Disruption of GABAergic inhibition lies at the core of tic pathophysiology, but novel animal models also implicate cholinergic and histaminergic neurotransmission. Tourette syndrome patients have altered awareness of volition and enhanced formation of habits. Premonitory urges are not the driving force behind all tics. The intensity of premonitory urges depends on patients' capacity to perceive interoceptive signals. The insular cortex is a key structure in this process. The trait intensity of premonitory urges is not a prerequisite of voluntary tic inhibition, a distinct form of motor control. Voluntary tic inhibition is most efficient in the body parts that tic the least. The prefrontal cortex is associated with the capacity to inhibit tics. The management of tics includes behavioral, pharmacological and surgical interventions. Treatment recommendations differ based on patients' age.
SUMMARY: The study of Tourette syndrome pathophysiology involves different neural disciplines and provides novel, exciting insights of brain function in health and disease. These in turn provide the basis for innovative treatment approaches of tics and their associations.

 

Indian Journal of Psychological Medicine, on line publication 2016 May-Jun; doi: 10.4103/0253-7176.183084

PMID: 27310537
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Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome.

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Parkinsonism Relat Disord. 2016 Jun 7. pii: S1353-8020(16)30195-X. doi: 10.1016/j.parkreldis.2016.05.033. [Epub ahead of print]

Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome.

Abstract

INTRODUCTION: Personalized, scheduled deep brain stimulation in Tourette syndrome (TS) may permit clinically meaningful tic reduction while reducing side effects and increasing battery life. Here, we evaluate scheduled DBS applied to TS at two-year follow-up.
METHODS: Five patients underwent bilateral centromedian thalamic (CM) region DBS. A cranially contained constant-current device delivering stimulation on a scheduled duty cycle, as opposed to the standard continuous DBS paradigm was utilized. Baseline vs. 24-month outcomes were collected and analyzed, and a responder analysis was performed. A 40% improvement in the Modified Rush Tic Rating Scale (MRTRS) total score or Yale Global Tic Severity Scale (YGTSS) total score defined a full responder.
RESULTS: Three of the 4 patients followed to 24 months reached full responder criteria and had a mean stimulation time of 1.85 h per day. One patient lost to follow-up evaluated at the last time point (month 18) was a non-responder. Patients exhibited improvements in MRTRS score beyond the improvements previously reported for the 6 month endpoint; on average, MRTRS total score was 15.6% better at 24 months than at 6 months and YGTSS total score was 14.8% better. Combining the patients into a single cohort revealed significant improvements in the MRTRS total score (-7.6 [5.64]; p = 0.02).
CONCLUSION: Electrical stimulation of the centromedian thalamic region in a scheduled paradigm was effective in suppressing tics, particularly phonic tics. Full responders were able to achieve the positive DBS effect with a mean of 2.3 ± 0.9 (SEM) hours of DBS per day.

 

Parkinson & Related Disorders, on line publication 2016 June 7; doi:http://dx.doi.org/10.1016/j.parkreldis.2016.05.033 

PMID:27297737
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Subjective versus objective measures of tic severity in Tourette syndrome - The influence of environment.

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Psychiatry Res. 2016 Jun 3;242:204-209. doi: 10.1016/j.psychres.2016.05.047. [Epub ahead of print]

Subjective versus objective measures of tic severity in Tourette syndrome - The influence of environment.

Abstract

The objective of this study was to examine the influence of environmental challenges on tic expression by subjective and objective measures. The study group consisted of 41 children aged 6-18 years (M=10.15, SD=2.73) with a primary diagnosis of Tourette syndrome. Subjective measures included the Functional Assessment Interview developed for this study and three standard validated instruments. The objective measure was a video-recording of the patients in five daily-life situations: watching television, doing homework, being alone, receiving attention when ticcing, and talking to a stranger. In addition, the effect of premonitory urges on assessment of tic expression was evaluated. The associations between the subjective and objective measures of tic expression were moderate to low. A significantly higher number of tics were observed in the television situation, and a significantly lower number in the alone situation, compared to the other situations. Higher levels of premonitory urge were associated with greater awareness of objectively measured tic expression. In conclusion, tic expression is significantly influenced by the environment. Subjective measures of tic expression may be misleading. These results have implications for refining the clinical assessment of tics, improving research methodology, and developing new therapeutic strategies.

 

Phychiatri Research, on line publication 2016 June 3; doi:

PMID: 27289326

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Social disinhibition is a heritable subphenotype of tics in Tourette syndrome.

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Neurology. 2016 Jul 1. pii: 10.1212/WNL.0000000000002910. [Epub ahead of print]

Social disinhibition is a heritable subphenotype of tics in Tourette syndrome.

Abstract

OBJECTIVE:

To identify heritable symptom-based subtypes of Tourette syndrome (TS).

METHODS:

Forty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined.

RESULTS:

A 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 × 10-18).

CONCLUSIONS:

Expanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies.

© 2016 American Academy of Neurology.

Neurology, on line publication 2016 July 1; doi: 10.1212/WNL.0000000000002910

PMID: 27371487

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Effect of Jian-Pi-Zhi-Dong Decoction on striatal glutamate and γ-aminobutyric acid levels detected using microdialysis in a rat model of Tourette syndrome.

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Neuropsychiatr Dis Treat. 2016 May 19;12:1233-42. doi: 10.2147/NDT.S106330. eCollection 2016.

Effect of Jian-Pi-Zhi-Dong Decoction on striatal glutamate and γ-aminobutyric acid levels detected using microdialysis in a rat model of Tourette syndrome.

Abstract

BACKGROUND:

Jian-Pi-Zhi-Dong Decoction (JPZDD) is a dedicated treatment of Tourette syndrome (TS). The balance of neurotransmitters in the cortico-striato-pallido-thalamo-cortical network is crucial to the occurrence of TS and related to its severity. This study evaluated the effect of JPZDD on glutamate (Glu) and γ-aminobutyric acid (GABA) and their receptors in a TS rat model.

MATERIALS AND METHODS:

Rats were divided into four groups (n=12 each). TS was induced in three of the groups by injecting them with 3,3'-iminodipropionitrile for 7 consecutive days. Two model groups were treated with tiapride (Tia) or JPZDD, while the control and the remaining model group were gavaged with saline. Behavior was assessed by stereotypic score and autonomic activity. Striatal Glu and GABA contents were detected using microdialysis. Expressions of N-methyl-D-aspartate receptor 1 and GABAA receptor (GABAAR) were observed using Western blot and real-time polymerase chain reaction.

RESULTS:

Tia and JPZDD groups had decreased stereotypy compared with model rats; however, the JPZDD group showed a larger decrease in stereotypy than the Tia group at a 4-week time point. In a spontaneous activity test, the total distance of the JPZDD and Tia groups was significantly decreased compared with the model group. The Glu levels of the model group were higher than the control group and decreased with Tia or JPZDD treatment. The GABA level was higher in the model group than the control group. Expressions of GABAAR protein in the model group were higher than in the control group. Treatment with Tia or JPZDD reduced the expression of GABAAR protein. In the case of the mRNA expression, only Tia reduced the expression of N-methyl-D-aspartate receptor 1, compared with the model group.

CONCLUSION:

JPZDD could alleviate impairments in behavior and dysfunctional signaling by downregulating GABAAR in the striatum. We suggest that this acts to maintain the balance of Glu and GABA.

KEYWORDS:

GABAAR; NMDAR1; amino acid neurotransmitter; autonomic activity; cortico-striatal-thalamic-cortical; stereotypy

Neuropsychiatric Disease and Treatment, on line publication 2016 May 19; doi:10.2147/NDT.S106330

PMID: 27279743

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Deep brain stimulation for the treatment of hyperkinetic movement disorders.

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Expert Rev Neurother. 2016 Jun 10:1-12. [Epub ahead of print]

Deep brain stimulation for the treatment of hyperkinetic movement disorders.

Abstract

INTRODUCTION:

Deep brain stimulation effectiveness is well recognized for different movement disorders including Parkinson's disease, dystonia and essential tremor, however several other diseases in this field may benefit from the technique although experience is sparse and evidences of benefit and risks are not established.

AREAS COVERED:

In this review, we explored available evidence for effectiveness and safety of DBS in selected hyperkinetic movement disorders, including tardive dyskinesia, Huntington's disease, neuroacanthocytosis, myoclonus-dystonia, Tourette syndrome, orthostatic and Holmes' tremor. Expert commentary: The data referenced and discussed showed potential effectiveness for DBS in these disabling and refractory diseases. On the other hand, these disorders are quite complex and multifaceted, often composed of different movement disorders, as well as other motor and non-motor symptoms. Therefore, the possible contribution of DBS in improving patients' quality of life should be weighted in a strictly individual basis, keeping in mind the progressive nature of most of these disorders, as well as risk/benefit ratio.

KEYWORDS:

Deep brain stimulation; Huntington’s disease; Tourette syndrome and orthostatic tremor; hyperkinetic movement disorders; myoclonus-dystonia syndrome; neuroacanthocytosis; tardive dyskinesia

Expert review of neurotherapeutics, on line publication 2016 June 10; doi:10.1080/14737175.2016.1196139

PMID: 27254274

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Novel Psychological Formulation and Treatment of "Tic Attacks" in Tourette Syndrome.

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Front Pediatr. 2016 May 11;4:46. doi: 10.3389/fped.2016.00046. eCollection 2016.

Novel Psychological Formulation and Treatment of "Tic Attacks" in Tourette Syndrome.

Abstract

One important, but underreported, phenomenon in Tourette syndrome (TS) is the occurrence of "tic attacks." These episodes have been described at conferences as sudden bouts of tics and/or functional tic-like movements, lasting from 15 min to several hours. They have also been described by patients in online TS communities. To date, there are no reports of tic attacks in the literature. The aim of this article is to stimulate discussion and inform clinical practices by describing the clinical presentation of 12 children (mean age 11 years and 3 months; SD = 2 years and 4 months) with TS and tic attacks, with a detailed case report for one case (13-year-old male). These children commonly present acutely to casualty departments and undergo unnecessary medical investigations. Interestingly, all children reported comorbid anxiety, with worries about the tics themselves and an increased internal focus of attention on tics once the attacks had started. In keeping with other children, the index case reported a strong internal focus of attention, with a relationship between physiological sensations/tic urges, worries about having tic attacks, and behavioral responses (e.g., body scanning, situational avoidance, and other responses). In our experience, the attacks reduce with psychological therapy, for example, the index case attended 13 sessions of therapy that included metacognitive and attention training techniques, as well as cognitive-behavioral strategies. Following treatment, an improvement was seen across a range of measures assessing tics, mood, anxiety, and quality of life. Thus, psychological techniques used to treat anxiety disorders are effective at supporting a reduction in tic attacks through modifying attention, worry processes, and negative beliefs. It is hypothesized that an attentional style of threat monitoring, difficulties tolerating internal sensory urges, cognitive misattributions, and maladaptive coping strategies contribute to the onset and maintenance of tic attacks. These cases provide support for the view that tic attacks are triggered and maintained by psychological factors, thereby challenging the view that tic attacks merely reflect extended bouts of tics. As such, we propose that the movements seen in tic attacks may resemble a combination of tics and functional neurological movements, with tic attacks reflecting episodes of panic and anxiety for individuals with TS.

KEYWORDS:

functional neurological symptoms; non-epileptic seizures; psychogenic seizures; tic disorders; ticcing fits

Frontiers in pediatrics, on line publication 2016 May 11; doi:10.3389/fped.2016.00046

PMID: 27242975

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Tic Frequency Decreases during Short-term Psychosocial Stress - An Experimental Study on Children with Tic Disorders.

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Front Psychiatry. 2016 May 17;7:84. doi: 10.3389/fpsyt.2016.00084. eCollection 2016.

Tic Frequency Decreases during Short-term Psychosocial Stress - An Experimental Study on Children with Tic Disorders.

Abstract

It has been suggested that psychosocial stress influences situational fluctuations of tic frequency. However, evidence from experimental studies is lacking. The current study investigated the effects of the Trier Social Stress Test (TSST-C) on tic frequency in 31 children and adolescents with tic disorders. A relaxation and a concentration situation served as control conditions. Patients were asked either to suppress their tics or to "tic freely." Physiological measures of stress were measured throughout the experiment. The TSST-C elicited a clear stress response with elevated levels of saliva cortisol, increased heart rate, and a larger number of skin conductance responses. During relaxation and concentration, the instruction to suppress tics reduced the number of tics, whereas during stress, the number of tics was low, regardless of the given instruction. Our study suggests that the stress might result in a situational decrease of tic frequency.

KEYWORDS:

Tourette syndrome; Trier Social Stress Test; cortisol; free speech task; heart rate; psychosocial stress; skin conductance; tic disorders

Frontiers in psychiatry on line publication 2016 May 17 doi:10.3389/fpsyt.2016.00084

PMID: 27242554



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Epigenome-Wide Association Study of Tic Disorders.

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2015 Oct 26:1-11. doi: [Epub ahead of print]

Epigenome-Wide Association Study of Tic Disorders..

Abstract

Tic disorders are moderately heritable common psychiatric disorders that can be highly troubling, both in childhood and in adulthood. In this study, we report results obtained in the first epigenome-wide association study (EWAS) of tic disorders. The subjects are participants in surveys at the Netherlands Twin Register (NTR) and the NTR biobank project. Tic disorders were measured with a self-report version of the Yale Global Tic Severity Scale Abbreviated version (YGTSS-ABBR), included in the 8th wave NTR data collection (2008). DNA methylation data consisted of 411,169 autosomal methylation sites assessed by the Illumina Infinium HumanMethylation450 BeadChip Kit (HM450k array). Phenotype and DNA methylation data were available in 1,678 subjects (mean age = 41.5). No probes reached genome-wide significance (p < 1.2 × 10-7). The strongest associated probe was cg15583738, located in an intergenic region on chromosome 8 (p = 1.98 × 10-6). Several of the top ranking probes (p < 1 × 10-4) were in or nearby genes previously associated with neurological disorders (e.g., GABBRI, BLM, and ADAM10), warranting their further investigation in relation to tic disorders. The top significantly enriched gene ontology (GO) terms among higher ranking methylation sites included anatomical structure morphogenesis (GO:0009653, p = 4.6 × 10-15) developmental process (GO:0032502, p = 2.96 × 10-12), and cellular developmental process (GO:0048869, p = 1.96 × 10-12). Overall, these results provide a first insight into the epigenetic mechanisms of tic disorders. This first study assesses the role of DNA methylation in tic disorders, and it lays the foundations for future work aiming to unravel the biological mechanisms underlying the architecture of this disorder.

Twin Research Human Genetics online publication, 26 October 2015; doi:

PMID:
26499864
[PubMed - as supplied by publisher]
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