Tourette Syndrome Cases Research Articles

Complex phenotype of Tourette syndrome in a ten-year-old boy (a clinical case)

Aim. The aim of the work is to draw attention to the symptoms associated with Tourette syndrome and to examine the association with comorbid diseases. Materials and methods. A review of the scientific literature on Tourette syndrome (TS) was conducted using the following Keywords “tics”, “Tourette syndrome”, “Tourette obsessive-compulsive disorder, TOCD”, “obsessive-compulsive disorder, OCD”, “attention deficit hyperactivity disorder, ADHD” using PubMed, MEDLINE, EMBASE as search engines. Taking into account studies conducted in the last 10 years, the abstracts of 275 articles were analyzed. Articles were selected for the study based on the criterion of their close relevance to the topic. The study results covered in 49 articles were examined in more detail. A description of a TOCD clinical case was prepared from primary medical documentation with parental informed consent. Results. The prevalence of TS is quite variable, depends on epidemiological research methods and ranges from 0.3 % to 1.0 % worldwide. Given the methodological limitations of most studies, the actual prevalence may be 10 times higher. TS is a progressive disease and is characterized by regular stages. Tourette syndrome-plus is distinguished, including autoaggressive actions besides the basic symptoms of OCD and ADHD. The etiology of TS is still being studied. In particular, the impact of environmental factors is considered: infection or inflammation, perinatal complications and chronic psychosocial stress in childhood. In 70–80 % of cases, TS is a hereditary disorder, making it one of the most heritable childhood-onset neuropsychiatric diseases. Various approaches have been applied to assess the genetic architecture of TS, including candidate gene studies, segregation analysis, linkage analysis, cytogenetics, copy number variants (CNV), rare variation studies, genome-wide association studies (GWAS), and whole exome sequencing (WES). Currently, there is no specific laboratory or genetic test for TS diagnosis. Pharmacological treatments are available but often ineffective; behavioral and surgical treatments are under development. The clinical case of TS in a 10-year-old boy is described with an onset at the age of 7 years following frequent infections, manifested as cephalocaudal motor tics and several vocal tics (coprolalia, echolalia) with a progression to obsessive-compulsive behavior (mysophobia, compulsive skin picking, self-hitting, self-biting, repetitive compulsions). The presented clinical case is of great interest from the viewpoint of somewhat belated diagnosis of TOCD syndrome, as well as indicates the need to continue the search for effective methods of diagnosis and treatment. Conclusions. The case of comorbid OCD and tic disorder is a unique endophenotype combining externalized disinhibited TS movements in parallel with internalized distress reminiscent of OCD. Clinicians should consider these features when choosing treatment methods.

Plum-blossom needle therapy for Tourette syndrome: A case report

IntroductionTourette syndrome (TS) is a neurodevelopmental disorder characterized by the childhood onset of motor and phonic tics, frequently accompanied by behavioral and psychiatric comorbidities. Existing treatments for tics raise safety concerns. In China, acupuncture has been a widely utilized approach for TS, and one specific traditional acupuncture method, plum-blossom needle therapy (PBNT), has exhibited favorable tolerance among pediatric patients. In this report, we present a case of TS treated using PBNT. Case presentationAn 11-year-old boy diagnosed with Tourette syndrome for over five years presented with frequent loud throat clearing, eye blinking, severe abdominal tensing, shoulder shrugging, and upper limb twitching. Plum-blossom needle therapy (PBNT) was administered for 8 weeks, involving two sessions per week. The boy's tic symptoms gradually ameliorated, ultimately becoming minimal following the 8-week treatment period. Specifically, the Yale Global Tic Severity Scale (YGTSS) score decreased from 71 to 20, and the TS Clinical Global Impression Scale of Improvement (CGI-I) score reached 1, signifying 'very much improved' post-treatment. However, the Children and Adolescents' Quality of Life Scale (CAQOL) score exhibited minimal variation, moving from 146 to 150. ConclusionThis case suggests that plum-blossom needle therapy (PBNT) is well-tolerated by children and may be effective in alleviating tics associated with Tourette syndrome (TS). However, further research, particularly large-sample randomized controlled trials, is imperative to establish the efficacy and effectiveness of PBNT.

Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree.

Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder with complex patterns of genetic inheritance. Recent genetic findings in TS have highlighted both numerous common variants with small effects and a few rare variants with moderate or large effects. Here we searched for genetic causes of TS in a large, densely-affected British pedigree using a systematic genomic approach. This pedigree spans six generations and includes 122 members, 85 of whom were individually interviewed, and 53 of whom were diagnosed as ‘cases’ (consisting of 28 with definite or probable TS, 20 with chronic multiple tics [CMT], and 5 with obsessive-compulsive behaviors [OCB]). A total of 66 DNA samples were available (25 TS, 15 CMT, 4 OCB cases and 22 unaffecteds) and all were genotyped using a dense single nucleotide polymorphism (SNP) array to identify shared segments, copy number variants (CNVs), and to calculate genetic risk scores. Eight cases were also whole genome sequenced to test whether any rare variants were shared identical by descent. While we did not identify any notable CNVs, single nucleotide variants, indels or repeat expansions of near-Mendelian effect, the most distinctive feature of this family proved to be an unusually high load of common risk alleles for TS. We found that cases within this family carried a higher load of TS common variant risk similar to that previously found in unrelated TS cases. Thus far, the strongest evidence from genetic data for contribution to TS risk in this family comes from multiple common risk variants rather than one or a few variants of strong effect.

Rapid Onset Functional Tic-Like Behaviors in Young Females During the COVID-19 Pandemic.

Rapid Onset Functional Tic-Like Behaviors in Young Females During the COVID-19 Pandemic.

Gilles De La Tourette Syndrome: A Case and A Brief Review of the Early Documentation of the Syndrome in The Literature

Background: Gilles de la Tourette syndrome is a neuro-psychiatric condition associated with rather bizarre manifestations and generally affects children with normal intelligence. The condition has the potential to make an intelligent child a victim of the disorder, and unfavorably affects his/her school performance and lead to social rejection and isolation. Awareness by the community, educators, and also medical practitioners is useful and help in avoiding the loss of such children who have the potential to be a talented person. The aim of this paper is to present a case and to provide a brief account on the early documentation of syndrome in the literature. Patients and Methods: The case of a ten-year old boy with Gilles de la Tourette syndrome is described and the relevant literatures were reviewed to outline the early documentation of the disorder in the literature. Results: A.Y was first seen at the pediatric psychiatric clinic of the Children Teaching Hospital of Baghdad Medical City at the age of ten years because they were saying at school that the boy is crazy because of his abnormal behaviors. The boy’s abnormal behaviors mentioned by his mother included shrugging his shoulders, shrugging his hips with unusual movements of the legs as if he was dancing, unusual facial grimace and lip licking, rubbing his chin, licking the back of his hand, producing abnormal sounds from his throat, and echolalia. Review of the earliest relevant literature revealed that the condition was first described in a book entitled “Malleus Maleficarum” which means “Witch’s hammer”. Jean Marc Gaspard Itard, a French doctor described the first case of Tourette syndrome in 1825. Conclusion: Awareness of this condition by the community, educators, and also medical practitioners is useful and help in avoiding the loss of such children who have the potential to be a talented person.

Association of Genetic Variation in the 3'UTR of LHX6, IMMP2L, and AADAC With Tourette Syndrome.

Background: Tourette Syndrome (TS) is a neurodevelopmental disorder that presents with motor and vocal tics early in childhood. The aim of this study was to investigate genetic variants in the 3' untranslated region (3'UTR) of TS candidate genes with a putative link to microRNA (miRNA) mediated regulation or gene expression.Methods: We used an in silico approach to identify 32 variants in the 3'UTR of 18 candidate genes putatively changing the binding site for miRNAs. In a sample composed of TS cases and controls (n = 290), as well as TS family trios (n = 148), we performed transmission disequilibrium test (TDT) and meta-analysis.Results: We found positive association of rs3750486 in the LIM homeobox 6 (LHX6) gene (p = 0.021) and rs7795011 in the inner mitochondrial membrane peptidase subunit 2 (IMMP2L) gene (p = 0.029) with TS in our meta-analysis. The TDT showed an over-transmission of the A allele of rs1042201 in the arylacetamide deacetylase (AADAC) gene in TS patients (p = 0.029).Conclusion: This preliminary study provides further support for the involvement of LHX6, IMMP2L, and AADAC genes, as well as epigenetic mechanisms, such as altered miRNA mediated gene expression regulation in the etiology of TS.

Targeting Cognitions, Emotions, and Behaviors in a Complex Case of Tourette Syndrome: Illustration of a Psychophysiological Perspective

Recent research stresses that cognitive and affective processes are implicated in Tourette Syndrome (TS) and might influence treatment. The cognitive-behavioral and psychophysiological (CoPs) approach posits that negative appraisals and maladaptive action-planning elicit negative emotions and behaviors that increase muscular tension and thus the urge to tic in TS. Hence, the CoPs targets cognitive-behavioral and affective processes increasing tension prior to tic onset. This article provides clinically novel information in the implementation and utility of the CoPs approach in a severe case of a young man with TS and a range of comorbidities marked by negative cognitions and emotions as well as planning deficits with a long-term follow-up. He received 14 sessions of CoPs therapy. Tic severity significantly decreased post-treatment with maintenance up to 36-months. The process measure of action-planning improved significantly from pre-treatment to 12-months follow-up. Results support the feasibility and acceptability of the CoPs in treating complex TS cases.

CM-Pf deep brain stimulation and the long term management of motor and psychiatric symptoms in a case of Tourette syndrome

Tourette syndrome is a rare neuropsychiatric disorder affecting the cortico-striato-thalamo-cortical system. The disease manifests in childhood with tics and various psychiatric comorbidities. Cases of refractory Tourette syndrome are valuable candidates for functional neurosurgery. The thalamic centromedian-parafascicular complex is an experimental target that shows a promising role in Tourette syndrome deep brain stimulation, due to pathophysiologic evidences. We have shown on a long term follow-up, that thalamic deep brain stimulation, targeted on the centromedian-parafascicular complex, could modulate motor (i.e. tics) symptoms and owns a putative effect on various psychiatric aspects. Non-responding psychiatric symptoms could be due to the aberrant developmental environment of young Tourette patients more than disease itself. Centromedian-parafascicular complex is intriguingly embedded in motor, associative and limbic pathways and should be further investigated in his role for neuromodulation of human movement and behavior.

Collaborative Genome-Wide Association and Copy Number Variation Analysis of Tourette Syndrome

Tourette Syndrome (TS) is a childhood-onset developmental disorder that has one of the highest heritabilities among neuropsychiatric diseases with non-Mendelian inheritance. However, no definitive TS susceptibility genes have been identified to date. We have previously demonstrated that TS is highly polygenic, and that 30-50% of TS heritability can be captured by SNP genotyping arrays.Here, we present the most recent results from the current TS genome-wide association study (GWAS) and copy number variant (CNV) analyses. In the current TS GWAS mega-analysis of 4232 European ancestry TS cases and 8318 ancestry matched controls, one locus on chromosome 2p16 surpassed the genome-wide significant threshold (rs2708146, p=5.1x10-8). This SNP lies within a large 1Mb haplotype containing one transcript, LINC01122, an uncharacterized long, intergenic, non-coding RNA (lincRNA), that is expressed primarily in mid-fetal human brain development (15-16 pcw), with strongest expression in developing cerebral cortex. Pairwise correlational analysis of Brainspan project data across pre-natal time points identified the highest co-expression of LINC01122 with BCL11A, a gene 1 Mb centromeric to LINC01122 that has been found previously to harbor recurrent de novo loss-of-function mutations in individuals with autism-spectrum disorder. Subsequent analyses demonstrate that LINC01122 and BCL11A lie within the same topologically-associated domain (TAD) in human fetal cortex, suggesting that both transcripts are co-regulated.In the CNV analysis of 2,434 European ancestry TS cases and 4,093 ancestry matched controls, we identified a significant global burden of rare (<1% frequency) genic CNVs that was most pronounced in large (>1 Mb), singleton CNVs (OR 2.28 [1.39-3.79], p=1.2x10-3) and in CNVs previously classified as pathogenic by the American College of Medical Genetics (OR 3.03 [1.85-5.07], p=1.5x10-5). Two individual CNV loci surpassed genome-wide significance both for point-wise and gene-based tests, as determined empirically by permutations: deletions in NRXN1-alpha (Pseg=7.0x10-6; Pseg-corr=1.0x10-3; OR 20.3[2.6-156.2]) and duplications across CNTN6 (Pseg=5.4x10-5, Pseg-corr=6.9x10-3; OR=10.1 [2.3-45.4]). 1% of TS cases carried one of these two CNVs, with an additional 0.5% harboring an ACMG pathogenic CNV outside these two loci.In conclusion, we present evidence for one GWAS locus and two rare CNVs that exceed the genome-wide significance threshold, representing the first convincing TS susceptibility loci. The members of this symposium are now preparing for large-scale meta-analyses of GWAS and CNV datasets from 5 international TS genetics consortia in 13,000 TS cases and 37,000 controls.

Genetic Studies of Tic Disorders and Tourette Syndrome.

Tourette syndrome (TS) is a complex disorder characterized by repetitive, sudden, and involuntary movements or vocalizations, called tics. Tics usually appear in childhood, and their severity varies over time. In addition to frequent tics, people with TS are at risk for associated problems including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and problems with sleep. TS occurs in most populations and ethnic groups worldwide, and it is more common in males than in females. Previous family and twin studies have shown that the majority of cases of TS are inherited. TS was previously thought to have an autosomal dominant pattern of inheritance. However, several decades of research have shown that this is unlikely the case. Instead, TS most likely results from a variety of genetic and environmental factors, not changes in a single gene. In the past decade, there has been a rapid development of innovative genetic technologies and methodologies, as well as significant progress in genetic studies of psychiatric disorders. In this review, we will briefly summarize previous genetic epidemiological studies of TS and related disorders. We will also review previous genetic studies based on genome-wide linkage analyses and candidate gene association studies to comment on problems of previous methodological and strategic issues. Our main purpose for this review will be to summarize the new genetic discoveries of TS based on novel genetic methods and strategies, such as genome-wide association studies (GWASs), whole exome sequencing (WES), and whole genome sequencing (WGS). We will also compare the new genetic discoveries of TS with other major psychiatric disorders in order to understand the current status of TS genetics and its relationship with other psychiatric disorders.

Deep brain stimulation of anteromedial globus pallidus internus for severe Tourette syndrome.

Tourette syndrome (TS) is a complex disorder characterized by tics and is associated with behavioral problems. Although its intensity decreases in adolescence and adult life, in some cases it continues to remain severe and refractory to medical treatment. Deep brain stimulation has been offered as a treatment option in such cases. We report two cases of TS treated with of anteromedial globus pallidum internus. Both the cases had good postoperative control of tics and associated obsessive–compulsive behavior.

Delta-9-tetrahydrocannabinol for the treatment of a child with Tourette syndrome: case report

Background: Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by motor and vocal tics. In severe treatment-resistant cases of TS, cannabis-based medicine could be used alternatively as a therapy of last choice. Case Presentation: We present the case of an 7-year-old boy with severe TS and comorbid attention deficit/hyperactivity disorder (ADHD), who significantly benefitted from treatment with cannabis-based medicine. During an episode with increased tics, he became depressed, developed suicidal ideation, and exhibited separation anxiety resulting in social isolation. As treatment with various antipsychotics and Habit Reversal Training turned out to be unsuccessful, we implemented therapy with oral delta-9-tetrahydrocannabinol (THC) as oil-based drops. Starting dose was as low as 0.7 mg THC/day once a day and was gradually increased up to a maximum dose of 29.4 mg THC/day, resulting in a significant improvement of both tics and behavioral symptoms. Follow-up visits over a period of 4 months demonstrated a sustained treatment effect without any adverse events. Conclusion: From this single case report, it is suggested that THC is effective and safe in the treatment of tics, depression, and ADHD in children with severe and otherwise treatment-resistant TS.

Identification of candidate genes involved in the etiology of sporadic Tourette syndrome by exome sequencing.

Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by chronic motor and vocal tics. Although there is a large genetic contribution, the genetic architecture of TS remains unclear. Exome sequencing has successfully revealed the contribution of de novo mutations in sporadic cases with neuropsychiatric disorders such as autism and schizophrenia. Here, using exome sequencing, we investigated de novo mutations in individuals with sporadic TS to identify novel risk loci and elucidate the genetic background of TS. Exome analysis was conducted for sporadic TS cases: nine trio families and one quartet family with concordant twins were investigated. Missense mutations were evaluated using functional prediction algorithms, and their population frequencies were calculated based on three public databases. Gene expression patterns in the brain were analyzed using the BrainSpan Developmental Transcriptome. Thirty de novo mutations, including four synonymous and four missense mutations, were identified. Among the missense mutations, one in the rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR)-coding gene (rs140964083: G > A, found in one proband) was predicted to be hazardous. In the three public databases analyzed, variants in the same SNP locus were absent, and variants in the same gene were either absent or present at an extremely low frequency (3/5,008), indicating the rarity of hazardous RICTOR mutations in the general population. The de novo variant of RICTOR may be implicated in the development of sporadic TS, and RICTOR is a novel candidate factor for TS etiology.

Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome

Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR= 2.28, 95% CI [1.39-3.79], p= 1.2× 10-3) and known, pathogenic CNVs (OR= 3.03 [1.85-5.07], p= 1.5× 10-5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR= 20.3, 95% CI [2.6-156.2]; CNTN6 duplications, OR= 10.1, 95% CI [2.3-45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS.

The International Deep Brain Stimulation Registry and Database for Gilles de la Tourette Syndrome: How Does It Work?

Tourette Syndrome (TS) is a neuropsychiatric disease characterized by a combination of motor and vocal tics. Deep brain stimulation (DBS), already widely utilized for Parkinson's disease and other movement disorders, is an emerging therapy for select and severe cases of TS that are resistant to medication and behavioral therapy. Over the last two decades, DBS has been used experimentally to manage severe TS cases. The results of case reports and small case series have been variable but in general positive. The reported interventions have, however, been variable, and there remain non-standardized selection criteria, various brain targets, differences in hardware, as well as variability in the programming parameters utilized. DBS centers perform only a handful of TS DBS cases each year, making large-scale outcomes difficult to study and to interpret. These limitations, coupled with the variable effect of surgery, and the overall small numbers of TS patients with DBS worldwide, have delayed regulatory agency approval (e.g., FDA and equivalent agencies around the world). The Tourette Association of America, in response to the worldwide need for a more organized and collaborative effort, launched an international TS DBS registry and database. The main goal of the project has been to share data, uncover best practices, improve outcomes, and to provide critical information to regulatory agencies. The international registry and database has improved the communication and collaboration among TS DBS centers worldwide. In this paper we will review some of the key operation details for the international TS DBS database and registry.

Thalamocortical network activity enables chronic tic detection in humans with Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Deep brain stimulation (DBS) is an emerging therapy for severe cases of TS. We studied two patients with TS implanted with bilateral Medtronic Activa PC + S DBS devices, capable of chronic recordings, with depth leads in the thalamic centromedian–parafascicular complex (CM-PF) and subdural strips over the precentral gyrus. Low-frequency (1–10 Hz) CM-PF activity was observed during tics, as well as modulations in beta rhythms over the motor cortex. Tics were divided into three categories: long complex, complex, and simple. Long complex tics, tics involving multiple body regions and lasting longer than 5 s, were concurrent with a highly detectable thalamocortical signature (average recall [sensitivity] 88.6%, average precision 96.3%). Complex tics were detected with an average recall of 63.9% and precision of 36.6% and simple tics an average recall of 39.3% and precision of 37.9%. The detections were determined using data from both patients.

A report on the first case of Tourette syndrome associated with segmental agenesis of corpus callosum

A report on the first case of Tourette syndrome associated with segmental agenesis of corpus callosum

Utility of the diagnostic interview schedule for children for assessing Tourette syndrome in children.

The Diagnostic Interview Schedule for Children IV (DISC) has been used extensively in research and screening. Despite wide use, little information exists on the validity of the DISC for diagnosing tic disorders. Participants were 181 youth with expert clinician-diagnosed Tourette syndrome (TS). Using expert clinician-diagnosed TS as the gold standard, the sensitivity of the DISC-Y (youth, 0.27) and DISC-P (parent, 0.44) was poor. The DISC-Y identified 29.7% of youth with diagnosed TS whereas the DISC-P identified 47.4% of cases. Only 54% of cases of TS were detected by either the DISC-Y or -P. Diagnostic agreement between the DISC and expert clinician diagnosis was poor. The DISC-Y/P results did not differ as a function of tic severity. Despite utility for assessing child psychiatric disorders, the sensitivity of the DISC for detecting TS appears poor. This study suggests that DISC has low agreement with expert clinician diagnosis of TS. Findings highlight the need for modification of the DISC and/or the identification and development of more sensitive measures for TS screening.

Prevalence of anxiety disturbs in patients with Tourette syndrome and tic disturb

Tourette syndrome (TS) is characterized by a wide phenotypic polymorphism and this heterogeneity is due partly to the association with several neuropsychiatry disorders. These comorbidities are showed in the 90% of TS cases. The aim of this transversal study is to analyze the presence and prevalence of different psychopathological conditions that could be expressed with tic disorder (TD) and specifically in TS. We examined a sample of 102 patients, between 7 and 17.6 years old, with a diagnosis DSM-IV-TR of TD, using the self-report SAFA. Different correlations between these comorbidities and clinical variables are also analyzed. Our data underlined most of all a prevalence of anxiety disorders in the 31.4% of our patients with TD, of depression in the 27.44%, and of somatization symptoms in the 22.54%. Anxiety disorders seem to be linked with the variables of patients'age, duration of disease, gender, pharmacological treatment and presence of comorbidity for obsessive-compulsion disorder (OCD). This study suggests the important prevalence of non-OCD anxiety disorders in TD patients and shows they have a central role in their psychopathological profile. However, the basilar question if these disturbs are primary or secondary to the TD is still to be clarify.

CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1

Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.