Contrasting features between Tourette syndrome and secondary tic disorders.

Tics are rapid, recurrent, non-rhythmic movements or emitted sounds. Tics are the hallmark of Tourette syndrome (TS); however, a number of other disorders may be associated with tics, so-called secondary tic disorders (STD). We assessed clinical history and performed blinded evaluations of video-recordings from patients with TS and STD in order to identify features that may differentiate tics associated with TS vs STD. There were 156 patients with TS and 38 with STD, 21 of whom had functional (psychogenic) tics. Patients with TS were more frequently male and had a younger age at onset. Tics in TS tend to involve muscles in the cranial-cervical area more often and have greater severity and complexity than those in patients with STD. Similar findings were observed when contrasting patients with TS with patients with functional tics only. Simple phonic tics showed the greatest diagnostic accuracy for TS, compared with STD, but marked overlap in the types of tics and comorbidities was observed between patients with TS and STD. Patients with TS were more likely males, had a younger age at onset, phonic tics and motor tics affecting predominantly the head and neck area, and had a greater complexity and severity of tics than those with STD. When these features are absent a consideration should be given to the possibility of a tic disorder other than TS.

Increased Number of Functional Tics Seen in Danish Adolescents during the COVID-19 Pandemic.

BACKGROUND: Global increase in functional tics in adolescents has been observed. Differentiating functional from classic tics is important since pathophysiology and treatment differ. We investigated possible triggers for development of functional tics and discuss the possible role of the coronavirus disease 2019 (COVID-19) pandemic and social media exposure in cases of functional tics seen during this period. Moreover, the treatment, and its efficacy is discussed. METHODS: Medical records of 28 Danish adolescents diagnosed with functional tics at the National Tourette Clinic, Department of Pediatrics, Herlev University Hospital, Denmark, from May 2020 to June 2021 have been retrospectively reviewed. Descriptive statistical analyses were used to analyze the data. MAIN FINDINGS: A total of 28 patients diagnosed with functional tics were included, 96.4% girls and 3.6% boys, mean age 14.4 years. Tic phenomenology differed from classic tics with more complex tics and no rostrocaudal progression. Note that 69.2% reported harmful tics. Also, 78.6% had trauma/precipitating event and 40% denounced lockdown related to the COVID-19 pandemic as trigger, both prior to onset of functional tics. Note that 60.7% reported psychiatric symptoms/diagnoses, 42.9% had a first-degree family member with psychiatric symptoms/diagnoses, and 96.4% were exposed to tics on social media prior to onset. Treatment consisted of psychoeducation, elements from cognitive behavioral therapy, and focus on psychiatric symptoms. All patients responded to the treatment. CONCLUSION: The vulnerability of the adolescents is characteristic. Treatment strategy has shown immediate positive effect. Consequences of the COVID-19 pandemic in combination with exposure to tics on social media could be part of the cause for the increase in number of functional tics.

Polygenic and environmental determinants of tics in the Avon Longitudinal Study of Parents and Children.

Tourette syndrome (TS) is caused by multiple genetic and environmental factors. Yet, little is known about the interplay of these factors in the occurrence of tics. We investigated whether polygenic risk score (PRS) of TS and pregnancy-related factors together enhance the explained variance of tic occurrence in the Avon Longitudinal Study of Parents and Children (Ncases  = 612; Ncontrols  = 4,201; 50% male; mean age 13.8 years). We included a cumulative adverse pregnancy risk score, maternal anxiety and depression, and maternal smoking and alcohol use during pregnancy. We investigated possible joint effects of genetic and pregnancy-related risk factors using a multivariable approach, and explored mediation effects between the pregnancy-related risk factors in explaining tic presence. The PRS and the cumulative adverse pregnancy risk score, maternal anxiety, or maternal depression explained significantly more variance of tic presence compared to models including only the PRS. Furthermore, we found that the cumulative adverse pregnancy risk score mediated the association between several pregnancy-related factors (maternal anxiety, depression, and smoking) and tics. The combination of a PRS and pregnancy-related risk factors explained more variance of tics in a general population cohort compared to studying these factors in isolation.

TikTok and tics: the possible role of social media in the exacerbation of tics during the COVID lockdown.

Background and purpose: Over the past year, many cases with newly onset or significantly exacerbated tic disorders were observed worldwide, where some aspects of the clinical presentation or the symptomatology were atypical for established tic diagnoses. Our purpose was to describe the atypical cases and raise relevant diagnostic issues. Methods: Consecutive cases with atypical tic presentations were documented. Results: Five atypical tic cases are described. These cases shared some common characteristics, most notably the fact that all of them had been exposed to online presentation of ticking behaviour on social media platforms prior to the de novo development or exacerbation of their tics. Even though the order of events suggests causality and therefore the diagnosis of a functional tic disorder, unambiguous criteria for classifying atypical tics as functional symptoms are lacking. Differentiating neurodevelopmental and functional tics in childhood is currently problematic. Conclusion: Based on the currently unresolved issues in differential diagnosis, the importance of watchful waiting and behavioural interventions is highlighted to avoid unwarranted pharmacotherapy.

Beyond tics: movement disorders in patients with Tourette syndrome.

BACKGROUND: Tics are the hallmark of Tourette syndrome (TS). However, TS patients may have a particular vulnerability to develop other movement disorders (MDs), such as dystonia, chorea, stereotypy, and other hyperkinetic disorders that may be wrongly attributed to tics. MATERIALS AND METHODS: We studied a cohort of 201 patients with motor and phonic tics associated with TS to determine if they have additional, co-existent, MDs. RESULTS: There were 67 (33.3%) patients with comorbid non-tic MDs. Phenomenology-wise, piano-playing movements resembling chorea or myoclonus, were the most common non-tic movement, observed in 11% of cases, followed by stereotypies (8.0%), tremor, dystonia and parkinsonism, 5.0% each. Drug-induced was the most common etiology (6.0%), followed by functional movement disorders (5.0%) and tardive phenomena (5.0%). No clear etiology was identified in most patients. Piano-playing movements, were associated with a younger age at onset (P = 0.004) and younger age at presentation (P < 0.001). Patients with drug-induced movements and tardive phenomena had a lower frequency of craniofacial tics. FMDs, and idiopathic MDS showed no specific associations with TS. Tic severity was not a predictor of any co-existent MD. CONCLUSION: About a third of patients with TS present with comorbid MDs which should be differentiated and distinguished from tics as their etiopathogenesis and treatment may be different.

Tonic Tics in Gilles de la Tourette Syndrome.

AIM: Tonic tics (TTs) are a part of a clinical picture of Gilles de la Tourette syndrome (GTS) and manifest themselves as sustained and isometric contraction of a muscle group devoid of the movement effect or accompanied by only slight visible motion. The aim of this study was to evaluate the prevalence and phenomenology of TTs, and to assess the clinical associations of TTs with tic severity and comorbidities in patients with GTS. METHODS: We performed a one-time registration study in a cohort of 241 consecutive outpatients with GTS aged 5 to 50 years (188 males, 153 patients under the age of 18 years). All patients were personally interviewed and examined. RESULTS: TTs occurred in 85.2% of adults and 63.9% of children and adolescents. Most frequently reported types of TTs were tensing of the abdomen (58.7%), neck (52.7%), and upper limbs (50.3%). Multivariate statistical analysis showed a significant correlation between TTs and the total number of simple tics, total number of complex tics, and age at evaluation. In the group of children and adolescents, an additional significant variable was the duration of GTS. In the group of adults, significant parameters were total number of simple tics, total number of complex tics, peak tic severity ever experienced, premonitory urges, and the presence of dystonic tics. CONCLUSION: TTs belong to the tic spectrum, common and early symptoms of GTS, are associated with overall a greater number of tics which are more severe, and with more comorbidities.

Effects of comorbidity on Tourette's tic severity and quality of life.

OBJECTIVE: The aim of this study is to gain more insight in the differential contributions of anxiety, depression and obsessive-compulsive (OC) symptom severity to quality of life (QoL) and tic severity in adults with Tourette Disorder (TD). METHODS: Self-reported OC symptom, anxiety and depression severity measures were used to investigate their predictive value on QoL and Tic severity in adult TD patients (N = 187), using correlation, regression, and mediation analyses. RESULTS: Tic severity has no effect on QoL. Depression severity directly reduces QoL, whereas anxiety and OC symptom severity have an indirect effect on QoL, mediated by depression severity. OC symptom severity directly affects tic severity, whereas depression and anxiety severity do not have a direct effect on tic or OC severity. Finally, anxiety severity indirectly impacts tic severity, with OC symptom severity functioning as a mediator. CONCLUSION: In line with and extending previous studies, these findings indicate that OC symptom severity directly influences tic symptom severity whereas depression severity directly influences QoL in TD. Results imply that to improve QoL in TD patients, treatment should primarily focus on diminishing OC and depressive symptom severity rather than focusing on tic reduction.

Gilles de la Tourette syndrome as a paradigmatic neuropsychiatric disorder.

Gilles de la Tourette syndrome is a chronic and complex tic disorder accompanied by specific behavioral problems in the majority of patients. With its multifaceted interplay between motion and emotion, this condition is a paradigmatic example of the science and art of clinical neuropsychiatry. This review article encompasses the clinical phenomenology of motor and vocal tics and associated sensory experiences (premonitory urges), as well as the behavioral spectrum of the most common comorbidities, including obsessive-compulsive disorder, attention-deficit and hyperactivity disorder, affective symptoms, and impulsivity. Knowledge of the contributions of both tics and behavioral problems to patients' health-related quality of life across the lifespan should assist treating clinicians in formulating a targeted management plan. Although the exact pathophysiology of Gilles de la Tourette syndrome remains elusive, research into therapeutic interventions has expanded the range of available interventions across multiple domains. A thorough understanding of the neurology and psychiatry of this condition is of key importance to meet the needs of this patient population, from the formulation of an accurate diagnosis to the implementation of effective treatment strategies.

Botulinum toxin for motor and phonic tics in Tourette's syndrome.

BACKGROUND: Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before the age of 18 years, in the absence of secondary causes. Treatment of motor and phonic tics is difficult and challenging. OBJECTIVES: To determine the safety and effectiveness of botulinum toxin in treating motor and phonic tics in people with Tourette's syndrome, and to analyse the effect of botulinum toxin on premonitory urge and sensory tics. SEARCH METHODS: We searched the Cochrane Movement Disorders Group Trials Register, CENTRAL, MEDLINE, and two trials registers to 25 October 2017. We reviewed reference lists of relevant articles for additional trials. SELECTION CRITERIA: We considered all randomised, controlled, double-blind studies comparing botulinum toxin to placebo or other medications for the treatment of motor and phonic tics in Tourette's syndrome for this review. We sought both parallel group and cross-over studies of children or adults, at any dose, and for any duration. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods to select studies, assess risk of bias, extract and analyse data. All authors independently abstracted data onto standardized forms; disagreements were resolved by mutual discussion. MAIN RESULTS: Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette's syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was very low. Nine people had muscle weakness following the injection, which could have led to unblinding of treatment group assignment. No data were available to evaluate whether botulinum injections led to immunoresistance to botulinum. AUTHORS' CONCLUSIONS: We are uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette's syndrome.

Tics and Tourette: a clinical, pathophysiological and etiological review.

PURPOSE OF REVIEW: Describe developments in the etiological understanding of Tourette syndrome. RECENT FINDINGS: Tourette syndrome is a complex heterogenous clinical syndrome, which is not a unitary entity. Pathophysiological models describe gamma-aminobutyric acid-ergic-associated disinhibition of cortico-basal ganglia motor, sensory and limbic loops. MRI studies support basal ganglia volume loss, with additional white matter and cerebellar changes. Tourette syndrome cause likely involves multiple vulnerability genes and environmental factors. Only recently have some vulnerability gene findings been replicated, including histidine decarboxylase and neurexin 1, yet these rare variants only explain a small proportion of patients. Planned large genetic studies will improve genetic understanding. The role of inflammation as a contributor to disease expression is now supported by large epidemiological studies showing an association with maternal autoimmunity and childhood infection. Investigation of blood cytokines, blood mRNA and brain mRNA expression support the role of a persistent immune activation, and there are similarities with the immune literature of autistic spectrum disorder. Current treatment is symptomatic, although there is a better appreciation of factors that influence treatment response. SUMMARY: At present, therapeutics is focused on symptom-based treatments, yet with improved etiological understanding, we will move toward disease-modifying therapies in the future.

Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. CASE PRESENTATION: A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. CONCLUSION: The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

Relationship of serum ferritin level and tic severity in children with Tourette syndrome.

PURPOSE: Tics can be considered hyperkinetic movements akin to restless leg syndrome (RLS). Drawing the analogy of iron deficiency as an etiology of RLS, it is conceivable that iron deficiency may underlie or worsen tics in Tourette syndrome (TS). The purpose of this study was to evaluate the relationship between serum ferritin levels and tic severity, as well as consequent impact on life, in children with TS. METHODS: Children <18 years, diagnosed with TS during 2009-2015, were reviewed. Only those with serum ferritin testing were included. The following data were collected: tic severity, impact on life, medication, comorbidities, blood count, and serum ferritin at diagnosis and follow-up. RESULTS: In fifty-seven patients, M:F = 2:1, serum ferritin was 48.0 ± 33.28 ng/mL, tic severity score 2.3 ± 0.80, impact on life score 2.2 ± 0.93, and composite score 4.57 ± 1.6. Serum ferritin was not influenced by comorbid obsessive compulsive disorder (OCD), attention deficit hyperactive disorder (ADHD), or anxiety (P > 0.16). Thirty-eight percent with low serum ferritin (≤50 ng/mL) (n = 37) had severe tics (>5 composite score), compared with 25% in normal ferritin group (n = 20). Over 6-12 months, tic severity score improved in both iron treated groups, deficient (2.70 to 1.90) and sufficient (2.40 to 1.95), whereas tics worsened or remained the same when not treated with iron. CONCLUSIONS: Our data suggest iron deficiency may be associated with more severe tics with higher impact on TS children, independent of the presence of OCD, ADHD, or anxiety. Iron supplementation showed a trend towards improvement of tic severity upon follow-up. We suggest a double-blind, placebo-controlled prospective study to reach a definite conclusion.

[Gilles de la Tourette Syndrome: Symptoms, Causes and Therapy]. / Gilles de la Tourette-Syndrom: Klinik, Ursachen, Therapie.

Gilles de la Tourette syndrome is a chronic neuropsychiatric movement disease with combined motor tics and at least one vocal tic for a minimum period of 1 year. It typically begins in the childhood (under 18 years of age).Most of the patients with Tourette syndrome have comorbidities, which often impair their quality of life more than the tics themselves.There are reported abnormalities in the cortico-striato-thalamo-cortical regions as well as in the neurotransmission of dopamine and other neurotransmission systems. Genetic and non genetic factors are discussed.In each patient psychoeducation is the basis of treatment. Specific treatment is only needed in more severe tic disorders which cause evident psychosocial impairment.Behavior therapy should be tried before drug treatment. For very severely affected adults, deep brain stimulation is a further treatment option.

Understanding the covariation of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms: A population-based adult twin study.

Chronic tic disorders (TD), attention-deficit/hyperactivity-disorder (ADHD), and obsessive-compulsive disorder (OCD) frequently co-occur in clinical and epidemiological samples. Family studies have found evidence of shared familial transmission between TD and OCD, whereas the familial association between these disorders and ADHD is less clear. This study aimed to investigate to what extent liability of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms is caused by shared or distinct genetic or environmental influences, in a large population-representative sample of Swedish adult twins (n = 21,911). Tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms showed modest, but significant covariation. Model fitting suggested a latent liability factor underlying the three phenotypes. This common factor was relatively heritable, and explained significantly less of the variance of attention-deficit/hyperactivity symptom liability. The majority of genetic variance was specific rather than shared. The greatest proportion of total variance in liability of tics, attention-deficit/hyperactivity, and obsessive-compulsive symptoms was attributed to specific non-shared environmental influences. Our findings suggest that the co-occurrence of tics and obsessive-compulsive symptoms, and to a lesser extent attention-deficit/hyperactivity symptoms, can be partly explained by shared etiological influences. However, these phenotypes do not appear to be alternative expressions of the same underlying genetic liability. Further research examining sub-dimensions of these phenotypes may serve to further clarify the association between these disorders and identify more genetically homogenous symptom subtypes. © 2016 Wiley Periodicals, Inc.

Neuroimaging of tic genesis: Present status and future perspectives.

Tics are hyperkinetic movements that are distinctive by their variety in semiology and duration and by their ability to be modulated by cognitive control. They are the hallmark of Gilles de la Tourette syndrome. Despite the variety of clinical presentations in this syndrome, dysfunction of cortico-striato-pallido-thalamo-cortical networks is suggested as a core pathophysiological mechanism. We review recent structural and functional neuroimaging studies that focused on the anatomical substrate of tics and their possible genesis. These studies showed a consistent relationship between structural and functional abnormalities within motor cortico-basal ganglia circuits and occurrence of tics. The failure of top-down cortical control over motor pathways because of the atypical trajectory of brain development could be a possible mechanism of tic genesis. Occurrence of tics results in several adaptive mechanisms, including modification of cortico-striatal network activity (reduced functional activation of the primary motor cortex) and neurochemical (increased γ-aminobutyric acid concentrations in the supplementary motor area) and microstructural white matter pathways rearrangements.

Serial pharmacological prescribing practices for tic management in Tourette syndrome.

Pharmacological treatments for Tourette syndrome (TS) vary in efficacy between different patients. The evidence base is limited as even high quality controlled studies tend to be of relatively short duration which may lose relevance in clinical usage. Patients are frequently treated with serial agents in the search for efficacy and tolerability. The success of this strategy has not been previously documented. We examined 400 consecutive TS patients seen over a 10-year period, some with a longer prior history in other clinics; 255/400 (64%) were prescribed medication. We present this heterogeneous cohort in terms of the number of drugs they had tried, and as a proxy measure of some benefit of the last drug used, whether it had been prescribed under our supervision for ≥ 5 months. The most commonly prescribed medications were aripiprazole (64%), clonidine (40%), risperidone (30%) and sulpiride (29%) with changes in prescribing practises over the period examined. The number of different drugs tried were one (n = 155), two (n = 69), three (n = 36), four (n = 14), five (n = 15), six (n = 5), seven (n = 2) and eight (n = 1). The data illustrate the difficulty in drug treatment of tics and suggest that even after trials of several agents there is potential benefit in trying further options.

Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS.

Streptococcal infections of skin and PANDAS.

Group A streptococcal infections are associated with a variety of infections and a subset of obsessive-compulsive disorder and/or tic disorders. Screening of obsessive-compulsive symptoms and tics in patient with streptococcal infection of skin must be effective in identifying subjects who met published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

Biofeedback treatment for Tourette syndrome: a preliminary randomized controlled trial.

OBJECTIVE: To study the clinical effectiveness of biofeedback treatment in reducing tics in patients with Tourette syndrome. BACKGROUND: Despite advances in the pharmacologic treatment of patients with Tourette syndrome, many remain troubled by their tics, which may be resistant to multiple medications at tolerable doses. Electrodermal biofeedback is a noninvasive biobehavioral intervention that can be useful in managing neuropsychiatric and neurologic conditions. METHODS: We conducted a randomized controlled trial of electrodermal biofeedback training in 21 patients with Tourette syndrome. RESULTS: After training the patients for 3 sessions a week over 4 weeks, we observed a significant reduction in tic frequency and improved indices of subjective well-being in both the active-biofeedback and sham-feedback (control) groups, but there was no difference between the groups in these measurements. Furthermore, the active-treatment group did not demonstrably learn to reduce their sympathetic electrodermal tone using biofeedback. CONCLUSIONS: Our findings indicate that this form of biofeedback training was unable to produce a clinical effect greater than placebo. The main confounding factor appeared to be the 30-minute duration of the training sessions, which made it difficult for patients to sustain a reduction in sympathetic tone when their tics themselves were generating competing phasic electrodermal arousal responses. Despite a negative finding in this study, electrodermal biofeedback training may have a role in managing tics if optimal training schedules can be identified.