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Background: Comorbid functional tic-like behaviors (FTB) have been described only rarely in patients with Tourette syndrome (TS)., Objectives: We present the first large sample of patients suffering from TS and FTB to raise awareness of this clinical presentation and to guide how to differentiate one from the other., Methods: We analyzed clinical data of 71 patients (n = 27 [38.0%] female, mean age: 21.5, range: 11-55) with TS + FTB., Results: In the majority of patients, FTB started abruptly on average 15 years after tic onset with "treatment-resistant" complex movements and ("coprophenomena-like") vocalizations preceded by timely related psychological stressors. Psychological evaluation revealed evidence for internal conflicts (79%), emotional dysregulation (56%), and maintaining factors (70%). About one third of patients had a positive history for further medically unexplained symptoms. Compared to a large TS sample (n = 1032), patients with TS + FTB were more likely to be female, and presented significantly more common with "coprophenomena-like" symptoms, atypical influential factors, atypical descriptions of premonitory sensations, and higher rates of comorbid obsessive-compulsive disorder and "self-injurious" behavior., Conclusions: Based on our data it can be assumed that FTB is a common comorbidity in TS, similar to functional overlay in other movement disorders and epilepsy. Before classifying a patient as suffering from treatment-resistant TS, FTB should be ruled out., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background and Purpose: Until the outbreak reported during the COVID-19 pandemic, functional tics were considered to be a relatively rare clinical phenotype, as opposed to other functional movement disorders such as functional tremor and dystonia. To better characterize this phenotype, we compared the demographic and clinical characteristics of patients who developed functional tics during the pandemic and those of patients with other functional movement disorders., Methods: Data from 110 patients were collected at the same neuropsychiatry centre: 66 consecutive patients who developed functional tics without other functional motor symptoms or neurodevelopmental tics and 44 patients with a mix of functional dystonia, tremor, gait, and myoclonus., Results: Both groups were characterized by female sex preponderance (70%-80%) and (sub)acute onset of functional symptoms (~80%). However, patients with functional tics had a significantly earlier age at onset of functional symptoms (21 vs. 39 years). Exposure to relevant social media content was reported by almost half of the patients with functional tics, but by none of the patients with other functional movement disorders. Comorbidity profiles were similar, with relatively high rates of anxiety/affective symptoms and other functional neurological symptoms (nonepileptic attacks)., Conclusions: Patients who developed functional tics during the pandemic represent a phenotypic variant of the wider group of patients with functional movement disorders, associated with younger age at onset and influenced by pandemic-related factors, including increased exposure to specific social media content. Diagnostic protocols and treatment interventions should be tailored to address the specific features of this newly defined phenotype., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Among adults with Tourette syndrome, depression and anxiety symptoms are widely prevalent and consistently associated with poor quality of life. Important knowledge gaps remain regarding mood and anxiety dimensions of the adult Tourette syndrome phenotype. Taking a dimensional approach, this study sought to determine the prevalence, severity, and clinical correlates of depression and anxiety symptoms in a clinical sample of adults with Tourette syndrome and other chronic tic disorders., Methods: A retrospective chart review was conducted of all adults with a chronic tic disorder presenting to a tertiary care Tourette syndrome clinic between December 2020 and July 2022. Information extracted during chart review included data from scales administered as part of routine care: Quality of Life in Neurological Disorders (Neuro-QoL) Depression Short Form, Neuro-QoL Anxiety Short Form, Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale, Dimensional Obsessive-Compulsive Scale, and Yale Global Tic Severity Scale. Relationships between variables were examined by conducting between-group, correlation, and multivariable regression analyses., Results: Data from 120 adult patients with a chronic tic disorder (77 men and 43 women) were analyzed. Neuro-QoL Anxiety scores were elevated in 66% of the cohort; Neuro-QoL Depression scores were elevated in 26%. Neuro-QoL Anxiety scores were significantly higher than general population norms, whereas Neuro-QoL Depression scores were not. After adjustment for covariates, depressive and anxiety symptom severity scores were significantly associated with each other and with obsessive-compulsive disorder symptom severity but not with tic severity. Sex-based differences emerged in the analyses., Conclusions: Among adults with chronic tic disorder, anxiety symptoms were more prevalent and severe than depressive symptoms, co-occurring psychiatric symptoms were more tightly linked with each other than with tic severity, and sex-based differences were evident., Competing Interests: Dr. Isaacs has received grant funding from Teva Branded Pharmaceutical Products, Research and Development. Dr. Riordan has received an educational grant from Medtronic. The other authors report no financial relationships with commercial interests.

Background and Purpose: Developmental stuttering and Tourette syndrome (TS) are common neurodevelopmental disorders. Although disfluencies may co-occur in TS, their type and frequency do not always represent pure stuttering. Conversely, core symptoms of stuttering may be accompanied by physical concomitants (PCs) that can be confused for tics. This scoping review aimed to explore the similarities and differences between stuttering and tics in terms of epidemiology, comorbidities, phenomenology, evolution, physiopathology, and treatment. We also described the nature of PCs in stuttering and disfluencies in TS., Methods: A literature search on Medline, Embase and PsycInfo was executed in March 2022. From 426 studies screened, 122 were included in the review (a majority being narrative reviews and case reports)., Results: TS and stuttering have several epidemiological, phenomenological, comorbidity, and management similarities suggesting shared risk factors and physiopathology (involving the basal ganglia and their connections with speech and motor control cortical regions). PCs in stuttering commonly involve the face (eyelids, jaw/mouth/lip movements) and sometimes the head, trunk and limbs. PCs can be present from early stages of stuttering and vary over time and within individuals. The function of PCs is unknown. Some individuals with TS have a distinct disfluency pattern, composed of a majority of typical disfluencies (mostly between-word disfluencies), and a mix of cluttering-like behaviors, complex phonic tics (e.g. speech-blocking tics, echolalia, palilalia), and rarely, atypical disfluencies., Conclusion: Future investigations are warranted to better understand the complex relationships between tics and stuttering and address the management of disfluencies in TS and PCs in stuttering., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: An unprecedented increase in newly developed functional tics, mainly in young females, has been reported during the COVID-19 pandemic. We set out to complement existing case series with the largest controlled study to date on the clinical phenomenology of functional tics versus neurodevelopmental tics., Methods: Data from 166 patients were collected at a specialist clinic for tic disorders during a three-year period overlapping with the COVID-19 pandemic (2020-2023). We compared the clinical features of patients who developed functional tics during the COVID-19 pandemic (N = 83) to patients with Tourette syndrome matched for age and gender (N = 83)., Results: Female adolescents and young adults accounted for 86% of the clinical sample of patients with functional tics, who were less likely to report a family history of tic disorders than their matched controls with Tourette syndrome. Co-morbidity profiles were significantly different: anxiety and other functional neurological disorders were more strongly associated with functional tics, whereas attention-deficit and hyperactivity disorder and tic-related obsessive-compulsive behaviors co-occurred more frequently with neurodevelopmental tics. Overall, absence of tic-related obsessive-compulsive behaviors (t = 8.096; p < 0.001) and absence of a family history of tics (t = 5.111; p < 0.001) were the strongest predictors of the diagnosis of functional tics. Compared to neurodevelopmental tics, functional tics were more likely to present acutely/subacutely at a later age (21 versus 7 years), without a clear rostro-caudal progression. Coprophenomena, self-injurious behaviors, and complex clinical manifestations such as blocking tics, throwing tics, and tic attacks, were all over-represented in the functional group., Conclusions: Our findings provide robust confirmation of both patient-related variables and tic characteristics contributing to the differential diagnosis between functional tics developed during the pandemic and neurodevelopmental tics reported by patients with Tourette syndrome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The COVID-19 pandemic has been associated amongst other things with a sharp increase in adolescents and young adults presenting acutely with functional tics. Initial reports have suggested clinically relevant differences between functional tics and neurodevelopmental tics seen in primary tic disorders such as Tourette syndrome. We aimed to provide confirmatory findings from the largest single-centre cohort to date., Methods: In the present study we present data from 105 consecutive patients who developed functional tics during a 3-year period overlapping with the COVID-19 pandemic (April 2020-March 2023). All patients underwent a comprehensive neuropsychiatric assessment at a single specialist centre for tic disorders., Results: Female adolescents and young adults accounted for 69% of our sample. Functional tics had an acute/subacute onset in most cases (75% with a peak of severity within 1 month). We found a disproportionately high frequency of complex movements (81%) and vocalizations (75%). A subset of patients (23%) had a pre-existing primary tic disorder (Tourette syndrome with functional overlay). The most common psychiatric co-morbidities were anxiety (70%) and affective disorders (40%). Moreover, 41% of patients had at least one functional neurological disorder in addition to functional tics. Exposure to tic-related social media content was reported by half of the patients., Conclusions: Our findings confirm substantial clinical differences between functional tics developed during the pandemic and neurodevelopmental tics. Both patient- and tic-related red flags support the differential diagnostic process and inform ongoing monitoring in the post-pandemic era., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

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 (N cases  = 612; N controls  = 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., (© 2022 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Background: Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder with a worldwide prevalence of about 0.3-1% of the population. During the pandemic caused by SARS-CoV-2 infection, the impact on the mental health of children and adolescents was very important. The persistence of symptoms in the post-acute phase of the disease has been termed Long COVID. The neuropsychiatric symptoms seem to be the most common impairment in children and adolescents with long COVID., Objectives: Considering the impact of pandemic on mental health, in this study we analyzed the long-term effects of SARS-CoV-2 infection in children and adolescents affected by TS., Methods: We conducted an online questionnaire covering socio-demographic and clinical data among 158 patients affected by TS or chronic tic disorders (CTD), of which 78 participants reported a positive SARS-CoV-2 infection. Data were collected to investigate tic severity and both the comorbidities, as well as lockdown-related changes to daily life activities and, in case of infection of SARS-CoV-2, possible symptoms of acute infection and long COVID. Markers of systemic inflammation including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, iron, electrolytes, white blood cell counts, platelet cell counts levels, markers of liver, kidney and thyroid function were analyzed. First, all patients were screened with the Schedule for affective disorders and Schizophrenia for School age children-present and lifetime (Kiddie-SADS-PL) to rule out primary psychiatric disorders considered as criteria of exclusion. Then, all patients were clinically assessed at baseline (T0), and after three months (T1) through the administration of Yale Global Tic Severity Rating Scale (YGTSS), Multidimensional Anxiety Scale for Children (MASC), Child Depression Inventory (CDI) and Child Behavior Checklist (CBCL)., Results: Among the cohort of TS patients that contracted SARS-CoV-2 infection, 84.6% (n = 66) experienced any acute symptoms, and long COVID symptoms occurred in 38.5% (n = 30). A worsening of clinical symptoms of tics and eventually associated comorbidities occurred in 34.6% (n = 27) of TS patients that contracted SARS-CoV-2 infection. TS patients with or without SARS-CoV-2 infection showed an increase in the severity of tics and also behavioral, depressive and anxious symptoms. Instead, this increase was more evident in patients who contracted the infection than in patients who did not contract it., Conclusions: SARS-CoV-2 infection may have a role in the increase of tics and associated comorbidities in TS patients. Despite of these preliminary results, further investigations are necessary to improve knowledge about the acute and long-term impact of SARS-CoV-2 in TS patients., (© 2023. The Author(s).)

Background: Previous studies have shown that Tourette syndrome (TS) has an impact on academic achievements. The aim of this study was to investigate the association between the severity of tics and comorbidities and educational outcomes., Methods: From 2005 to 2007, 395 participants were included in a large cohort (314 with TS and 81 controls) and the mean age was 12.60 ± 2.64 years. The cohort was re-examined after 4 to 8 years (median 5.6) where n  = 276 participants (223 with TS and 53 controls) were included with a mean age of 18.52 ± 2.73 years. At both time points, severity of tics and the presence and severity of psychiatric comorbidity were assessed. Educational achievements were assessed through structured interviews., Results: Children with TS had a lower passing rate at lower secondary and high school compared to healthy controls. More severe vocal tics were associated with fewer passing lower secondary school at a prospective level. At a cross-sectional level, more severe motor tics were associated with fewer passing high school. Tic severity only influenced children with TS without comorbidity. The severity of comorbidity was found to be associated with the educational level at a longitudinal view, but not cross-sectional., Conclusion: Overall, children with TS had a lower passing rate at lower secondary school and high school compared to healthy controls. We found that this difference was more likely driven by the severity of comorbidities than tic severity. It is important to be aware of academic achievement in children with TS in order to give them the right support and thereby optimize educational opportunities., Competing Interests: None declared., (Thieme. All rights reserved.)

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., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Tic disorders (TD) are complex neuropsychiatric disorders frequently associated with a variety of comorbid problems, whose negative effects may exceed those of the tics themselves. In this study, we aimed to explore the sociodemographic and clinical characteristics of children with TD and behavioral problems, and develop a prediction model of behavioral problems based on the predictors under real-world conditions., Methods: A hospital-based cross-sectional study was conducted on children with TD. Behavioral problems were surveyed using the Achenbach Child Behavior Checklist (CBCL). Sociodemographic information was collected from face-to-face interviews using an electronic questionnaire administered during the initial ambulatory visit. Clinical data were collected from medical records, and quality control was performed. The sociodemographic and clinical characteristics of patients with and without behavioral problems were statistically compared, and a nomogram prediction model was developed based on multivariate logistic regression analysis. The discriminatory ability and clinical utility of the nomogram were assessed by concordance index (C-index), receiver operating characteristic (ROC) curve, decision curve analysis (DCA) and clinical impact curve (CIC)., Results: A total of 343 TD cases were included in the final analysis, of which 30.32% had behavioral problems. The prediction model showed age 12-16 years, abnormal birth history, parenting pattern of indulgence, parent/close relatives with psychiatric disorders, chronic motor or vocal tic disorder (CTD)/Tourette syndrome (TS) and moderate/severe tic severity were associated with behavioral problems in children with TD. The C-index of the prediction model (nomogram) was 0.763 (95% confidence interval, 0.710 ~ 0.816). The nomogram was feasible for making beneficial clinical decisions, according to the satisfactory results of the DCA and CIC., Conclusions: A nomogram prediction model for comorbid behavioral problems in children with TD was established. The prediction model demonstrated a good discriminative ability and predictive performance for beneficial clinical decisions. This model further provides a comprehensive understanding of associated sociodemographic and clinical characteristics by visual graphs and allows clinicians to rapidly identify patients with a higher risk of behavioral problems and tailor necessary interventions to improve clinical outcomes., (© 2023. The Author(s).)

Background: Few studies have estimated the real prevalence of neurodevelopmental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in Spain and worldwide. However, there are disparate prevalence figures. We consider research in this field essential to improve early detection, secondary prevention, and health planning., Methods: The Minikid ADHD and TICS-Mini International Neuropsychiatric Interview for Children and Adolescents, the Autism Spectrum Quotient (Children's version, AQ- Child) and a protocol of general medical questions were administered for screening purposes. The PROLEXIA battery for children aged from 4 to 6 years was used for direct assessments. Parents provided information on emotional, medical, and school aspects. The final population evaluated using these tools consisted of 291 6-year-old subjects., Results: The overall risk of presenting with a neurodevelopmental disorder was 55.4%. A 23.4% risk of presenting with attention-deficit/hyperactivity disorder (ADHD) in any modality (inattentive, hyperactive-impulsive and combined), a 2.8% risk of developing autism spectrum disorder (ASD), a 30.6% risk of presenting with a learning disorder with reading difficulties, a 5.5% risk of tics and a 22.5% risk of language problems (incomprehensible language or minor language problems) were detected in the sample. The most common combination of disorders was learning and language difficulties, accounting for 6.9% of the sample. The second most frequent combination was the presence of learning and language difficulties and ADHD, accounting for 4.5% of the sample., Conclusions: The prevalence of risks detected in our sample seems to be consistent with national and international studies. A significant proportion of our sample had never been previously diagnosed (85%), so early detection programs are recommended., (© 2023. The Author(s).)

Objective: To evaluate the prevalence of nail biting in child and adolescent outpatients at a single institution and the chronological relationship between nail biting and tics in patients with Tourette syndrome (TS) with or without attention-deficit hyperactivity disorder (ADHD)., Design: Retrospective observational study., Setting: Teaching hospital in Taiwan., Participants: All participants were aged 4-18 years, including 535 patients with TS, 230 patients with provisional tic disorder and 1460 patients without neurological or psychiatric disorders (controls)., Outcome Measures: Presence of nail biting, starting age for nail biting and starting age for motor and/or vocal tics., Results: Nail biting was more commonly observed in patients with TS (56.6%) than in patients with provisional tic disorder (27.4%) or controls (15.0%), regardless of sex (all p<0.020). Nail biting was also more common in patients with TS with ADHD than in those without (75.0% vs 47.6%; p<0.001), but the starting age was significantly later in those with concomitant ADHD than without (5.3 vs 3.8 years; p<0.001). In patients with TS, the onset of nail biting occurred earlier than that of tics, regardless of ADHD status., Conclusion: Nail biting was more prevalent and occurred earlier than tics in patients with TS, regardless of ADHD status, in the study population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: With a lifetime prevalence of 2.3%, obsessive compulsive disorder is a chronic, disabling condition that is associated with significant social and occupational impairment. Up to 30% of individuals with obsessive-compulsive disorder have a lifetime diagnosis of tic disorders. Antiseizure medication is increasingly used for a variety of physical and psychiatric illnesses. Clarification of the relationship between these symptoms/disorders and use of antiseizure medication is critically important for diagnostic and treatment purposes., Areas Covered: Studies on antiseizure-induced obsessive-compulsive disorder and tic disorders are reviewed. The literature search strategy identified 89 articles. Twenty-nine articles were included in the final results. Of these, 24 are case reports or case studies, 2 cross-sectional studies, 1 chart review, 1 population-based case-control study and 1 observational prospective study assessing lamotrigine, levetiracetam, topiramate, zonisamide, and carbamazepine., Expert Opinion: This study highlighted the temporal relationship of antiseizure medication use and onset of obsessive-compulsive symptoms and tics. Monitoring for medication-induced obsessive compulsions or tics should be undertaken when prescribing antiseizure medication for treatment of mood disorders or epilepsy. Further research identifying the causal relationship between antiseizure medication and de novo onset of obsessive-compulsive symptoms, obsessive-compulsive disorder and tic disorder is required.

Introduction: Tourette syndrome (TS) is characterized by the presence of motor and phonic tics, as well as a variety of behavioral co-morbidities. Self-injurious behavior (SIB) is one of the most serious manifestations of TS, but its pathophysiology is poorly understood., Methods: Consecutive patients with TS studied in a tertiary care center., Results: We identified a total of 34 patients (16.9%) with SIB from a cohort of 201 patients with TS. Most of these patients (n = 23, 11.4%) experienced self-directed damage; while others had outward-directed (n = 7, 3.5%) or tic-related SIB (n = 4, 2%). Compared to other patients with TS, those who manifested SIB (self- and outward-directed damage) were more likely to have tics involving shoulder (P = 0.046), trunk (P = 0.006), and arm (P = 0.017); as well as dystonic tics (P = 0.016); complex motor tics (P < 0.001), copropraxia (P = 0.045), complex phonic tics (P = 0.003), higher number of phonic tics (P = 0.001), verbalizations (P = 0.001), coprolalia (P = 0.006) and obsessive compulsive disorder (OCD) (P < 0.001) as determined by bivariate analysis. In the multivariate analysis only complex motor tics (P = 0.006), obsessive-compulsive behavior (P = 0.025) and greater severity of tics (P = 0.002) showed a statistically significant association with SIB. Patients with SIB had a greater probability of being selected for deep brain stimulation (DBS) therapy by the treating clinician (P = 0.01)., Conclusions: SIB is observed in about 17% of patients with TS. The presence of complex motor tics, OCD and greater severity of tics was related to the presence of SIB., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To investigate sex-related differences in tic severity, tic-related impairments, and psychiatric comorbidities in childhood., Method: In this cross-sectional study, tic severity/impairment and demographic factors were collected from 270 children and young people (aged 5-17y, mean 10y 6mo, SD 3y 4mo; 212 males and 58 females) with a tic disorder diagnosis at a specialty clinic. Psychiatric diagnoses and corresponding screening questionnaire scores were collected for attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), major depressive disorder, and anxiety disorders. Logistic regression was used to compare the effect of sex and age on psychiatric comorbid diagnoses. The Mann-Whitney U test and t-tests were used to assess differences in questionnaire score distribution between sexes., Results: Females had more severe motor tics (12.55 vs 10.81, p=0.01) and higher global severity scores (38.79 vs 32.66, p=0.03) on the Yale Global Tic Severity Scale. Females were less likely to be diagnosed with ADHD (odds ratio=0.48, 95% confidence interval=0.26-0.89). No significant sex difference was observed in diagnosis rates or symptom severity scores for anxiety or OCD. Females had significantly higher scores than males on the Children's Depression Inventory, Second Edition., Interpretation: The higher level of motor tic severity and global severity in females further supports the differential natural history of tic disorders in females. Females with tic disorders may be underdiagnosed for ADHD., (© 2021 Mac Keith Press.)

Background: The lifetime prevalence of obsessive - compulsive disorder (OCD) is currently estimated at 2 - 3% and the prevalence in first-degree family members is estimated to range between 10 and 11%. Separating OCD from other anxiety disorders and including it into the new "obsessive - compulsive and related disorders" (OCRDs) category has had a dramatic impact on the diagnosis, while also contributing to the better understanding of the genetics of these disorders. Indeed, grouping OCD with body dysmorphic disorder (BDD), and body-focused repetitive behaviors such as trichotillomania (hair pulling), onychophagia (nail biting), and excoriation (skin picking) into the same diagnostic family has resulted in a much greater lifetime prevalence (> 9%). These diagnostic changes necessitate an updated epidemiological study, thus motivating this investigation., Methods: The study sample comprised of 457 patient's cases from an Israeli and an Australian OCD center. Interviews were completed as a part of the intake or during treatment in each of the centers. Prevalence of OCD, OCRDs, tics, and other psychiatric comorbidities in first- and second-degree relatives was assessed by interviewing the OCD patients. Interviews were conducted by at least two researchers (LC, OBA, JZ) and only family information on which the interviewers have reached consensus was considered., Results: Initial analyses revealed an increase of OCD and OCRD prevalence in first- and second-degree family members as compared to the current literature due to reclassification of these disorders in DSM-5., Conclusion: The new category of OCRD has changed the landscape of epidemiological studies in OCD. Further and broader studies are needed in order to better understand the lifetime prevalence of OCRD in first- and second-degrees family member., (© 2022. The Author(s).)

Background and Objectives: The goal of this work was to investigate the association between group A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTDs)., Methods: In a prospective cohort study, children with no history for tics who were 3 to 10 years of age with a first-degree relative with a CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centers. Presence of GAS infection was assessed with throat swabs, serum anti-streptolysin O titers, and anti-DNAse titers blinded to clinical status. GAS exposure was defined with 4 different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted with Cox regression and logistic regression analyses., Results: A total of 259 children were recruited; 1 child was found to have tic onset before study entry and therefore was excluded. Sixty-one children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an ≈60% lower risk of developing tics compared to boys (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.2-0.7). However, there was no statistical evidence to suggest an association of any of the 4 GAS exposure definitions with tic onset (GAS exposure definition 1: HR 0.310, 95% CI 0.037-2.590; definition 2: HR 0.561, 95% CI 0.219-1.436; definition 3: HR 0.853, 95% CI 0.466-1.561; definition 4: HR 0.725, 95% CI 0.384-1.370)., Discussion: These results do not suggest an association between GAS exposure and development of tics., Classification of Evidence: This study provides Class I evidence that group A streptococcal exposure does not associate with the development of tics in children with first-degree relatives with chronic tic disorder., (© 2022 American Academy of Neurology.)

Background: Children with Tourette syndrome (TS) often have comorbid disorders, particularly attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). While subtle premorbid symptoms have been described in various psychiatric disorders, the presence of clinical precursors that may exist before the onset of tics is unknown. This longitudinal study aimed to find clinical precursors of tics by assessing a range of clinical characteristics prior to tic onset in comparison with children without onset of tics., Methods: A sample of 187 3- to 10-year-old first-degree unaffected relatives of children with TS were followed up to 7 years in the European Multicentre Tics in Children Study (EMTICS). We investigated whether clinical characteristics assessed at baseline predicted tic onset, comparing 126 children without tic onset to 61 children who developed tics. We used the least absolute shrinkage and selection operator (LASSO) method, a penalised logistic regression approach. We also explored sex differences and repeated our analyses in an age- and sex-matched subsample., Results: Children with tic onset were more frequently male (β = -0.36), had higher baseline severity of conduct problems (β = 0.23), autism spectrum disorder symptoms (ASD; β = 0.08), compulsions (β = 0.02) and emotional problems (β = 0.03) compared to children without tic onset. Conduct and ASD problems were male-specific predictors, whereas severity of compulsions and oppositional (β = 0.39) and emotional problems were female-specific predictors., Conclusion: This study supports the presence of clinical precursors prior to tic onset and highlights the need of sex-specific monitoring of children at risk of developing tics. This may aid in the earlier detection of tics, particularly in females. We moreover found that tics most often persisted one year after tic onset, in contrast to the common belief that tics are mostly transient., (© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background and Aim: Clinical centres have seen an increase in tic-like movements during the COVID-19 pandemic. A series of children and adolescents are described., Methods: A retrospective chart review of 34 consecutive paediatric patients presenting with sudden onset tic-like movements, seen over 6 months., Results: 94% of patients were female, with an average age of sudden onset or increase of tic-like movements of 13.7 years. 44% had a previous diagnosis of tics, and 47% initially presented to an emergency department. Comorbid psychiatric and neurodevelopmental disorders were reported in 91% with 68% reporting anxiety., Conclusion: We highlight a dramatic presentation of sudden onset functional tic-like movements in predominantly female adolescents to help inform identification and management. There is need to research the neurobiological underpinnings and environmental exacerbating factors leading to these presentations and to explore effective therapeutic strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. Because of its varied clinical expressions and lack of reliable diagnostic biomarker, present TS diagnosis still depends on qualitative descriptions of symptoms. Our study aimed to investigate whether the complexity of resting state brain activity can serve as a potential biomarker for TS diagnosis, since it has been used successfully in various neuropsychiatric disorders, including two common TS comorbidities: attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). In the current study, we used both univariate analysis and multivariate searchlight analysis with both linear and non-linear classification methods to explore the group differences in the complexity of resting state brain blood oxygen level-dependent (BOLD) signals between 25 TS boys without comorbidity and 25 sex, age and educational years matched healthy controls (HCs). We also investigated the relation between symptom severity in TS patients (YGTSS scores) and complexity indices derived from different analysis methods. We found: i) univariate analysis revealed reduced complexity in TS patients in the left cerebellum, left superior frontal gyrus, and left medial frontal gyrus; ii) multivariate analysis with non-linear classification method achieved the highest performance (accuracy: 0.94, sensitivity: 0.96, specificity: 0.92, AUC: 0.95) in bilateral supplementary motor areas; iii) significant correlations were found between complexity index derived from multivariate analysis with non-linear classification method and Tic severity (YGTSS scores) in the left cerebellum (r = 0.523, with YGTSS phonic) and in the right supplementary motor area (r = 0.767, with YGTSS motor). Taken together, these results suggested that complexity of resting state BOLD activity is a highly effective index for differentiating TS patients from normal controls. It has a good potential to be a quantitative biomarker for TS diagnosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

During 2020, an increase of functional tics in children and adolescents has been observed. In this review, we present phenotypes, differential diagnosis and treatment for functional tics. We discuss potential contributing causes, like the COVID-19 pandemic and the focus on tics on social media. Functional tics are more complex than tics seen in Tourette syndrome and develop more suddenly in relation to stressors mainly in teenage girls. Psychosocial issues and comorbidities must be addressed and treated by a multidisciplinary team through psychoeducation and if necessary, cognitive-behavioural therapy.

Introduction: Tourette Syndrome (TS) is a common disorder with chronic motor and phonic tics, associated with neuropsychiatric comorbidities., Objective: To characterize clinical-demographic variables, comor bidities, and management in a pediatric cohort with TS and compare them according to sex., Patients and Method: A retrospective cohort of patients < 18 years old with TS followed up between 2000 and 2018 was evaluated. Clinical records were reviewed obtaining variables of age, sex, reason for consul tation, age of onset, type and complexity of tics, follow-up time, family history, obsessive behaviors, neuropsychiatric and psychopathological comorbidity, neurological disorders, and pediatric mor bidity. Studies and treatments performed, and management used were also recorded., Results: 126 patients were included, aged between 4-18 years, 103 males (sex F:M ratio = 4.5:1), with a follow-up of 4.8 ± 1.9 years. The mean age of tic onset and TS diagnosis was 6.5 ± 2.2 and 9.4 ± 2.7 years, res pectively, and a diagnostic latency of 2.8 ± 2.2 years. The first consultation in the total of girls was due to tics, in contrast to the boys of whom 14.6% (n = 15) consulted due to comorbidities. There was 38.9% of tics and 8,7% of TS. Neuropsychiatric comorbidities were frequent, recorded in 69.8%, with Attention Deficit Disorder (43.6%) and Obsessive-Compulsive Disorder (20.6%) standing out.110 cases (87.3%), received pharmacological therapy and 54.4% required three or more drugs at some point in their evolution. Only in 16 cases (12.7%), no pharmacological therapy was required, only psychoeducation in 7 (5.6%) cases, and behavioral therapy in 9 cases (7.1%)., Conclusions: The cli nical characteristics of our children with TS are similar to international descriptions, highlighting that in the group of boys, the first consultation could be due to comorbidity, recognizing later the presence of tics. Although psychoeducation and behavioral therapies are recommended as first-line management, most of the patients in this group required pharmacological therapy.

Background and Purpose: Clinicians have reported an increase in functional tic-like behaviours in children and youth during the COVID-19 pandemic. We describe adults developing rapid onset of functional tic-like behaviours between May 2020 and June 2021., Methods: Data were analysed from the Adult Tic Disorders Registry, a single-site,12-month prospective cohort study that began enrolment in January 2021. We compared clinical features of participants with Tourette syndrome or persistent motor/vocal tic disorder to participants with rapid onset tic-like behaviours., Results: Thirty-three participants registered between January and June of 2021; nine had rapid onset tic-like behaviours, and 24 had Tourette syndrome or persistent motor tic disorder. Participants with rapid onset tic-like behaviours were younger (19.9 vs. 38.6 years, p = 0.003), had older age at onset (15.3 vs. 10.1, p = 0.0009), and were more likely female (p < 0.0001). They had higher motor and vocal tic severity and impairment scores (all p < 0.01) and were more likely to have complex arm/hand motor tics (p < 0.0001), complex vocal tics (p < 0.0001), and coprolalia (p = 0.004). They had significantly higher scores on all mental health symptom self-report measures (all p < 0.05) and were significantly more likely to be diagnosed with depression (p = 0.03)., Conclusions: The clinical features that help differentiate rapid onset tic-like behaviours from Tourette syndrome or persistent motor tic disorder include their phenomenology, onset age, and clinical course. Rapid onset tic-like behaviours are a distinct subtype of functional neurological disorder that has emerged during the COVID-19 pandemic in young people and appears to be strongly socially influenced., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Tic disorders belong to the broad spectrum of pediatric and adult movement disorders. The wide variability in clinical presentations, applied assessment tools, and treatments are poorly understood., Objectives: To map practices and knowledge base of movement disorder clinicians concerning clinical features, pathophysiology, and treatment approaches in tic disorders., Methods: A 33-item survey was developed by the Tic Disorders and Tourette syndrome Study Group members of the Movement Disorder Society. The survey was distributed to the complete society membership and included responses from 346 members, 314 of whom reported treating tic disorders., Results: Approximately one third of survey respondents (35%) frequently evaluated patients with tics. The data revealed widespread use of existing guidelines (about 70%) and screening for comorbid disorders (>90%). The most common investigations used to rule out secondary causes of tics were imaging (92%), laboratory tests (66%) and neurophysiology (38%). Functional tics were the second most common tic etiology following primary tics. Only 27% of respondents reported confidence in knowledge about tic pathogenesis. Top rated interventions to treat tics were psychoeducation, cognitive behavioral intervention for tics (CBIT) and treatment for neuropsychiatric comorbidities. Antipsychotics were ranked as the most effective pharmacologic tic intervention., Conclusions: The majority of movement disorders specialists do not frequently encounter tics. There was sparse knowledge about tic pathophysiology. Psychoeducation, CBIT, the treatment of neuropsychiatric comorbidities and use of antipsychotics emerged as the most common interventions to treat tics. These results provide insight into what will be needed to improve the diagnosis and treatment of tic disorders., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Background: Obsessive-compulsive disorder (OCD) and tic disorder (TD) represent highly disabling, chronic and often comorbid psychiatric conditions. While recent studies showed a high risk of suicide for patients with OCD, little is known about those patients with comorbid TD (OCTD). Aim of this study was to characterize suicidal behaviors among patients with OCD and OCTD., Methods: Three hundred and thirteen outpatients with OCD (n = 157) and OCTD (n = 156) were recruited from nine different psychiatric Italian departments and assessed using an ad-hoc developed questionnaire investigating, among other domains, suicide attempt (SA) and ideation (SI). The sample was divided into four subgroups: OCD with SA (OCD-SA), OCD without SA (OCD-noSA), OCTD with SA (OCTD-SA), and OCTD without SA (OCTD-noSA)., Results: No differences between groups were found in terms of SI, while SA rates were significantly higher in patients with OCTD compared to patients with OCD. OCTD-SA group showed a significant male prevalence and higher unemployment rates compared to OCD-SA and OCD-noSA sample. Both OCTD-groups showed an earlier age of psychiatric comorbidity onset (other than TD) compared to the OCD-SA sample. Moreover, patients with OCTD-SA showed higher rates of other psychiatric comorbidities and positive psychiatric family history compared to the OCD-SA group and to the OCD-noSA groups. OCTD-SA and OCD-SA samples showed higher rates of antipsychotics therapies and treatment resistance compared to OCD-noSA groups., Conclusions: Patients with OCTD vs with OCD showed a significantly higher rate of SA with no differences in SI. In particular, OCTD-SA group showed different unfavorable epidemiological and clinical features which need to be confirmed in future prospective studies.

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation., Objective: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT., Methods: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature., Results: Rates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates., Conclusions: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: The association of stereotypies and tics is not rare in children with severe autism spectrum disorder (ASD). The differential diagnosis between stereotypies and tics in this patient population can be difficult; however, it could be clinically relevant because of treatment implications., Methods: A total of 108 video recordings of repetitive behaviors in young patients with stereotypies in the context of ASD were reviewed by a movement disorders expert and a trainee, in order to assess the prevalence of possible co-morbid tics. The Modified Rush Videotape Rating Scale (MRVS) was used to rate tic frequency and severity., Results: Out of 27 patients with stereotypies (24 males; mean age 14 years), 18 (67%) reported possible tics. The most frequently observed tics were eye blinking, shoulder shrugging, neck bending, staring, and throat clearing. The mean MRVS score was 5, indicating mild tic severity. The only significant difference between patients with tics and patients without tics was the total number of stereotypies, which was higher in the subgroup of patients without tics (p = 0.01)., Conclusions: Expert review of video-recordings of repetitive behaviors in young patients with ASD and stereotypies suggests the possibility of a relatively high rate of co-morbid tics. These findings need to be integrated with a comprehensive clinical assessment focusing on the diagnostic re-evaluation of heterogeneous motor manifestations.

Background: Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in cases of encephalitis resulting from a range of aetiologies., Objective: This review aimed to assess the prevalence and characteristics of tics in patients with encephalitis., Methods: We conducted a systematic literature review of original studies on the major scientific databases, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: In addition to the established association between tics and encephalitis lethargica, our literature search identified reports of tics in patients with immune-mediated pathologies (including autoimmune encephalitides affecting the N-methyl-D-aspartate receptor, voltage-gated potassium channels, and glycine receptors) and infective processes (ranging from relatively common viral pathogens, such as herpes simplex, to prions, as in Creutzfeldt-Jakob disease). Tics were most commonly reported in the post-encephalitic period and involvement of the basal ganglia was frequently observed., Discussion: The association of new-onset tics and encephalitis, in the background of other neuropsychiatric abnormalities, has practical implications, potentially improving the detection of encephalitis based on clinical features. Future research should focus on the categorisation and treatment of hyperkinetic movement disorders associated with encephalitis.

Background: Tic disorders are childhood-onset neuropsychiatric disorders characterized by multiple motor or vocal tics with frequent comorbidities and a broad spectrum of phenotypic presentations. In this study, we aimed to investigate the clinical characteristics and comorbid neuropsychiatric conditions in pediatric patients with tic disorders., Methods: We retrospectively reviewed the medical records of 119 pediatric patients (89 males, 30 females) who were diagnosed with tic disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) at Uijeongbu St. Mary's Hospital, Republic of Korea, between January 2012 and July 2019., Results: The mean age of tic onset was 6.9 years (range, 1-14) and the mean age at diagnosis was 8 years (range, 1-17). The mean lag between tic onset and diagnosis was 13.3 months (range, 0.25-132). The most common, first-presenting tics were eye blinking (50.4%), followed by jaw or lip movement (29.4%) and throat clearing (29.4%). Thirty-seven (31.1%) patients had at least one co-occurring neuropsychiatric disorder at the time of tic diagnosis. Subtypes of tic disorders, types of initial tics, and presence of neuropsychiatric comorbidities were not associated with tic severity. Tic severity was associated with greater functional impairment and tic noticeability (p < 0.05). A relatively shorter time to diagnosis was associated with tic severity (Spearman's ρ = - 0.14, p = 0.11)., Conclusions: The evolving nature of tic expression and severity, high prevalence of neuropsychiatric comorbidities, and associated functional impairments emphasize the importance of comprehensive assessment during the disease course for determining and prioritizing goals of treatment.

Background: Tourette syndrome (TS) and persistent motor/vocal tic disorders are neurodevelopmental conditions characterised by the chronic presence of motor and/or vocal tics. Patients with TS often present with co-morbid disorders, especially attention-deficit and hyperactivity disorder (which tends to improve after childhood), and obsessive-compulsive disorder (which can persist in adulthood). We set out to explore pharmacotherapy for tics in adult patients with TS and persistent motor/vocal tic disorders, as well as its relationship with the presence of co-morbid conditions., Methods: We retrospectively reviewed the clinical characteristics and pharmacotherapy of 192 adult patients with TS (n = 187), persistent motor tic disorder (n = 3) and persistent vocal tic disorder (n = 2) attending a specialist clinic in the UK., Results: Anti-dopaminergic medications (n = 65) and alpha-2-agonists (n = 50) were the most commonly prescribed pharmacotherapy for tic management. A sub-group analysis revealed that co-morbid obsessive-compulsive disorder and sub-threshold obsessive-compulsive behaviours were significantly more common in patients treated with anti-dopaminergic medications than patients taking alpha-2-agonists (p = 0.013 and p = 0.047, respectively)., Conclusions: The use of pharmacotherapy options for tic management observed at a specialist clinic for adults with TS reflects guideline recommendations. We found that the presence of co-morbid obsessive-compulsive disorder/behaviours correlates with the choice of anti-dopaminergic medications over alpha-2-agonists, in line with available evidence on the efficacy of anti-dopaminergic medications for the treatment of specific tic-related behavioural symptoms.

Objectives: While drug-induced tics have been described, in particular with neuroleptics, psychostimulants, or anti-epileptics, the strength and the direction of these associations are still debated. The aim of this study was to investigate the association between tics and drug exposure through a two-step analysis in two pharmacovigilance databases., Methods: We first performed a descriptive clinical analysis of cases registered in the French pharmacovigilance database (FPVD) from January 1985 to December 2018. We then performed a disproportionality analysis in VigiBase®, the WHO pharmacovigilance database, from January 1967 to June 2019, through the calculation of reporting odds ratio (ROR)., Results: The drugs most frequently associated with tics in the FPVD were methylphenidate, lamotrigine, montelukast, tramadol, mirtazapine, venlafaxine, aripiprazole, and risperidone. In VigiBase®, we found a significant ROR with methylphenidate (ROR 37.54, 95% confidence interval [CI] 34.81-40.48), montelukast (ROR 12.18, 95% CI 10.29-14.41), aripiprazole (ROR 7.40, 95% CI 6.35-8.62), risperidone (ROR 4.40, 95% CI 3.72-5.21), and venlafaxine (ROR 1.52, 95% CI 1.14-2.03)., Conclusion: This postmarketing study confirmed a potential harmful association with methylphenidate (the highest association, as expected), aripiprazole, risperidone, lamotrigine, and venlafaxine and, interestingly, found a strong signal with montelukast, which, to our knowledge, had never been published before., (© 2020 John Wiley & Sons Ltd.)

Introduction : Though many unanswered questions about the pathophysiology of Tourette Syndrome remain, several pharmacotherapies for tics have been studied, with varying results in terms of efficacy and the strength of evidence. Areas covered : This literature review encompasses pharmacotherapies for tics. The pharmacotherapies discussed in this review include: alpha agonists, antipsychotics, topiramate, botulinum toxin, and dopamine depleters. Expert opinion : Once the presence of tics is confirmed and psychoeducation and support are provided to patients and caregivers, one must examine the degree of tic-related impairment and the presence of psychiatric comorbidities. These factors influence treatment decisions as the presence of comorbidity and related impairment may shift the treatment target. When selecting a medication for tics, the presence of ADHD (the most frequent comorbidity) strengthens the case for choosing an alpha agonist. The case for antipsychotic medications is strongest when tic-related impairment is severe and/or the tics are refractory to more conservative measures. All medications require drug safety monitoring procedures and reevaluation over time.

Children with persistent (chronic) tic disorders (PTDs) experience impairment across multiple domains of functioning, but given high rates of other non-tic-related conditions, it is often difficult to differentiate the extent to which such impairment is related to tics or to other problems. The current study used the Child Tourette's Syndrome Impairment Scale - Parent Report (CTIM-P) to examine parents' attributions of their child's impairment in home, school, and social domains in a sample of 58 children with PTD. Each domain was rated on the extent to which the parents perceived that impairment was related to tics versus non-tic-related concerns. In addition, the Yale Global Tic Severity Scale (YGTSS) was used to explore the relationship between tic-related impairment and tic severity. Results showed impairment in school and social activities was not differentially attributed to tics versus non-tic-related impairment, but impairment in home activities was attributed more to non-tic-related concerns than tics themselves. Moreover, tic severity was significantly correlated with tic-related impairment in home, school, and social activities, and when the dimensions of tic severity were explored, impairment correlated most strongly with motor tic complexity. Results suggest that differentiating tic-related from non-tic-related impairment may be clinically beneficial and could lead to treatments that more effectively target problems experienced by children with PTDs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The Gilles de la Tourette syndrome (or Tourette's syndrome) has a prevalence of 1% of children with a wide range of severity and associated comorbidities. The last 20 years have seen advances in the understanding of the syndrome's complex genetics and underlying neurobiology. Investigation with imaging and neurophysiology techniques indicate it is a neurodevelopmental condition with dysfunction of basal ganglia-cortical interactions, which are now also being studied in animal models. There is also increasing evidence for treatments although it often remains difficult to manage. First-line options include neuroleptics, other drugs and specialised behavioural treatments. Deep brain stimulation is an evolving field, not yet fully established. This review focuses on the phenomenology of tics, how to assess and manage the syndrome, and uses examples of atypical cases to explore the characteristics and limits of its clinical spectrum., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Tourette syndrome (TS) is a childhood onset neurodevelopmental disorder characterised by motor and vocal tics and frequent associated comorbidities. The developmental trajectory of tic shows tic-onset in the age of 4-6, peak in the age of 10-12 and decline during adolescence, although only few and small longitudinal studies form the basis of this evidence. Recent studies suggest that comorbid obsessive-compulsive disorder (OCD), attention deficit-hyperactivity disorder (ADHD) and coexisting psychopathologies tend to persist and become more dominant in adolescence. This large prospective follow-up study want to examine the clinical course of TS: tic and comorbidities during adolescence, the prevalence of coexisting psychopathologies, the tic-related impairment, development in phenotype expression and find predictors for the expected course of TS. 
Method: This study is examining a large clinical cohort recruited at the Danish National Tourette Clinic during the period 2005-2007 and 2011-2013. At baseline, 314 participants aged 5-19 years were included and at follow-up 6 years later 227 participated, aged 11-26. All participants were uniformly clinically examined at basis and follow-up with a clinical interview and validated measurements to assess comorbidities. The Yale Global Tic Severity Scale was used to asses tic severity and tic-related impairment. At follow-up a cross-sectional diagnostic evaluation was made with the Development and Well-Being Assessment to assess coexisting psychopathologies.
 Results: A significant decline in tic and the most frequent comorbidities OCD and ADHD was found although some variation existed and some subclinical and partial remissions persisted. Tic-related impairment was not reflected in the tic-decline as expected but influenced by several parameters. The phenotype expression was found to be dynamic but overall changed toward TS without comorbidities. Several predictors were found to predict the clinical course of TS in adolescence and early adulthood. Childhood tics, OCD and ADHD severity were the strongest predictors for future symptoms of the respectively diagnoses. Comorbidities and coexisting psychopathologies were found in 63% at follow-up, whereas 37% had pure TS.
 Conclusion: The clinical course of TS during adolescence was confirmed, with solid evidence, with decline in tics, OCD and ADHD severity. We provide evidence of considerable coexisting psychopathologies requiring clinical support and partial remissions and subthreshold symptoms requiring monitoring and clinical guidance to assist the young adults in promoting a healthy transition into early adulthood. Furthermore we provide predictors for the clinical course of TS to be used in the preventive efforts, early intervention and allocation of resources improving quality of life for the children and their families.

Introduction: Autism spectrum disorders (ASD) are neurodevelopmental disorders that affect social communication and present stereotypic behaviours. Comorbidity associated to conduct disorders is frequent, starts in infancy and, in general, continues into adulthood. It is sometimes associated with aggressiveness, negativism, self-harm and breaking social norms. It causes a high degree of dysfunctionality in persons with ASD, their family, professionals and those around them, and is the main cause of pharmacological treatment, hospitalisation and special education. Factors related to the symptoms of ASD, comorbidity and social factors are associated with an increased risk of conduct disorders. In many cases it would be necessary to perform a detailed examination that includes a functional analysis and a combination of psychoeducational, social and pharmacological interventions., Aim: To review the precipitating factors, causes, evaluation and treatment of the conduct disorders associated with ASD., Development: The study outlines what is understood by conduct disorders in ASD, the different clinical and cognitive mechanisms associated with it, and the most effective strategies for intervention., Conclusions: Comorbid ASD with conduct disorders is frequent, begins in early infancy and continues throughout life. A detailed evaluation that includes a functional analysis of the behaviour to be eliminated and treatment with different psychological, social educational and pharmacological strategies are essential.

Background: The main goal of this study was to analyse and show clinical characteristics and psychiatric comorbidity in 38 participants aged between 10 and 17 with DSM-IV diagnoses of Trichotillomania (TTM) that we were treating at Children's Hospital Zagreb from 2008 to 2017., Subjects and Methods: We analyzed the data obtained from semi-structured interviews by the criteria of DSM-IV, Youth Self Report (YSR) (Achenbach & Rescorla 2001) and survey that we created., Results: From 38 participants 21 were girls. The activities during which the participants state that they mostly pull hairs are as follows: doing homework and learning, working on PC, in the toilet, watching TV etc. The most common sites on the body from which participants pulled hair were scalp and among nonscalp sites eyebrows and eyelashes. We found nail biting in more than a half of participants. In 22 participants one or more comorbid disorder has been found, of which ADHD (n=6) and tics (n=5) are most co-occurring disorders. The internalized and externalized problems were nearly evenly represented. Trichophagia was reported by two participants. The results indicate that more than two thirds of participants isolate themselves during hair pulling and half of them try to hide consequences. Median time from the first occurrence of the symptoms to the first visit to a child psychiatrist caused by TTM problem was 9 months (min 5; max 24) what we consider a very long period of time that increased the probability of complications., Conclusions: Knowledge about this disorder and cooperation among pediatric experts is extremely important for recognizing it at an early stage and starting the treatment especially considering habit-forming mechanism, the burden of an emotional distress and frequent comorbidity. Further research is needed.

While attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder have been shown to have major impacts on quality of life in individuals with Tourette syndrome, there is comparatively little data on how the presence of these comorbidities influence tic severity and treatment. 114 children (mean age 10.25 years) were extensively clinically phenotyped at a single specialty clinic. While there was no difference in Yale Global Tic Severity Scale (YGTSS) scores in children with versus without ADHD, children with obsessive compulsive behaviors had significantly higher YGTSS scores (p = 0.008). There was a significant correlation between YGTSS scores and age (r = 0.344, p < 0.001). Children with ADHD were more likely to be treated for their tics within the first two years of diagnosis (OR 3.51, p = 0.009). As tic severity does not appear to be greater in children with ADHD, this association may relate to greater overall psychosocial impairment in children with this comorbidity.

Objective: Both tics and enterovirus (EV) infections are common in children. The association between EV infections and tics has been seldom evaluated. The aim of this study was to evaluate the risk of diagnosed tics after EV infections in children., Methods: A nationwide retrospective cohort study was conducted to determine the risk of tics after EV infections by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged < 18 years with EV infection during 2000 to 2007 were enrolled. For comparison, non-EV-infected children were randomly selected and matched with EV-infected children at a 1:1 ratio according to sex, age, urbanization level, parental occupation, and the year of EV infection. All patients were followed up until the diagnosis of tics, death, loss to follow-up, withdrawal from the insurance system, or December 31, 2008., Results: A total of 282,321 EV-infected and 282,317 non-EV-infected children were included in this study. The mean age was 2.39 years in both cohorts. The overall incidences of tics were 9.12 and 6.21 per 10,000 person-years in the EV-infected and non-EV-infected cohorts, respectively. Children with EV infection were significantly associated with an increased risk of tics compared with those without EV infection (adjusted hazard ratio, 1.38; 95% confidence interval, 1.27-1.5). Multivariable analyses showed that boys, children living in urbanized areas, children whose parents had white-collar jobs, and children with allergic rhinitis or bronchial asthma exhibited a significantly increased risk of tics., Conclusion: This study revealed an increased risk of tics after EV infection in children.

The clinical surveillance and active management of Tourette syndrome (TS) and other primary chronic tic disorders cannot be limited to tics, as these patients manifest a spectrum of sensory-, behavioral-, cognitive-, and sleep-related problems that have a major impact on their functioning and quality of life, influencing enormously clinical decision making on a routine basis. The sensory phenomena of primary tic disorders consist of premonitory urges and heightened sensitivity to external somatosensory and interoceptive stimuli. Recent evidence suggests that raised interoceptive awareness may be related to the classical premonitory urges associated with tics. The burden of behavioral comorbidities is very important in determining the degree of disability of patients with primary tic disorders. Only 10%-15% of these patients presents exclusively with a tic disorder. Obsessive-compulsive disorder (OCD) are common in TS, and the clinical distinction between compulsions and complex tics may be difficult in some cases. "Tic-related OCD" represents a phenomenologically characteristic subtype of OCD, also associated with "just right" phenomena. Probably the presence of comorbid attention deficit/hyperactivity disorder is the main determinant of cognitive dysfunction in TS patients and influences heavily also the risk of developing disruptive behaviors. Mood and anxiety disorders, impulse control disorders, rage attacks, "impulsive" tic-like behaviors (e.g., nonobscene socially inappropriate behaviors, and self-injurious behaviors), and autism spectrum disorders complete the wide psychopathological spectrum of primary chronic tic disorders. Moreover, specific sleep abnormalities have been reported in TS patients, although more research is needed on this specific clinical problem. As in other areas of clinical neuroscience, a comprehensive approach to both motor and nonmotor aspects of this group of disorders will help personalizing treatment interventions and, ultimately, improve quality of care., (© 2017 Elsevier Inc. All rights reserved.)

Objectives: In a considerable minority of patients who suffer from Tourette syndrome (TS) the disorder persists into adulthood and is associated with severe symptoms and limited therapeutic options. Repetitive transcranial magnetic stimulation (rTMS) to the supplementary motor area (SMA) has shown promising therapeutic results. Deep rTMS is a novel technology that enables deeper non-invasive cortical stimulation. This open-label pilot study is the first to examine the possible role of deep rTMS as add-on treatment for intractable TS., Methods: Twelve patients were recruited in order to examine bilateral SMA inhibition via deep TMS using the HBDL coil, as a possible treatment for adult TS treatment-resistant patients. Two patients did not complete the 20-day study protocol., Results: There were no significant side effects. While tics did not improve among the group as a whole, the subgroup of six patients with combined TS and OCD (obsessive compulsive syndrome) showed significant improvement in tic severity (P = 0.037)., Conclusions: These findings support the safety of deep rTMS for treating TS. The results also highlight the importance of studying the different TS syndromes separately (e.g., with or without OCD comorbidity) when evaluating deep rTMS protocols for TS patients.

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.)

Little is known about risk factors for Tourette syndrome (TS) and chronic tic disorders (CT) but maternal psychological morbidity in pregnancy may be associated with TS/CT. We examined whether pre- and post-natal parental anxiety and/or depression are associated with risk of TS/CT in the Avon Longitudinal Study of Parents and Children. We compared self-reported anxiety and depression measures collected prospectively at four time points (18 and 32 weeks prenatally, and 8 weeks and 8 months post-natally) among parents of children who subsequently met criteria for TS/CT at 13 years of age as compared to other children from the cohort. We adjusted for various socioeconomic measures and tested both for time period-specific exposure and chronic exposure using multivariable logistic regression models. 122 children had TS/CT (50 TS, 72 CT) and 5968 children had no tics. In crude analyses, both pre- and post-natal maternal anxiety and depression, but only post-natal paternal depression at 8 months, showed associations with TS/CT. In the final, adjusted multivariable models, chronic maternal anxiety (odds ratio 2.17, 95% CI 1.23, 3.84, p = 0.007) and pre-natal maternal depression (odds ratio 1.86, 95% CI 1.02, 3.39, p = 0.04) showed associations with TS/CT though the latter was consistent with chance (p = 0.07) after adjustment for past maternal depression. We find associations between maternal psychological morbidity pre- and post-natally and risk of future TS/CT in offspring. These associations may reflect either shared genetic susceptibility or a pre-natal exposure. Further work is required to see if these findings can be replicated in larger datasets.