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.

Prenatal and postnatal exposure to PM2 .5 and the risk of tic disorders.

BACKGROUND: Tic disorders are common neurodevelopmental disorders during childhood. Whether prenatal and postnatal exposure to particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5 ) plays a role in the development of tic disorders remains unexplored. OBJECTIVES: To investigate the association of exposure between PM2.5 during the pregnancy and infancy periods and the risk of tic disorders. METHODS: This birth cohort study recruited singleton live births at term gestations in central Taiwan from the Taiwan Maternal and Child Health Database between 2004 and 2012 and followed up to the end of 2017. New cases of tic disorders were defined using the ICD-9-CM (307.2) and ICD-10-CM (F95), which include all tic spectrum disorders. We assigned daily PM2.5 concentrations derived from a satellite-based model to individuals based on maternal residential addresses at delivery. We fit Cox proportional hazard model and distributed lag non-linear model to estimate the associations between PM2.5 and tic disorders, with hazard ratio (HR) with 95% confidence interval (CI) as the effect measure. RESULTS: Of the 309,376 singleton live births at term gestations, we identified 5902 (1.9%) tic disorder cases. The HR of tic disorders was positively associated with a 10 µg/m3 increase in PM2.5 : during pregnancy HR 1.09, 95% CI 1.04, 1.15 and during infancy HR 1.12, 95% CI 1.06, 1.18. The vulnerable time window for infants with increased risk of tic disorders was 6-52 weeks after birth. We observed a nonlinear relationship between PM2.5 and the risk of tic disorders, with exposure to PM2.5 between 16 and 64 µg/m3 being associated with the risk of tic disorders. The association was restricted to Tourette's disorder group. Infant sex did not modify these associations. CONCLUSIONS: Infants delivered at term and exposed to PM2.5 are associated with an increased risk of tic disorders (6-52 weeks). Further studies are needed to confirm these associations.

Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder and Tic Disorder: A Quick Review.

Repetitive transcranial megnetic stimulation (rTMS) has been widely used in patients with psychiatric disorders. Previous studies revealed good efficacy of rTMS for patients with obsession-compulsive disorder (OCD) and Tic disorder (TD). OCD and TD are closely related and considered to etiologically overlap. Patients with the co-occurrence of OCD and TD are often identified. Therefore, we conducted a quick review of rTMS for the treatment of these two diseases to compare the similarities and differences of rTMS for OCD and TD, which might provide an indication for the treatment of the co-occurrence of OCD and TD. We searched articles published in PubMed, Wanfang, and Web of Science from January 2001 to January 2022. Both inclusion criteria and exclusion criteria were developed to identify the relevant included studies. Data on the frequency, target area, sample size, and number of males, especially the rTMS treatment procedure or parameters, were extracted in the included studies. We included 26 studies on OCD and 12 studies on TD in this quick review. A total of 996 participants were included. Based on the review of the included studies, lowfrequency rTMS might be used more than high-frequency rTMS, and the supplementary motor area (SMA) might show better efficacy than the dorsolateral prefrontal cortex (DLPFC) in OCD. For patients with TD, low-frequency rTMS located in the SMA might show good efficacy both in OCD and TD. Our quick review elaborated the treatment efficacy of rTMS for both patients with OCD and those with TD. It seems that the SMA is an important target choice for both OCD and TD patients. Low-frequency rTMS might be used more than high-frequency rTMS in both OCD and TD patients. In future studies, we should explore more about the efficacy of rTMS for patients with co-occurring OCD and TD, especially for the efficacy of targeted SMA with low frequency.

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.

Cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome.

INTRODUCTION: Gilles de la Tourette syndrome (GTS) is a childhood onset disorder characterised by the presence of motor and vocal tics. The guidelines of both the American Academy of Neurology (AAN) as well as the European Society for the Study of Tourette Syndrome (ESSTS) recommend behavioural therapy and pharmacotherapy, mainly with antipsychotics, as first line treatments for tics. In spite of these well-established therapeutic approaches, a significant number of patients are dissatisfied because of insufficient tic reduction or intolerable side effects. Previous studies have suggested that cannabis-based medicine (CBM) might be an alternative treatment in these patients. MATERIAL AND METHODS: Two reviewers (KS, NS) searched the electronic database of PubMed on 1 July, 2021 for relevant studies using the search terms: ('Tourette syndrome' [MeSH Terms] OR 'Gilles de la Tourette syndrome' [MeSH Terms] OR 'tic disorders' [MeSH Terms] OR 'tics' [MeSH Terms] OR 'tic disorders'[Title/Abstract]) AND ('cannabis-based medicine' [Title/Abstract] OR 'cannabis' [Title/Abstract] OR 'dronabinol' [Title/Abstract] OR 'nabiximols' [Title/Abstract] OR 'tetrahydrocannabinol' [Title/Abstract] OR 'THC' [Title/Abstract] OR 'cannabidiol' [Title/Abstract], limit: 'humans'. These studies were further reviewed for additional relevant citations. The titles and abstracts of the studies obtained through this search were examined by two reviewers (KS, NS) in order to determine article inclusion. Discrepancies were addressed by the reviewers through discussion and eventually conversation with the senior reviewer (KMV). RESULTS: Although the amount of evidence supporting the use of CBM in GTS is growing, the majority of studies are still limited to case reports, case series, and open uncontrolled studies. To date, only two small randomised controlled trials (RCTs) using tetrahydrocannabinol (THC, dronabinol) have been published demonstrating the safety and efficacy of this intervention in the treatment of tics in patients with GTS. On the other hand, another RCT with Lu AG06466 (formerly known as ABX-1431), a modulator of endocannabinoid neurotransmission, has failed to prove effective in the therapy of GTS. Accordingly, under the guidelines of both the ESSTS and the AAN, treatment with CBM is categorised as an experimental intervention that should be applied to patients who are otherwise treatment-resistant. CONCLUSIONS: Increasing evidence suggests that CBM is efficacious in the treatment of tics and psychiatric comorbidities in patients with GTS. The results of ongoing larger RCTs, such as CANNA-TICS (ClinicalTrials.gov Identifier: NCT03087201), will further clarify the role of CBM in the treatment of patients with GTS.

Reversible posterior leukoencephalopathy syndrome due to adrenal pheochromocytoma: A case report and literature review.

RATIONALE: Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare neuropathic syndrome with typical clinical and radiological features. There are large amounts of risk factors resulting in RPLS, those including hypertension, eclampsia, neoplasia treatment, renal failure, systemic infections, chemotherapy, and immunosuppressive therapy after organ transplantation. PATIENT CONCERNS: A 27-year-old male patient was admitted for a 2-week history of paroxysmal tic of limbs along with consciousness disorder. Blood pressure elevation was discovered for the first time on admission, and the highest record was 210/150 mmHg during hospitalization. Neurological examinations were positive among mental state, speech, reaction and pathological reflex. The computed tomography scan of the abdomen demonstrated a mass derived from right adrenal gland. The magnetic resonance imaging of the brain showed reversible lesions in the centrum ovale, paraventricular, area and corpus callosum. DIAGNOSES: After control of blood pressure and rationally preoperative preparation, the mass was radically resected and verified to be pheochromocytoma by postoperative pathologic findings. He was diagnosed as having RPLS due to adrenal pheochromocytoma. INTERVENTIONS: The right adrenal gland mass was completely removed after 2 weeks of α-blockers and ß-blockers to treat hypertension. OUTCOMES: One week after surgery, the cerebral lesions of RPLS gradually faded and the blood pressure was easy to control well. LESSONS: A few case reports of RPLS related to pheochromocytomas had been documented in the literature. Therefore, we believe that pheochromocytomas may be a potential risk factor of RPLS. If patients receive timely diagnosis and treatment, it can often lead to a favorable prognosis.

New-onset tic disorder following circumscribed brain injury.

Adult-onset tics represent either a secondary tic disorder ("tourettism") or a late presentation of childhood tics, which may have been previously unrecognised. Head trauma has been recognised as an infrequent cause of adult-onset tic disorder, which exhibits variable temporal relationship to the inciting injury and response to therapy. We present a patient who presented with late-onset tics seven years after a circumscribed brain injury, responding well to antidopaminergic treatment. A review of all the previously reported cases of post-traumatic tic disorder is provided. Our patient is unusual in that the injury presumed to be responsible for the development of tics was of a very focal nature, akin to previously described tic disorder following vascular insults. We discuss the rare occurrence of tourettism after such focal brain lesions and analyse the insights this provides into the anatomical substrates underlying tic disorders.

Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding?

BACKGROUND: Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences. METHODS: A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models. RESULTS: PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys. CONCLUSIONS: Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.

Association between allergic conjunctivitis and provisional tic disorder in children.

BACKGROUND: Allergic diseases are associated with a higher risk of Tourette's syndrome (TS). Provisional tic disorder (PTD) and eye blinking are often reported as the initial symptoms both in TS and in allergic conjunctivitis (AC). OBJECTIVE: To investigate the association between AC and PTD in children of 4-10 years of age in southwest China. METHODS: This case-control study was carried out at the Children's Hospital of Chongqing Medical University between January 2016 and June 2017. Age- and gender-matched children without PTD were included as the control group. Intraocular pressure was measured by non-contact tonometry, tear film break-up time by slit-lamp examination, and allergens by skin prick test (SPT). Multivariable logistic regression analysis was applied to adjust for the simultaneous effects of AC, dry eye, and allergic history in children with PTD. RESULTS: The frequency of AC was higher in the PTD group (74.3%, 52/70) than in the control group (17.1%, 12/70) (P < 0.001). The frequencies of positive SPT were found to be higher in the PTD group (80.0%, 56/70) than in the control group (20.0%, 14/70). AC, dry eye, and history of allergic rhinitis were significantly associated with PTD. CONCLUSION: The frequencies of AC are high in children with PTD. AC and dry eye may be both associated with PTD in children.

Tic Disorders and PANDAS.

Tics are the most common movement disorder in childhood and are a frequent reason for referral to child neurology clinics. The purpose of this review is to examine the phenomenology of tics, discuss what is known regarding their genetic and pathophysiological causes and to evaluate current treatment options. The evidence for the evaluation and treatment of the controversial diagnosis of pediatric autoimmune neuropsychiatric disorders associated with group A streptococci (PANDAS) will also be reviewed. With improved understanding of tic disorders, their etiology and response to current treatment options, we may be able to more effectively diagnose them and identify novel treatment strategies.

Antibiotics for PANDAS? Limited Evidence: Review and Putative Mechanisms of Action.

OBJECTIVE: Antibiotics have been used extensively by clinicians to treat patients with PANDAS or PANS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and pediatric acute-onset neuropsychiatric syndrome, respectively). This review examines the best-quality evidence supporting the practice-based use of antibiotics in these psychiatric conditions. DATA SOURCES: PubMed was searched for English-language articles published between January 1994 and July 2017 using the search terms [PANDAS OR PANS OR new-onset pediatric OCD] AND [antibiotics OR macrolides OR beta-lactams]. STUDY SELECTION: Randomized clinical trials, observational studies, and case reports concerning antibiotic use in PANDAS/PANS were reviewed. Four publications were included in the quantitative synthesis. DATA EXTRACTION: The evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method. RESULTS: Although the single studies conveyed no statistically significant results, there is some evidence for efficacy of antibiotic therapy in reducing neuropsychiatric symptoms in the PANDAS/PANS population. CONCLUSIONS: Whereas the use of eradicating antibiotic therapy during active infections in PANDAS/PANS is well established, there is still a need for studies that improve the quality of evidence supporting use of antibiotics in this population independent of ongoing infections. Studies that compare antibiotics with other therapies, as well as studies that assess safety and efficacy of long-term use of antibiotic therapy in PANDAS/PANS, are still lacking. However, the available research supports evidence of a subgroup in the pediatric OCD population that is sensitive to antibiotic treatment and immunomodulatory therapy, independent of ongoing infectious conditions. Thus, more studies are warranted in the overall OCD spectrum.

Chronic tic disorders in children with ADHD.

OBJECTIVE: To examine in a community-based cohort: (1) the prevalence of chronic tic disorder (CTD) in children with attention-deficit/hyperactivity disorder (ADHD) compared with non-ADHD controls at ages 7 and 10; and (2) the additional psychiatric and functional burden of CTD in children with ADHD. METHODS: Children aged 6-8 years with ADHD (n=179) and controls (n=212) were recruited through 43 Victorian schools using parent and teacher screening surveys (Conners 3 ADHD Index), followed by case confirmation (Diagnostic Interview Schedule for Children-IV (DISC-IV)). CTD was identified using the DISC-IV categories chronic motor tic disorder, chronic vocal tic disorder or Tourette syndrome at baseline and 36-month follow-up. Internalising and externalising disorders, social functioning, academic performance and quality of life were also measured. Tests of proportions and independent t-tests were used to compare the ADHD+CTD group with sex-matched ADHD alone children. RESULTS: Compared with controls, children with ADHD were 4.1 (95% CI 1.1 to 14.1) times more likely to have CTD at age 7, and 5.9 (95% CI 1.6 to 17.9) times more likely at age 10. Children with ADHD+CTD experienced higher rates of internalising disorders and peer problems, and poorer quality of life than those with ADHD alone. CONCLUSIONS: CTD prevalence is higher in children with ADHD compared with controls, and confers substantial additional psychiatric and functional burden. Clinicians need to consider CTD in both the initial assessment and ongoing management of children with ADHD, and address both the symptoms and the associated impairments.

Tourette disorder and other tic disorders.

Tourette disorder is a developmental neuropsychiatric condition characterized by vocal and motor tics that can range in severity from mild to disabling. It represents one end of a spectrum of tic disorders and is estimated to affect 0.5-0.7% of the population. Accumulated evidence supports a substantial genetic contribution to disease risk, but the identification of genetic variants that confer risk has been challenging. Positive findings in candidate gene association studies have not replicated, and genomewide association studies have not generated signals of genomewide significance, in large part because of inadequate sample sizes. Rare mutations in several genes have been identified, but their causality is difficult to establish. As in other complex neuropsychiatric disorders, it is likely that Tourette disorder risk involves a combination of common, low-effect and rare, larger-effect variants in multiple genes acting together with environmental factors. With the ongoing collection of larger patient cohorts and the emergence of affordable high-throughput genomewide sequencing, progress is expected to accelerate in coming years.

[Serum levels of 25-hydroxyvitamin D in children with tic disorders].

OBJECTIVE: To examine serum 25-hydroxyvitamin D levels in children with tic disorders (TD) and to explore the relationship between vitamin D level and TD. METHODS: One hundred and thirty-two children who were diagnosed with TD between November 2016 and May 2017 were enrolled as the TD group, including 8 cases of Tourette syndrome, 32 cases of chronic TD, and 92 cases of transient TD. One hundred and forty-four healthy children served as the control group. Peripheral venous blood samples were collected from each child. Serum levels of 25-hydroxyvitamin D were measured using HPLC-MS/MS. The categories of vitamin D status based on serum 25-hydroxyvitamin D level included: normal (>30 ng/mL), insufficiency (10-30 ng/mL) and deficiency (<10 ng/mL). RESULTS: Mean serum level of 25-hydroxyvitamin D in the TD group was significantly lower than that in the control group (P<0.01). The rate of vitamin D insufficiency or deficiency in the TD group was significantly higher than in the control group (P<0.01). Mean serum level of 25-hydroxyvitamin D in the transient tic group was higher than in the TS group (P<0.05). CONCLUSIONS: Vitamin D insufficiency or deficiency might be associated with the development of TD, and the level of serum 25-hydroxyvitamin D might be related to the classification of TD.

Association of Streptococcal Throat Infection With Mental Disorders: Testing Key Aspects of the PANDAS Hypothesis in a Nationwide Study.

Importance: Streptococcal infection has been linked with the development of obsessive-compulsive disorder (OCD) and tic disorders, a concept termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). However, previous studies of this association have been small, and the results have been conflicting. Objective: To investigate the risk of mental disorders, specifically OCD and tic disorders, after a streptococcal throat infection. Design, Setting, and Participants: A population-based cohort study was conducted using data from the nationwide Danish registers from January 1, 1996, to December 31, 2013, with up to 17 years of follow-up. The Danish National Health Service Register provided information on individuals with the registration of a streptococcal test. Data analysis was conducted from January 1, 2016, to February 28, 2017. Main Outcomes and Measures: Individuals were followed up in the nationwide Psychiatric Central Register for a diagnosis of any mental disorder, OCD, or tic disorders. Incidence rate ratios (IRRs) were calculated by Poisson regression analysis. Results: Of the 1 067 743 children (<18 years of age) included in the study (519 821 girls and 547 922 boys), 638 265 received a streptococcal test, 349 982 of whom had positive test results at least once. Individuals with a positive streptococcal test result had an increased risk of any mental disorder (n = 15 408; IRR, 1.18; 95% CI, 1.15-1.21; P < .001), particularly of OCD (n = 556; IRR, 1.51; 95% CI, 1.28-1.77; P < .001) and tic disorders (n = 993; IRR, 1.35; 95% CI, 1.21-1.50; P < .001), compared with individuals without a streptococcal test. Furthermore, the risk of any mental disorder and OCD was more elevated after a streptococcal throat infection than after a nonstreptococcal infection. Nonetheless, individuals with a nonstreptococcal throat infection also had an increased risk of any mental disorder (n = 11 315; IRR, 1.08; 95% CI, 1.06-1.11; P < .001), OCD (n = 316; IRR, 1.28; 95% CI, 1.07-1.53; P = .006), and tic disorders (n = 662; IRR, 1.25; 95% CI, 1.12-1.41; P < .001). Conclusions and Relevance: This large-scale study investigating key aspects of the PANDAS hypothesis found that individuals with a streptococcal throat infection had elevated risks of mental disorders, particularly OCD and tic disorders. However, nonstreptococcal throat infection was also associated with increased risks, although less than streptococcal infections for OCD and any mental disorder, which could also support important elements of the diagnostic concept of pediatric acute-onset neuropsychiatric syndrome.

Prenatal Maternal Smoking and Increased Risk for Tourette Syndrome and Chronic Tic Disorders.

OBJECTIVE: We assessed the role of prenatal maternal smoking in risk for Tourette syndrome and chronic tic disorder (TS/CT) and pediatric-onset obsessive-compulsive disorder (OCD). METHOD: In an analysis of 73,073 singleton pregnancies from the Danish National Birth Cohort, we calculated incidence rates (IR) per 1,000 person-year for TS/CT and OCD. We then determined crude and adjusted hazard ratios and 95% CIs associated with prenatal maternal smoking, considering smoking as a dichotomous (yes/no) variable or a stratified variable (no smoking, light smoking, and heavy smoking [≥10 cigarettes/day]). Additional analyses examined the effect of maternal smoking on risk for TS/CT with other comorbid psychiatric conditions. RESULTS: In final adjusted analyses, heavy smoking was associated with a 66% increased risk for TS/CT (adjusted hazard ratio = 1.66, 95% CI = 1.17-2.35). In addition, heavy smoking was associated with a 2-fold increased risk for TS/CT with comorbid attention-deficit/hyperactivity disorder (ADHD), and both light and heavy smoking were associated with a more than 2-fold increased risk for TS/CT with any non-ADHD psychiatric comorbidity. Our parallel analyses of pediatric-onset OCD were likely underpowered but showed similar relationships. CONCLUSION: Prenatal maternal smoking was associated with increased risk for TS/CT as well as TS/CT with comorbid psychiatric conditions, even after adjustment for several important variables, including maternal psychiatric history, socioeconomic status, and partner smoking. Our findings point to a pathway linking prenatal tobacco exposure and altered brain development to TS/CT.