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Background: Current pharmacological treatments for Tourette Syndrome (TS), such as antipsychotic agents and α-2 agonists, are moderately effective in the treatment of tics, but have substantial side effects that limit their use. N-acetylcysteine (NAC) modulates glutamatergic systems, and has been used safely as an antioxidant agent with minimal side effects for decades. NAC has been increasingly studied for the treatment of other obsessive-compulsive spectrum disorders. We aim to examine the efficacy of NAC for the treatment of pediatric TS in a double-blind, placebo-controlled, add-on study. Methods: Thirty-one children and adolescents 8–17 years of age with TS were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of tics as measured by the Yale Global Tic Severity Scale (YGTSS), Total tic score. Secondary measures assessed comorbid obsessive-compulsive disorder (OCD), depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD). Linear mixed models in SAS were used to examine differences between NAC and placebo. Results: Of 31 randomized subjects, 14 were assigned to placebo (two females; 11.5 + 2.8 years) and 17 to active NAC (five females; 12.4 + 1.4 years) treatment. No significant difference between NAC and placebo was found in reducing tic severity or any secondary outcomes. Conclusions: We found no evidence for efficacy of NAC in treating tic symptoms. Our findings stand in contrast to studies suggesting benefits of NAC in the treatment of other obsessive-compulsive spectrum disorders in adults, including OCD and trichotillomania, but are similar to a recent placebo-controlled trial of pediatric trichotillomania that found no benefit of NAC.

[...]tics in these cases could be due to a concurrent primary tic disorder instead of secondary to JHD. Fine motor control impairment, irritability, tonic–clonic seizures, gait ataxia, and dystonia Chorea and cognitive impairment in father and 6 paternal family members across 3 generations 108 in patient; 47 in father; 52 in paternal uncle; 50 in paternal aunt Liu et al. 20146 10 years M Motor tics (limbs) Motor (limbs), no further details Gait disturbance, dysarthria, involuntary head wiggle, and foot dystonia None 82 in patient; no genetic testing for family Cui et al. 20177 9 years M Simple motor tics (blinking), complex motor tics (frowning), and simple phonic tics (throat clearing) Simple motor (blinking, jerking of head, shoulders, right upper limb, and lower limbs), complex motor (frowning), and simple phonic (throat clearing). Torticollis, ADHD, OCD, and night terrors None 49 in patient; <20 in mother and father Lesinskiene et al. 20208 11 years M Simple phonic tics (coughing and throat clearing) Simple phonic (coughing and throat clearing) Involuntary head and neck movements, irritable, social withdrawal, cognitive impairment, rigidity, dysarthria, depression, and psychosis HD in father and paternal family members across several generations 52 in patient; genetic testing not reported for family Lesinskiene et al. 20208 13 years M Simple phonic tics (throat clearning), involuntary chest and hip twitching during sleep, unsteady gait, rigidity, and dysarthria Simple phonic (throat clearing) Social withdrawal, cognitive impairment, hyperkinetic movements, impulsivity, and dysphagia HD in father and 1 paternal family member 69 in patient In contrast, our case had characteristics that support tics occurring secondary to JHD rather than a concurrent primary tic disorder.

Objective: The aim of this study was to conduct a pilot study testing whether single-dose, immediate-release dexmethylphenidate (dMPH) can facilitate tic suppression in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and Tourette's disorder (TD) or chronic tic disorders. The primary hypothesis is that dMPH will improve behaviorally reinforced tic suppression in a standard tic suppression paradigm (TSP). Methods: Ten children with ADHD and TD were given dMPH on one visit and no medication on another, using a random crossover design. On both days, following a baseline period, subjects were reinforced for suppressing tics using a standard TSP. Results: Thirteen subjects were enrolled; 10 subjects (mean age 12.7 ± 2.6; 90% male) completed all study procedures. Relative to the no-medication condition, tics were reduced when children were given a single dose of dMPH. Behavioral reinforcement of tic suppression resulted in lower rates of tics compared to baseline, but dMPH did not enhance this suppression. Conclusion: Preliminary results indicate replication of prior studies of behavioral tic suppression in youths with TD and without ADHD. In addition, our findings indicate tic reduction (and not tic exacerbation) with acute dMPH challenge in children and adolescents with ADHD and TD.

Correspondence to Dr Isobel Heyman, Great Ormond Street Hospital For Children NHS Foundation Trust, London WC1N 3JH, UK; i.heyman@ucl.ac.uk Explosion of tics Since the onset of the COVID-19 pandemic, paediatricians and child mental health practitioners have noticed an increase in tic symptoms in some children and adolescents already diagnosed with tic disorders.1 Interestingly, clinicians have also seen a marked increase in presentations of sudden and new onset of severe tics and ‘tic-like’ attacks. Functional symptoms as a part of an overall increase in mental health disorders during the COVID-19 pandemic The adverse impact of the COVID-19 pandemic on adult and child mental health is becoming increasingly evident.4 5 Rates of mental health problems in children and young people were 10.8% in the 2017 UK mental health survey. There is a need for collaboration between paediatric and mental health services. Once a positive diagnosis of functional tic-like attacks has been made, optimum management is likely to include integration of paediatric and mental healthcare7 and ensuring children and families understand the diagnosis and the usefulness of behavioural/psychological intervention.8 There are new data showing that referrals to child mental health services in September 2020 were 72% higher than in September 2019.9 It will be important that functional and mental health aspects are considered in the likely increase of physical presentations associated with long COVID in the coming year.

Background Tics are the hallmark of Tourette syndrome (TS) and chronic tic disorders (CTD). Although typically involving the face, especially at onset, tics may involve any muscle under voluntary control, including axial muscles of the neck (causing head movements), shoulders and trunk (thorax and abdomen). We aimed to characterize these tics and provide a clinical frame for their associations and complications. Materials and methods We reviewed video recordings and clinical history of 196 patients with TS or CTD according to DSM-5. Results Any axial tic was identified in 75% of patients. Tic distribution were head ( n  = 113, 57.6%), shoulder ( n  = 91, 46.4%), and trunk ( n  = 63, 32.2%). There were no differences in sex, age at onset or at evaluation between patients with and without axial tics. The most common axial tics by anatomical distribution were head turning, bilateral synchronous shoulder elevation and trunk jerks; however, tic phenomenology was quite variable. A greater severity of tics ( P  = 0.018) was associated with axial tics in the multivariate regression analysis. Head/neck tics associated with simple phonic tics ( P  = 0.002); whereas shoulder and trunk tics associated with complex motor tics ( P  < 0.05) in a bivariate analysis. Neck pain, breathing interference, sleep limitation and radiculopathy, secondary to axial tics were complications observed in a proportion of these cases. Conclusions Axial tics are commonly observed in patients with TS/CTD with variable phenomenology. They associate with greater tic severity, phonic tics and complex motor tics. They may result in neck pain, breathing interference, sleeping problems and cervical spine injuries.

Gilles de la Tourette Syndrome (GTS) is a developmental disorder. Empirical studies and an emerging cognitive framework on GTS suggest that GTS is a disorder of abnormally strong ‘perception-action binding’. Theoretical considerations imply that the effectiveness of long-established behavioral interventions might be related to a normalization of increased binding in GTS. This has not been tested yet. We examined the effect of a standardized Comprehensive Behavior Intervention for Tics (CBIT) in N = 21 adolescent GTS patients and N = 21 healthy controls on perception-action binding in an inhibitory control paradigm. Prior to CBIT, GTS patients showed compromised performance compared to controls, specifically when inhibitory control was triggered by uni-modal visual compared to bi-modal stimuli. After CBIT intervention, GTS patient’s performance was at the same level as healthy controls. This is supported by a Bayesian data analysis. CBIT specifically affected inhibitory control in a condition where reconfigurations of perception-action bindings are necessary to perform inhibitory control. A power of 95% was evident for these effects. CBIT reduces increased ‘binding’ between perception and action in GTS and thereby increases the ability to perform response inhibition. The results are the first to provide insights as to why CBIT is effective by relating elements of this intervention to overarching cognitive theoretical frameworks on perception-action bindings.

Objective: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a subtype of obsessive compulsive disorder (OCD) marked by an abrupt onset or exacerbation of neuropsychiatric symptoms. We aim to characterize the phenotypic presentation of youth with PANS. Methods: Forty-three youth (ages 4–14 years) meeting criteria for PANS were assessed using self-report and clinician-administered measures, medical record reviews, comprehensive clinical evaluation, and laboratory measures. Results: Youth with PANS presented with an early age of OCD onset (mean=7.84 years) and exhibited moderate to severe obsessive compulsive symptoms upon evaluation. All had comorbid anxiety and emotional lability, and scored well below normative means on all quality of life subscales. Youth with elevated streptococcal antibody titers trended toward having higher OCD severity, and presented more frequently with dilated pupils relative to youth without elevated titers. A cluster analysis of core PANS symptoms revealed three distinct symptom clusters that included core characteristic PANS symptoms, streptococcal-related symptoms, and cytokine-driven/physiological symptoms. Youth with PANS who had comorbid tics were more likely to exhibit a decline in school performance, visuomotor impairment, food restriction symptoms, and handwriting deterioration, and they reported lower quality of life relative to youth without tics. Conclusions: The sudden, acute onset of neuropsychiatric symptoms, high frequency of comorbidities (i.e., anxiety, behavioral regression, depression, and suicidality), and poor quality of life capture the PANS subgroup as suddenly and severely impaired youth. Identifying clinical characteristics of youth with PANS will allow clinicians to diagnose and treat this subtype of OCD with a more strategized and effective approach.

Background and objective: Antineuronal antibodies have been implicated in tic and obsessive compulsive disorders (OCD) associated with group A streptococcal infections. We investigated antineuronal autoantibody levels as well as antibody-mediated neuronal cell signaling activity, as previously reported for Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococci (PANDAS), to determine immunological profiles for a large cohort of children with tics and/or OCD. Methods: Study participants (n=311; ages 4–27 years, 66% male) were selected from a larger group of individuals with self-reported neuropsychiatric symptoms (n=742) and included only those with accurate knowledge of group A streptococcal infection status, except for four individuals in whom streptococcal infection status was unknown. Healthy control samples (n=16; ages 5–14 years, 81% male), came from the National Institute of Mental Health and Yale University. In addition to serum donations, participants and/or legal guardians provided neuropsychiatric and related medical histories of symptoms that had lasted >1 year. Antineuronal immunoglobulin G (IgG) titers were measured by standard enzyme-linked immunosorbent assay (ELISA) and compared with mean titers of normal age-matched sera against lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) activity in a human neuronal cell line (SK-N-SH) was tested in serum. Results: Of 311 individuals, 222 (71%) had evidence of group A streptococcal infection, which was associated with tics and/or OCD status (p=0.0087). Sera from individuals with tics and/or OCD (n=261) had evidence of elevated serum IgG antibodies against human D1R (p<0.0001) and lysoganglioside (p=0.0001), and higher serum activation of CaMKII activity (p<0.0001) in a human neuronal cell line compared with healthy controls (n=16). Furthermore, patients with tics and OCD had significantly increased activation of CaMKII activity compared with patients with only tics or only OCD (p<0.033 for each). Conclusion: Our study suggested a significant correlation of streptococcal-associated tics and OCD with elevated anti-D1R and antilysoganglioside antineuronal antibodies in serum concomitant with higher activation of CaMKII in human neuronal cells. Youth and young adults with chronic tics and OCD may have underlying infectious/immunologic etiology.

The pain, which developed alongside the spasms, was characterised by frequent episodes of excruciating, lancinating pain—rated by the patient as very severe using a visual analogue pain scale—along the ophthalmic and maxillary branches of the trigeminal nerve. The common source of our patient's two diagnoses shows that surgical microvascular decompression can be an effective and long-lasting treatment for either conditions—presenting alone or together—where medical treatments have failed. Acknowledgments This work was made possible by a grant from the National Institutes of Health (NIH NCATS KL2 TR002539).

In children, exacerbations of tics and obsessive symptoms may occur after infection with group A β-haemolytic streptococci. If post-streptococcal autoimmunity is the cause of the exacerbations, then children might respond to immunomodulatory treatments such as plasma exchange or intravenous immunoglobulin (IVIG). We studied whether plasma exchange or IVIG would be better than placebo (sham IVIG) in reducing severity of neuropsychiatric symptoms. Children with severe, infection-triggered exacerbations of obsessive-compulsive disorder (OCD) or tic disorders, including Tourette syndrome, were randomly assigned treatment with plasma exchange (five single-volume exchanges over 2 weeks), IVIG (1 g/kg daily on 2 consecutive days), or placebo (saline solution given in the same manner as IVIG). Symptom severity was rated at baseline, and at 1 month and 12 months after treatment by use of standard assessment scales for OCD, tics, anxiety, depression, and global function. 30 children entered the study and 29 completed the trial. Ten received plasma exchange, nine IVIG, and ten placebo. At 1 month, the IVIG and plasma-exchange groups showed striking improvements in obsessive-compulsive symptoms (mean improvement on children's Yale-Brown obsessive compulsive scale score of 12 [45%] and 13 [58%], respectively), anxiety (2·1 [31%] and 3·0 [47%] improvement on National Institute of Mental Health anxiety scale), and overall functioning (2·9 [33%] and 2·8 [35%] improvement on National Institute of Mental Health global scale). Tic symptoms were also significantly improved by plasma exchange (mean change on Tourette syndrome unified rating scale of 49%). Treatment gains were maintained at 1 year, with 14 (82%) of 17 children “much” or “very much” improved over baseline (seven of eight for plasma exchange, seven of nine for IVIG). Plasma exchange and IVIG were both effective in lessening of symptom severity for children with infection-triggered OCD and tic disorders. Further studies are needed to determine the active mechanism of these interventions, and to determine which children with OCD and tic disorders will benefit from immunomodulatory therapies.