Pediatric TRTS might show an earlier age of onset age, longer duration of illness, lower IQ, higher premonitory urge, and higher comorbidities with ADHD-related symptoms and OCD-related symptoms. We need to pay more attention to the social communication deficits of TRTS.\citet{Araújo2022} examined the role of ADHD and OCD in tic severity during the COVID-19 pandemic in Brazilian and Portuguese patients with TS and found that approximately half of the patients experienced worsening of tic severity and they suggest patients with comorbidity might more susceptible to the effects of the pandemic.
Food difficulties, among others greater food responsiveness and emotional overeating, were shown to be more common in children with TS than previously reported \cite{Smith2022a}.
The experience of tic-related pain and use of pain management was assessed in an online survey answered by 188 adults with self-reported tics \cite{Taylor2022}. Tic-related pain was shown to have a significant physical and psychological impact and important to be addressed in the long-term managament of tic disorders. Similar study was conducted in Poland \cite{Ma_ek_2022}, but this time it was carried out in pediatric population. The authors included 40 children with GTS and 57 parents of children with GTS, as they wanted to collect information about perspective of children and parents on this topic. For assessment of tics the authors used the YGTSS, while pain severity, localization and coping stategies were assessed with the Pediatric Pain Questionnaire, and Pediatric Pain Coping Inventory which was administered both to children and parents. Pain was reported by 60% of children with GTS and 72% of parents confirmed that their children can suffer from pain. The most common localizations of pain were cervical region, throat, shoulder, ocular region and joints. Contrary to expected, no correlation has been found between tic severity and pain. Consistency between the declarations of children and their parents in coping with pain was observed.
A large Swedish cohort study with more than 13 million individuals and almost 7,800 individuals with TS or chronic tic disorders (CTD), it was found that persons with TS or CTD did have an increased risk of experiencing any violent assault and violent and nonviolent crime convictions \cite{Mataix-Cols2022}. The presence of comorbid ADHD and substance use disorders increased this risk.
Ricketts et al. \cite{Ricketts2022a} published an important article about sleep disorders and the use of sleep medication, nightime tics and pattern of sleep in patients with tics.In this study 125 adults with tics were included. The participants filled out an internet survey in which they rated sleep history, sleep chronotype as well as the severity of tics and psychiatric comorbidities. The most frequently reported sleep-related disorders in population of patients with tic disorders were bruxism, insomnia, tic-related difficulty falling asleep. Sleep problems correlated with impairment, obsessisive compulsive symptoms as well as emotional regulation problems. Interestingly enough, eveningness related to tic severity. Therefore, the authors concluded that interventions to advance chronotype may help with tic improvement. The same group of authors examined another aspect of sleep disorders in the group of patients with tics \cite{Ricketts2022b}. In this study 114 children with TS were included and the authors compared those who have sleep disorders (n=32) with those who have no problems with sleep (n=82). Children with TS and sleep disorder were from households with lower parental education and at the higher risk of poverty. They also were more frequently diagnosed with comorbidities such as OCD, ODD, ADHD and autism and were prescribed more frequently anti-tic medication. In line with these findings, children with TS and sleep disorder had more severe tics, tic-related impairment and more severe ADHD symptoms.
A case-control study including 271 children with tic disorder and 271 controls revealed that children with tic disorders had increased risks for sleep disturbances as measured with Children´s Sleep Habits Questionnaire \cite{Mi2022}. Sleep disturbances included among others bed time resistance, sleep onset delay, sleep anxiety, night waking, and daytime sleepiness. The presence of comorbid ADHD increased the risk for sleep disturbances.
\cite{Jiménez-Jiménez2022} published results of the register-based cohort study to estimate the prevalence of insomnia in patients with tics in Sweden. Individuals with tics had a prevalence of insomnia of 32.16% in comparison to 13.70% in the general population and this difference was statistically significant. Importantly, this association was indepentent from somatic disorders, familial factors or psychiatric comorbidities, although familial factors, neurodevelopmental comorbidities, and ADHD/ADHD medication may explain part of the association.
Nail biting (onychophagia) is very common in unselected children, but has also been included in descriptions of complex tics. A report from Taiwan examines prevalence of nail biting in over 2000 children, including 765 with a primary tic disorder, finding that nail biting is very common in TS (56.6%) and provisional tic disorder (27.4%)—much more common than in controls (15.0%)—and begins prior to onset of definite tics \cite{Hsueh2022}.
\cite{Cui_2022a} reported about emotional and behavioral profile of children with GTS in China and compare this profile with sex-matched health controls, ADHD, OCD and depression groups. To assess for behavioral and emotional problems in all groups the Child Behavior Checklist (CBCL) was implemented. No association between the eight factors of the CBCL and motor tics, vocal tics or tic severity assessed by the YGTSS was found. Nevertheless, there was a positive association between the impairment scale of the YGTSS and thought problems as well as rule-breaking behavior as assessed by the YGTSS. Contrary to expected, children with GTS showed similar profile of CBCL to the children with depression, but not ADHD and OCD.
\cite{Li2022} reported about children with refractory GTS and have found that pediatric refractory GTS is characterized by earlier age of onset, longer disease duration, lower IQ, higher prevalence of PU and higher prevalence of psychiatric comorbidities.
\cite{Baizabal-Carvallo2022c} published a study about self-injurious behaviors in GTS. The authors included 201 patients with GTS and 34 (16.9%) of them had comorbid SIB. Majority of patients experienced self-inflicted damage (11.4%), while only 3.5% of participants also experienced aggression towards the others and only 2% had what the authors denominated as tic-related SIB. In this study, the authors compared in detail the distribution of different tics in patient with SIB and without in univariable model and concluded that individuals with SIB are more inclined to have tics involving shoulder, trunk, arm, as well as dystonic tics; complex motor tics, copropraxia, complex phonic tics, higher number of phonic tics, coprolalia and OCD. In multivariable analysis SIB was found to be associated with complex motor tics, OCS and greater tic severity. Interestingly enough, patients with SIB have also been selected more frequently for the DBS procedure.
\cite{Vermilion2022}
Etiology
Genetics
Epigenetics
Environmental risk factors
In a Taiwan birth cohort of 309,376 singleton live births at term gestations showed an increased risk of tic disorders (6-52 weeks after birth) after exposure to particular matter with an aerodynamic diameter less than 2.5 μm \cite{Chang2022}.
\citet{Rönö2022} compared more than 5 million singletons born after the use of assisted reproductive technology (ART) with almost 5 million singletons born without the use of ART. There was not found a difference in risk of tic disorders between the groups.
In a nationwide cohort of 14,024 children and adolescents who were hospitalized with a bacterial infection with different pathogens, an increased risk of tic disorders was found when compared to controls without a bacterial infection \cite{Hsu2022}. Future studies are needed to replicate these findings.
Pathophysiology
Animal models
Pathological studies
Electrophysiology
An EEG study assessing inhibitory control of frontal lobe regions, which are important for motor inhibition in chronic tic disorders, was conducted using a stop signal task \cite{Zea2022}. Right superior frontal gyrus gamma event-related desynchronization (ERD) was elevated in patients with chronic tic disorder during stop preparation. Elevated right superior frontal gyrus gamma ERD correlated with decreased tic severity, suggesting that right superior frontal gyrus gamma ERD may reflect a mechanism of tic suppression. Using magnetoencephalography, error-related negativity, an event-related potential component and an index of performance monitoring processes during simple stimulus-response tasks, was examined for changes in the performance monitoring system in TS \cite{Metzlaff2022}. The results suggest that increased motor control induced by conflict between high target task performance and tic suppression in TS patients may influence early error-related processing, and that TS patients may initially tend to process all responses as error responses. In the future, it is envisioned that electroencephalography will be useful as a biomarker in TS and in understanding the pathophysiology of tics.
Electrophysiology has also been discussed as a biomarker for tic disorders. TMS was also discussed including reduced short-interval intracortical inhibition at rest, which suggests a correlation with motor tic severity, shortened cortical silent period duration, increased intracortical facilitation, and decreased motor evoked-potential amplitude \cite{Jannati2022}. Using EEG as a biomarker for comprehensive behavioral intervention (CBIT), a randomized controlled trial was conducted to determine whether EEG coherence during Go/NoGo tasks correlated with CBIT outcomes \cite{Morand-Beaulieu2022}. No association was found between EEG coherence during the Go/NoGo task and changes in tic severity, suggesting that brain processes in the inhibition of motor responses do not play any role in CBIT.