Copyright © 2023-2024, the authors. 

Introduction

This article is meant to disseminate scientific progress on Tourette Syndrome (TS) that appeared in the year 2023, summarizing research reports the authors judged important or interesting. 

Methods

We searched PubMed using the search strategy ("Tic Disorders"[MeSH] OR Tourette) NOT ((Tourette[AU] OR Tourette[COIS]) NOT ("Tic Disorders"[MeSH] OR Tourette [tiab])) AND 2023[PDAT] NOT 1800:2022[PDAT]. On 16 Jan 2024 this search returned 278 citations. A search of PubMed Central for "tic disorders"[mesh] OR tourette*[ti] OR tourette*[ab] OR Tourette*[kwd] OR tourettism[tw] AND 2023[dp] NOT 1800:2022[dp] on the same date returned 218 citations, many overlapping. All these citations are available at this link. Colleagues also recommended articles, and we attended selected medical conferences. We selected material for this review subjectively, guided by our judgment of possible future impact on the field.

Results

Phenomenology and natural history

Definition and phenomenology

Baizabal-Carvallo and colleagues examined 156 patients with TS and 38 patients with secondary tic disorders (of whom some had functional tics) by evaluation of video-recordings and assessment of the clinical history \citep{Baizabal-Carvallo2023c}. Compared to patients with secondary tic disorders, patients with TS were more likely to have earlier onset of tics, greater complexity and severity of tics, and tics affecting primarily the head and neck area. Furthermore, patients with TS were more likely to be male. They suggest considering another tic disorder than TS if these characteristics are absent.  The same group examined differences between oromandibular tics and tardive dyskinesia.  Forty-one patients were identified with oromandibular tics and these were compared with 35 patients with classic tardive dyskinesia. The latter group of patients was found to have more frequent continuous tongue, oromandibular and masticatory movements \citep{Baizabal-Carvallo2023d}. According to another study by Baizabal-Carvallo and colleagues, blocking tics occur in 6% of patients (12/201). The most common type of blocking phenomenon was arrest in speech, followed by motor blocking phenomena. There was a correlation between blocking tics and the presence of dystonic tics and the number of phonic tics \citep{Baizabal-Carvallo2023b}.   
Several studies have examined gender differences in children and adolescents with tics \citep{Larsh2023,Larsh2024,Nilles2023}. Gender differences in tic- and non-tic-related impairment were examined in 132 adolescents aged 13-17 years \citep{Larsh2023}. Tic- and non-tic-related impairment were higher in adolescent girls then in boys, and in girls parent-reported non-tic-related impairment was correlated with symptoms of OCD. In a second study, sex differences in tic severity by retrospectively reviewing Yale Global Tic Severity Scale (YGTSS) measures in 373 adolescents (13-17 years) before coronavirus disease 2019 (COVID-19) pandemic and during the pandemic \citep{Larsh2024}. There was no difference in tic severity between the sexes before the pandemic, but during the pandemic where girls had more severe tics than boys. Nilles and colleagues assessed the influence of sex and age on the phenomenology of tics by examining 203 children and adolescents using the YGTSS \citep{Nilles2023}. Both were found to affect tics; females had higher frequency and intensity of motor tics than males and this was associated with a greater impairment. Age was positively correlated with total tic severity score.

Assessment and quantification of tics

The Motor Tic, Obsession and Compulsion and Vocal Tic Evaluation Survey (MOVES) is an established assessment for tics. Lewin and colleagues evaluated whether only subset of questions can be used as a short screening tool. Both version of the scale demonstrated good sensitivity and specificity was acceptable in comparison to expert assessment \citep{Lewin2023}  .   
Two machine learning algorithms for automatic tic detection were evaluated in 64 videos on 35 patients with TS \citep{37166278}. Tic detection F1 scores (79.5-82.0%) showed that the algorithms are feasible and reliable and might become useful in the assessment and differential diagnosis of tics.
Riechmann and colleagues revised the Rush Video-Based Tic Rating Scale in order to improve the use in research settings \citep{Riechmann2023}. In total, 102 videos of patients with TS or persistent motor tic disorder were included. Reducing the video time from 10 minutes to 5 minutes did not lead to significant changes in the assessment of tic frequencies. Furthermore, proposed adaptions in anchor values for tic frequency improved correlation with the YGTSS Score, and psychometric properties were acceptable. 

Prognosis and natural history

In a nationwide cohort study in Sweden, 3761 individuals with tic disorders in childhood were included in order to examine the prevalence and risk factors for the persistence of tic disorders  into adult life \citep{37246931}. In total, 20% of children with tic disorder received a chronic tic disorder diagnosis in childhood. The strongest risk factors for tic persistence were psychiatric comorbidity in childhood and family history of psychiatric disorders.

Sensory phenomena and premonitory urge

In this online study, the authors investigated the nature of  non-just-right experiences (NJRE) that have been previously linked to premonitory urges (PU) as well as to obsessive-compulsive disorders (OCD) \citep{Brandt2023}. One hundred eleven patients with TS completed different self-assessments for tics, PU and comorbid OCD/obsessive compulsive behaviors (OCB). NJRE were more related to the OCD spectrum than to PU or tics. The same group \citep{Brandt2023a}  examined clinical characteristics of PU in a large cohort of patients with chronic tic disorders (n=291). PU varied with tic severity. In the vast majority of patients, tics were followed by relief of the urge. ADHD, depression, female gender, and older age were identified as factors associated with the presence of PU. By contrast, OCD and younger age were associated with higher urge intensity.   
Larsh and colleagues used a combined approach to determine whether cortical properties such as excitability (CE) as well as cortical inhibition (LICI) correlate with PU and tics. In line with previous studies, PU intensity correlated with tic severity, and higher urge severity correlated with lower CE and LICI \citep{Larsh2023a}
Li and colleagues published results of a systematic review and meta-analysis investigating relationship between urge severity and neuronal correlates \citep{Li2023}. Altogether, 22 studies were identified with a total of 1236 patients. A meta-regression demonstrated that age and tic severity were related to PU severity. From a neuroanatomical perspective, PU was related to the following regions of the brain:  insula, prefrontal cortex, anterior cingulate cortex, and supplementary motor area.  
 A study from Japan explored pre-movement gating (attenuation) using somatosensory evoked potentials (SEPs) \citep{Kimura2023}. The authors found that  sensorimotor processing was preserved for simple tics but impaired for complex tics in a group of individuals after middle adolescence.

Transient effects of environment on tic severity

A fascinating study from Israel examined the timing of tics moment to moment while children with tic disorders watched a movie and played a video game \citep{37946628}. Tics did not occur randomly over time but rather were more or less common across participants during specific moments of the movie clip and when reward was expected in the video game. One interesting hypothesis presented for future study was that "the portrayal of motor actions in movies elicits" an urge to tic. Similarly, one would be very interested in whether movie or game conditions eliciting higher tic rates correspond to greater release of striatal dopamine in people with and without tics \citep{9607763}.
A group from Italy explored the impact of SARS-COV-2 infection in children and adolescents with TS \citep{Prato_2023}. Participants who had COVID-19 infection experienced both short-lasting as well as long-lasting symptoms ("long COVID"). Of note, 35% of patients experienced worsening of tics and/or of psychiatric comorbidities. The impact of the COVID-19 pandemic on tics was also investigated by Hall and colleagues \citep{Hall2023}. The authors compared YGTSS scores before and during the pandemic in children and young people (N = 112). No significant differences were found between the two assessments.
In a population-based study, Jack and colleagues reported that the incidence of tics in children and young people increased across all age and sex groups during the COVID-19 pandemic, especially in teenage girls \citep{Jack_2023}. However, it is plausible to speculate that many of the patients diagnosed with tics in fact had FTLB, since it is well known that the incidence of FTLB dramatically increased during the pandemic and many of these patients were misdiagnosed with TS.

Functional tic-like behaviors

Various authors have identified differences in the frequency or character of premonitory phenomena (PU) as a potential feature that can discriminate functional tic-like behaviors (FTLB) from primary tic disorders \citep{36362696,Martino2023}. The frequency of PU in those prior reports differed to a clinically important degree from the frequency in typical tic patients at a similar disease duration \citep{37224324}. However, prospectively comparing 83 patients with typical tics and 40 with FTLB from the Calgary tic registry, Szejko and colleagues found no significant differences in premonitory urge severity (PUTS scale total score) nor in any of the individual PUTS items \citep{Szejko_2023}. The authors noted that their results are supported by other reasonably large case series \citep{36203825,34824091}, and provide a brief but compelling discussion of potential implications.
Clinical differences between functional tics and neurodevelopmental tics were confirmed in a study by Cavanna and colleagues \citep{Cavanna2023}. In this study, 105 consecutive patients who had developed functional tics in the period from April 2020 to March 2023 were examined using a neuropsychiatric assessment. Besides the (sub)acute onset and high frequency of complex movements and vocalizations, it was shown that 23% of patients had a pre-existing tic disorder, 70% had comorbid anxiety, 40% had a comorbid affective disorder, and 41% had at least one other functional neurological disorder. The same group directly compared the clinical features of patients who developed functional tics during the COVID-19 pandemic (N = 83) to patients with TS matched for age and gender (N = 83) \citep{37421881}. This comparison identified many variables previously reported to differ between the two groups, but the statistically strongest indicators were "tic-related obsessive-compulsive behaviors" and a family history of tics, both of which were much more common in typical TS.  Another interesting study on this topic by the same group \citep{Cavanna2023a} compared 66 patients with FTLB with 44 patients with other functional movement disorders (FMD), namely functional symptoms suggesting dystonia, tremor, gait disorder, and myoclonus. While both groups shared some characteristics such as female preponderance, comorbid anxiety, depression, other functional neurological symptoms, and subacute onset of symptoms, patients with FTLB had an earlier age of symptom onset and were more frequently exposed to social media than those with other forms of FMD.  
Fremer and colleagues \citep{Fremer2024} compared a group of patients with FTLB (n=32) with a very large sample of patients with tics (n=1032). A number of previously reported characteristics of FTLB could be replicated: older age of onset, higher proportion of females, and higher rate of obscene and socially inappropriate behaviors. Interestingly, patients with FTLB had significantly lower rates of psychiatric comorbidities typically seen in TS such as ADHD and OCD. Phenotypic differences between  patients with FTLB (n=53) and tics (n=200) were also analyzed by a group of researchers from Denmark \citep{Andersen2023a}. Patients with FTLB were found to have more complex symptoms, were older at symptom onset, were more frequently females, and had less frequently a positive family history for tics. As a new finding, they reported that patients with FTLB had more family members with psychiatric disorders and more often had a history of trauma preceding the onset.  In another Danish study, Okkels and colleagues described a cohort of patients with FTLB \citep{Okkels2023}. Again, most were females, and had mainly complex movements with no rostrocaudal progression. Almost 70% reported harmful behaviors, and 96% had exposure to relevant social media.   
As noted above, patients with TS are not immune from developing FTLB in addition to pre-existing developmental tics. This association is not surprising, as for example pseudoseizures are more common in people with epilepsy. \citet{Müller-Vahl2024} presented data on 71 TS patients whom they also diagnosed with FTLB. A majority (56%-79%) had psychological features common in people with other functional symptoms, and about a third of them had a history of other medically unexplained symptoms; these findings suggest that the cause of FTLBs is likely similar to that of other functional neurological symptoms. The authors comment that their ability to identify a fairly large sample of TS+FTLB suggests that clinicians faced with treatment-resistant symptoms in TS should consider whether the symptoms are FTLB rather than tics.
Finally, an international group of experts published results of the so far largest group of patients with FTLB seen in multiple centers across the globe \citep{Martino2023}. Altogether, 294 patients with FTLB were included. The vast majority were adolescents and young adults (97%), 87% were females, 70% presented with rapid symptom progression, and spontaneous remission was noted in 20% of cases. From the phenomenological perspective, 85% demonstrated complex movements and 81% complex vocalizations. One fifth had a preexisting tic disorder, 66% had anxiety, around 30% depression, 24% autism, and 23% ADHD. Again, a high number (60%) reported exposure to social media. 
Diagnostic agreement in assessing FTLB was examined by asking eight experts in diagnosing and treating patients with tics to evaluate videos from 24 adults and diagnose them with either functional tics, primary tics or both \citep{Rigas2023}. The diagnostic agreement was based on phenomenology alone, and increased to moderate when additional clinical information was provided. However, the diagnostic distinction between primary and functional tics was shown to be difficult in the absence of clinical information.
Regarding long-term prognosis in 83 youth 83 youth with FTLB, Nilles and colleagues observed a meaningful improvement of FTLB over a period of 12 months suggesting an overall good prognosis \citep{Nilles2024}. 

Comorbidities

Sadeh and colleagues examined the presence of depressive symptoms in a cohort of 85 children and adolescents with chronic tic disorders (CTD), aged 6-18 years, using the Child Depression Inventory \citep{Sadeh2023}. In total, 21% had depressive symptoms and the presence of depressive symptoms was correlated with the presence of comorbid OCD and/or ADHD. Furthermore, symptoms of depression moderated the correlation between tic-related impairment and tic severity. Therefore, the authors suggest that it is important to screen and treat depression in children with CTD. 
The presence of depression and anxiety were assessed in several other studies. Isaacs and colleagues examined a population of 120 adult patients with CTD with several scales as part of routine care \citep{Isaacs2023}. Symptoms of anxiety were more common than depressive symptoms. Anxiety, depressive and OCD symptom severity were significantly associated to each other, but not to tic severity. In a systematic review and meta-analysis including twelve studies from 1997-2022, the prevalence of anxiety and depression in TS was estimated at 36.4% and 53.5% respectively \citep{Abbasi2023}
Koenn and colleagues examined impulsivity in its multidimensional aspects (Koenn et al., 2023a). They compared 16 patients with OCD, 14 patients with TS and 28 healthy subjects using the self-rated Barratt Impulsiveness Scale BIS-11 (attentional, motor, non-planning) and a continuous performance test assessing sustained attention, working memory, and cognitive impulsivity. Both patients with OCD and patients with TS showed significant deficits in attention via self-assessment, but no difference was observed in the behavioral test. Tic severity was strongly correlated with attentional impulsivity. The authors concluded that a detailed interpretation of the various tools for measuring impulsive behavior is necessary.