Tourette syndrome (TS) is a neurodevelopmental condition characterized by the presence of concomitant multiple motor tics and, at least one, vocal tic, that occurs for more than 1 year, in a patient <18 years old (1); DSM-V. The prevalence was even estimated to be 0.3–1% (2, 3), TS is more common in boys than in girls with a male-to-female ratio of 3–4/1 (4). Only 10–15% of individual patients with TS have tics only (pure TS) while the remaining patient population manifests comorbid attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive behaviors/obsessive-compulsive disorder (OCB/OCD), autism spectrum disorders (ASD), learning disabilities (LD), or other psychopathologies such as conduct disorder (CD), oppositional defiant disorder (ODD), anxiety disorders (AD) and depression (5, 6). Tics and co-occurring conditions are associated with functional impairment and contribute to decreases quality of life (7, 8). The etiology is complex and multifactorial. TS is polygenic, involving multiple common risk variants combined with rare, inherited or de novo mutations. These as well as non-genetic factors (such as perinatal events and immunological factors) are likely to contribute to the heterogeneity of the clinical phenotype, the structural and functional brain anomalies, and the neural circuitry involvement (4). Recently, the European Society for the study of Tourette Syndrome (ESSTS) wrote guidelines for the management of TS recommending psychoeducation as the initial intervention, and behavior therapy (BT) as a first-line intervention when psychoeducation alone is insufficient (9). Two approaches, habit reversal training (HRT; and its expanded version, Comprehensive Behavioral Intervention for Tics; CBIT) and exposure with response prevention (ERP), have gatered the strongest empirical support. (10–13). In situations where BT are ineffective, not available, not age-appropriate, or not the patient's or the family's preference, then pharmacological treatments should be considered.

The global pandemic caused by COVID-19 has created rapid changes to how people are able to carry out their normal lives, with impacts ranging from health and mortality through to those impacts brought about by social isolation rules and localized lockdowns. The social contexts for children and young people during this last year have been markedly different to what they had experienced before. Indeed, they have been subject to disrupted education at school and university, as well as hampered transition into training or the workforce for the first time (14, 15). Early results have indicated that adolescents may show an increase in symptoms of depression and anxiety, and that these are more concerned about the government restrictions designed to contain the spread of the virus, than the virus itself (16). Thus, they need our reassurance and help in these difficult times, supported by a network of informed health-care professionals. Perceived changes in tic severity during the lockdown were also recently described in school-age patients with tic disorders (17). In addition, during the global pandemic caused by COVID-19, it was reported a dramatic increase in functional tic-like behaviors in vulnerable children and adolescents after social media exposure (18, 19).

A promising development in increasing accessibility to behavioral treatments is the use of digital health interventions (DHIs) (20). Preliminary results suggest the effectiveness of DHIs for children and adolescents affected by tic disorders (21–23). In fact, telehealth will play an increasing role in the medical follow-up of patients with TS, likely beyond the end of the pandemic. However, it will be important to establish whether this type of care will be well accepted by patients and families alike (24).

This pilot study was conducted at the Child and Adolescent Neurology and Psychiatry of the Medical and Experimental Department of Catania University. A total of 40 patients with a diagnosis TS, according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-V), have been enrolled. Participants were randomly assigned to the face-to-face (ftf, n = 20) or online remote (or, n = 20) BT, using a simple randomization plan based on a random number list. Prior to enrolment, all participants provided written informed consent after receiving a complete explanation of the study and the assurance that the decision to participate in the study would not interfere with their treatment in any way. All parents gave written informed consent, and the subjects assented when possible. The study was conducted in accordance with the Declaration of Helsinki and approved by the local Ethics Committee (Catania 1) of Catania University Hospital.

Eligible participants were patients aged 9–16 years of age with a primary diagnosis of TS according to DSM-V criteria (1), recruited from September 2020 to May 2021 at the outpatient clinic of the Child and Adolescent Neuropsychiatry Unit at Catania University Hospital. The inclusion criteria were tics of moderate severity as measured by the Yale Global Tic Severity Scale (YGTSS; >13 for subjects affected by TS and >9 for those affected by CTD) (25), and an intelligence quotient (IQ) >80. Exclusion criteria were primary psychiatric disorders different from TS, intellectual disability, previous BT for tics or initiation or adjustment of any psychotropic medication for tic within the previous 2 months. Comorbid ADHD, OCD, or AD was not considered exclusion criteria unless the disorder required immediate treatment or a change in the current treatment regimen.

The clinical assessment of the patients was performed at two time points during the study by a pediatric neuropsychiatrist (R.R.) with solid experience in tic disorders and possible comorbidities. Participants underwent the first assessment at baseline (T0), the second after 2 months (T1). At T0, the Wechsler Intelligence Scale for Children (WISC-IV) was administered to evaluate the IQ of patients (26). At baseline point (T0), patients were also assessed according to Yale Global Tic Severity Rating Scale (YGTSS), Children's Yale-Brown Obsessive-Compulsive Scale for Children (CY-BOCS), Premonitory Urge for Tic Scale (PUTS), Multidimensional Anxiety Scale for Children (MASC), Child Depression Inventory (CDI) and the Conners' Parent Rating Scale (CPRS). Furthermore, after 2 months (T1), changes in symptoms severity were evaluated by the difference in the YGTSS, CY-BOCS, CPRS, CDI and MASC scales.

The YGTSS is a clinician-rated scale used to assess the motor and phonic tic severity considering the number, frequency, duration, intensity, and complexity of tics. It consists of separate motor and vocal tic checklists scored from 0 to 5 on two subscales for motor and vocal tics. The subscales were combined to produce a total tic severity score (ranging from 0 to 50). Another score ranging from 0 to 50 was assigned for global impairment due to tics (25).

The PUTS measures sensory and mental phenomena associated with premonitory urges in 10 items on a four-point scale (range 10–40). The first 6 items include itchiness, energy, pressure, tense feeling, incomplete, or a not “just right” feeling before performing a tic. The additional 4 items assess whether these feelings are experienced almost all the time before a tic, if they happen with every tic, if they go away after the tic is performed, and if subjects can stop the tics for a short period of time (27). To evaluate OCD, commonly associated with TS or CTD, the CY-BOCS, a semi-structured clinician-administered interview assessing the severity of obsessions and compulsions occurring over the past week across five areas (time, interference, distressing nature, effort to resist, control over obsessions and compulsions) was also administered (28). The CPRS is a useful tool for obtaining parental reports of childhood behavior problems that contains summary scales supporting ADHD diagnosis and quantifying ADHD severity (29). Finally, all participants completed the MASC, a self-report scale that robustly represents the factor structure of anxiety in children aged 8–18 years (30) and the Child Depression Inventory: a 27-item self-report instrument that assesses depressive symptoms in 7- to 17-year-olds (31).

BT was conducted according to the therapist manual developed by Verdellen et al. (32). Either HRT or ERP were conducted over eight weekly sessions. Sessions were 60 min in length. In awareness training, the therapist helps the patient to recognize the premonitory urge and to generate voluntary competing responses that are incompatible with the tic (habit reversal training) and/or increase their tolerance to the premonitory urge (exposure with response prevention). A ranking of the patient's tics is constructed according to tic severity and level of impairment, and then the patient learns to perform a voluntary movement to physically prevent performance of the tic during the competing response training. Patients were required to practice at home and parents were required to monitor tics for 15 min every day.

To perform or-BT was used Skype©, a peer-to-peer VoIP software application providing free web-based videoconferencing and utilizing security features (including standard encryption algorithms and digital user authentication certificates). Treatment was delivered from a private clinic room, using a desktop computer and a high-speed university-based internet connection. All participants used their own home computer, high speed internet connection, and a web camera to connect with the therapist.

Categorical variables are summarized by absolute and percent frequencies, and differences between the two treatment groups were analyzed by the Fisher's exact probability test. Quantitative variables are summarized by means, standard deviations (SD), medians and range (minimum; maximum). We assessed the distribution of quantitative variables to determine their deviation from the normal distribution within each treatment group (Shapiro–Wilk test) and the homogeneity of variance among the two treatment groups (Levene test). Since the distribution of the test scores (YGTSS, YBOCS, MASC, CDI, CONNERS) was not normal in some treatment groups at some time points, we assessed the differences between groups and time-points by non-parametric methods. Specifically, for any subject and any variable we computed the mean (T1+T2)/2 (YGTSS_m, YBOCS_m, MASC_m, CDI_m, CONNERS_m) and the variation (T1-T2) (YGTSS_d, YBOCS_d, MASC_d, CDI_d, CONNERS_d) between the values at the two time-points. We then performed the Mann-Whitney U test to assess the difference between the two treatment groups in the mean values (main effect of treatment) and in the variations (interaction treatment-by-time), and the Wilcoxon matched paired test to assess the main effect of time. In the presence of a significant interaction treatment-by-time, we repeated the Wilcoxon test separately in the two treatment groups, applying the Bonferroni's correction to account for the two comparisons. Statistical analyses were performed using STATA release 16.0 software.

In this study, we enrolled a total of 40 subjects aged 9–16 years (Mean age = 13,5 ± 2,0; male (M)/female (F) = 36:4; male = 90,0%). All patients were affected by TS. The mean age of tic onset was 5,8 ± 1,2. Among the individuals diagnosed with TS, the most common comorbid psychiatric disorders were OCD (60%, n = 24), LD (42,5%, n = 17) and anxiety disorder (42,5%, n = 17). None of the patients had a concomitant depression, and only one patient was also affected by epilepsy. Only seven patients (17,5%) presented “pure-TS” phenotype. Seventeen (42,5%) received a pharmacological treatment (1 drug in 9, 2 drugs in 4, 3 drugs in 4) with no good response or a partial symptoms control. Participants presented a mean IQ of 103,8 (±10,6) and a mean PUTS score of 13,3 (±2,6). Demographic data and clinical features of all participants are displayed in Table 1.

At baseline, no statistically significant differences were observed based on neuropsychological findings in the ftf- BT group vs. the or-BT group. The mean scores for YGTSS, CY-BOCS, and MASC were slightly lower in the or-BT group vs. the ftf-BT group (YGTSS: mean 25.5, SD 10.5 vs. mean 25.8, SD 7.3, p = 0.773; CY-BOCS: mean 22.3, SD 12.0 vs. mean 22.7, SD 12.7, p = 0.644; MASC: mean 35.05, SD 16.8 vs. mean 36.15, SD 15.3, p = 0.663). Conversely, the mean scores for CPRS and CDI were slightly higher in the or-BT group vs. the ftf-BT group (CPRS: mean 21.15, SD 22.4 vs. mean 20.15, SD 17.2, p = 0.363; CDI: mean 4.45, SD 1.9 vs. mean 4.3, SD 2.6, p = 0.574).

In general, patients in both groups showed a reduction in the severity of tic symptoms, as assessed by YGTSS scores, at T1. Mean YGTSS score at 2 months after randomization was 14,1 (SD 6,3) in the or-BT -group compared with 13,7 (SD 5,35) in the ftf-BT -group. The mean total decrease in YGTSS at 2 months was 12,05 (46,8%) in the ftf-BT -group vs. 11,4 (44,7%) in the or-BT -group. No statistically significant differences were observed between the ftf-BT group vs. or-BT –group in the variation of the severity of tics as assessed by YGTSS between T0 and T1 (p = 0.702) (Table 2, Figure 1).

Patients in both groups showed a reduction in the severity of obsessive-compulsive symptoms, as assessed by CYBOCS scores, at T1. Mean CYBOCS score at 2 months after randomization was 22,3 (SD 12,0) in the or-BT -group compared with 22,7 (SD 12,7) in the ftf-BT -group. The mean total decrease in CYBOCS at 2 months was 7,65 (33,7%) in the ftf-BT -group vs. 8,05 (36,1%) in the or-BT -group. No statistically significant differences were observed between the ftf-BT group vs. or-BT –group in the severity of obsessive-compulsive symptoms as assessed by CYBOCS between T0 and T1 (p = 0.680) (Table 2, Figure 1).

Patients in both groups showed a reduction in the severity of core-ADHD symptoms, as assessed by CPRS scores, at T1. Mean CPRS score at 2 months after randomization was 21,15 (SD 22,4) in the or-BT -group compared with 20,15 (SD 17,2) in the ftf-BT -group. The mean total decrease in CPRS scores at 2 months was 5,45 (27,05%) in the ftf-BT -group vs. 6,85 (32,4%) in the or-BT -group. No statistically significant differences were observed between the ftf-BT group vs. or-BT –group in the variation of the severity of these symptoms as assessed by CPRS between T0 and T1 (p = 0.928) (Table 2, Figure 1).

Patients in both groups showed an improvement in MASC scores at T1. Mean MASC score at 2 months after randomization was 35,05 (SD 16,8) in the or-BT -group compared with 36,15 (SD 15,3) in the ftf-BT -group. The mean total decrease in MASC at 2 months was 13,6 (37,6%) in the ftf-BT group vs. 13,5 (38,5%) in the or-BT -group. No statistically significant differences were observed between the ftf-BT group vs. or-BT –group in the variation of the severity of anxiety symptoms as assessed by MASC between T0 and T1 (p = 0,804) (Table 2, Figure 1).

Patients in both groups showed an improvement in CDI scores at T1. Mean CDI score at 2 months after randomization was 4,45 (SD 1,9) in the or-BT -group compared with 4,3 (SD 2,6) in the ftf-BT -group. The mean total decrease in CDI at 2 months was 0,05 (1,16%) in the ftf-BT group vs. 1,05 (23,6%) in the or-BT -group. Statistically significant differences were observed between the ftf-BT group vs. or-BT –group in the severity of depressive symptoms as assessed by CDI between T0 and T1 (p = 0.002) (Table 2, Figure 1).