INTRODUCTION

In 2022, in response to a surge in the number of patients with functional tic-like behaviours (FTLBs) at many centres worldwide [1-9], the European Society for the Study of Tourette Syndrome (ESSTS) developed criteria for the clinical diagnosis of FTLBs [10]. These criteria were developed by experts in the diagnosis of tic disorders, using a formal consensus development process. Three major criteria and two minor criteria were proposed to support the diagnosis of FTLBs, with a clinically definite diagnosis confirmed by the presence of all three major criteria and a clinically probable diagnosis confirmed by the presence of two major criteria and one minor criterion [10]. The major criteria included (1) age of onset of 12 years or older, (2) rapid onset and evolution of symptoms and (3) at least four of nine phenomenological features [10]. Phenomenological features suggestive of FTLBs included the presence of more complex than simple tic-like behaviours, complex arm and hand movements such as banging chest/head, tapping, hitting others, sign language, throwing objects, offensive gestures, drop attacks or freezing, and complex vocal tic-like behaviours such as several words, statements, context-dependent and offensive words/statements [1].

The ESSTS criteria for FTLBs require testing of their sensitivity and specificity. Our objective was to test the specificity of selected criteria (age of onset and specific phenomenological criteria) in children with primary tic disorders (PTDs) enrolled in the Calgary Tic Disorder Registry prior to and after the onset of the SARS-CoV-2 pandemic and of the development of the ESSTS criteria for FTLBs.

METHODS

Children and adolescents with PTDs have been prospectively included in our Tic Disorder Registry at the Calgary Tourette and Paediatric Movement Disorder Clinic at the Alberta Children's Hospital in Calgary, Canada, since 2017. PTDs, including Tourette syndrome, persistent motor and phonic tic disorders and provisional tic disorders, were defined according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [11].

In this cross-sectional study, sex, age at first clinical assessment and age at tic onset were recorded. Tics at the first clinical assessment were evaluated using the Yale Global Tic Severity Scale (YGTSS), which includes a detailed tic inventory collected with reference to the past week. The proportion of youths with PTDs who reported a tic onset at ≥12 years was evaluated, to assess the specificity of the age criterion of FTLBs. Using the YGTSS, the proportion of youths with PTDs who met specific phenomenological criteria for FTLBs at their first clinical visit was assessed, to determine their specificity: (1) the presence of specific complex motor tics commonly seen in FTLBs (complex arm movement, complex hand movement, self-injurious behaviour, blocking or copropraxia), (2) the presence of specific complex vocal tics commonly seen in FTLBs (saying words or phrases, disinhibited speech or coprolalia) and (3) the presence of a greater number of complex than simple tics. The specificity of having a combination of one or two complex motor tics and one complex vocal tic at the first clinical visit was assessed. To evaluate the presence of a historical bias, the main analyses in children included between 2017 and 2019 were performed and compared with data collected from registry participants between 2021 and 2023. Due to pandemic-related restrictions in research activities and operational constraints, no participants were registered in the year 2020. Longitudinal follow-up data assessing for subsequent diagnosis of FTLBs in all participants who were aged 12 or older at tic onset, who had a combination of one complex motor and one complex vocal tic, or who had more complex than simple tics at their first visit were reviewed.

Data were summarized using means, 95% confidence intervals (CIs) and percentages, for the whole sample and for those participants aged 12 or older at their first clinical visit, to determine if there were any substantial differences in phenomenology based on age. A t test was used to compare means when needed. Statistically significant differences between estimates of specificity were determined by assessing for overlap of the 95% CIs. All statistical analyses were performed using StataCorp (College Station, TX, USA).

This project received ethical approval from the University of Calgary Conjoint Health Research Ethics Board. Parents provided signed informed consent and children provided assent to study participation and publication of the study results.

RESULTS

A total of 156 participants were included in the Registry in Calgary, Canada, between 2017 and 2019. Fifty-five (35.3%) had their first visit at age 12 or older. Males represented 78.2% of participants. In youths aged 12 or older at inclusion, mean age of tic onset was 7.6 years (95% CI 6.6–8.6) and latency between age of tic onset and age at first visit was 6.6 years (95% CI 5.6–7.6). Table 1 summarizes demographics, diagnoses and tic severity scores of our population. Demographic features of children registered from 2021 to 2023 (n = 149) were similar to children included from 2017 to 2019.

In the 2017–2019 cohort, only eight of 139 (5.8%) children and adolescents had an age of tic onset ≥12 years, leading to a specificity of the age criterion of 94.2%. Similarly, in the 2021–2013 cohort, specificity of the age criterion was 91.4%.

At the time of inclusion, youths in the 2017–2019 cohort reported 5.2 simple tics on average during the past week, versus 2.2 complex tics. There was no significant difference in the number of simple or complex tics based on participant age or the time period studied.

Table 2 shows the specificity of FTLB clinical diagnostic criteria based on participant age and time period. In youths aged 12 or older at inclusion from 2017 to 2019, (1) blocking and copropraxia were found in <10% of participants, whereas complex arm (20%) and hand (31%) movements and self-abusive behaviours (18%) were not rare; (2) the complex phonic tics commonly seen in FTLBs (saying words or phrases, disinhibited speech and coprolalia) were found in <10% each. Twenty-five of 55 adolescents (45.5%) aged 12 or older at inclusion had at least one of the complex motor tics commonly seen in FTLBs, whilst 13 had two (23.6%). Seven (12.7%) had at least one of the complex phonic tics commonly seen in FTLBs. The specificity of having at least two complex motor tics and at least one complex vocal tic commonly seen in FTLBs was 94.5%. In adolescents aged 12 or older at inclusion, the specificity of the FTLB diagnostic criterion of having more complex tics than simple tics was 85.5% (Table 2).

When comparing children with PTDs included between 2017 and 2019 with those included from 2021 to 2023, it was found that the specificity of the ESSTS criteria was similar (Table 2), with no significant differences in estimates of specificity. Longitudinal follow-up of all 36 patients included between 2017 and 2019 with at least one of the specified ESSTS criteria showed that the diagnosis of Tourette syndrome (TS) was changed to FTLBs in one child, and FTLBs were diagnosed in comorbidity with the diagnosis of TS in two. A similar longitudinal review of 34 patients included between 2021 and 2023 showed that FTLBs were diagnosed in addition to TS in two children.

DISCUSSION

This study evaluates the specificity of individual ESSTS criteria to diagnose FTLBs (age at onset and selected features of the phenomenological criteria) at the time of first visit in a specialist clinic. Across groups and time periods studied, high specificity of the age at onset criterion and having at least two complex motor and one complex vocal tic at the time of first visit were observed. Amongst the complex motor tics, some had lower specificity (complex arm and hand movements and self-abusive behaviours) when assessed individually. The requirement in the ESSTS criteria to fulfil at least four of nine phenomenological criteria for the diagnosis of FTLBs appears well justified.

There is still considerable diagnostic uncertainty in the differentiation between primary tics and FTLBs. A recent study assessing diagnostic agreement between experts demonstrated suboptimal agreement when diagnostic judgement is exclusively based on the phenomenology reviewed through videos [12]. The level of agreement increased when age at onset and rapidity of symptom evolution were provided to raters, albeit remaining suboptimal. Unlike in that agreement study, in which patients were not specifically recorded during the first clinic visit, the present dataset refers to the first diagnostic encounter at a specialist clinic. Early recognition and diagnosis are highly relevant for patient communication and to initiate a correct management approach, which was found to be associated with better outcome of FTLBs [13]. The optimal specificity observed for the combination of the two explored criteria indicates a very low likelihood of misdiagnosis at first visit if these criteria are fulfilled.

The present study did not evaluate sensitivity of the ESSTS criteria. Recently, Cavanna et al. measured the sensitivity of the ESSTS criteria, reporting a sensitivity of 74% for the ‘clinically definite’ diagnosis of FTLBs, with 10% of patients fulfilling criteria for ‘clinically probable’ FTLBs, thus confirming optimal sensitivity for the combination of these two criteria-based diagnostic categories [14]. The study of these authors provides support to the accuracy of the ESSTS criteria and to their potential usefulness when screening for the diagnosis of FTLBs.

The ESSTS criteria show good specificity in the cohort of children and adolescents with TS included from 2017 to 2019, prior to the SARS-CoV-2 pandemic. This underlines that the criteria can be useful for distinguishing PTDs and FTLBs at different time periods, with no statistically significant change in specificity to suggest ‘circular reasoning’. If this were the case, specificity would have significantly increased in the 2021–2023 cohort.

This study has obvious limitations. The data in our registry did not allow for measuring the specificity of the rapid symptom onset and evolution criterion, as this information was not systematically recorded prior to the rise in FTLB cases. However, the relatively long latency between onset and first evaluation in our specialist clinic might suggest that most patients with PTDs did not experience rapid evolution of symptoms, although confirmation of this is needed. The very low frequency of the complex behaviours that are observed consistently in FTLB cases may also not have been captured by the YGTSS inventory, which was designed specifically for PTD, whereas rating instruments for FTLB are lacking. Considering our results, and that some studies suggest that functional overlay in patients with PTDs is not rare [1, 14], it cannot be excluded that the specificity figures could be underestimated. Our longitudinal follow-up of children in both cohorts who met age or specific phenomenological criteria found four children who subsequently developed FTLBs and one child whose diagnosis was revised from TS to FTLBs. Finally, the single-site study design may limit the generalizability of the specificity findings reported here.

In conclusion, ours is the first study reporting very high specificity for the ESSTS diagnostic criteria of FTLB. This information, coupled to that reported by Cavanna et al. with respect to sensitivity [14], further supports the use of these criteria in clinical practice, at the time of first evaluation. Future work should assess the specificity of the remaining criteria/features of this set of diagnostic criteria and evaluate whether the application of the ESSTS criteria in routine clinical practice confirms its positive impact on prognosis.

AUTHOR CONTRIBUTIONS

Christelle Nilles: Conceptualization; methodology; software; writing – original draft; formal analysis; writing – review and editing. Davide Martino: Conceptualization; methodology; writing – review and editing; writing – original draft; supervision. Tamara Pringsheim: Conceptualization; methodology; writing – review and editing; writing – original draft; supervision.

FUNDING INFORMATION

CN received salary support from the French Gilles de la Tourette Association (AFSGT) and the Owerko Centre of Alberta Children's Hospital Research Institute in 2021–2022. DM has received compensation for consultancies for Sunovion and Merz Pharmaceuticals, honoraria from Dystonia Medical Research Foundation Canada and Merz Pharmaceuticals, royalties from Springer-Verlag and Oxford University Press, funding grants from Dystonia Coalition-RDCN-NIH plus Dystonia Medical Research Foundation and Dystonia Medical Research Foundation Canada, and National Spasmodic Torticollis Association (NSTA) Sacramento Chapter, the Owerko Foundation, Weston Family Foundation and the Michael P. Smith Family. TP received research funding from the Canadian Institutes of Health Research and the Azreili Accelerator of the University of Calgary.

CONFLICT OF INTEREST STATEMENT

None.