European Society for the Study of Tourette Syndrome 2022 criteria for clinical diagnosis of functional tic-like behaviours: International consensus from experts in tic disorders.

BACKGROUND AND PURPOSE: In 2020, health professionals witnessed a dramatic increase in referrals of young people with rapid onset of severe tic-like behaviours. We assembled a working group to develop criteria for the clinical diagnosis of functional tic-like behaviours (FTLBs) to help neurologists, pediatricians, psychiatrists, and psychologists recognize and diagnose this condition. METHODS: We used a formal consensus development process, using a multiround, web-based Delphi survey. The survey was based on an in-person discussion at the European Society for the Study of Tourette Syndrome (ESSTS) meeting in Lausanne in June 2022. Members of an invited group with extensive clinical experience working with patients with Tourette syndrome and FTLBs discussed potential clinical criteria for diagnosis of FTLBs. An initial set of criteria were developed based on common clinical experiences and review of the literature on FTLBs and revised through iterative discussions, resulting in the survey items for voting. RESULTS: In total, 24 members of the working group were invited to participate in the Delphi process. We propose that there are three major criteria and two minor criteria to support the clinical diagnosis of FTLBs. A clinically definite diagnosis of FTLBs can be confirmed by the presence of all three major criteria. A clinically probable diagnosis of FTLBs can be confirmed by the presence of two major criteria and one minor criterion. CONCLUSIONS: Distinguishing FTLBs from primary tics is important due to the distinct treatment paths required for these two conditions. A limitation of the ESSTS 2022 criteria is that they lack prospective testing of their sensitivity and specificity.

Impact of Tourette Syndrome on Education.

BACKGROUND: Previous studies have shown that Tourette syndrome (TS) has an impact on academic achievements. The aim of this study was to investigate the association between the severity of tics and comorbidities and educational outcomes. METHODS: From 2005 to 2007, 395 participants were included in a large cohort (314 with TS and 81 controls) and the mean age was 12.60 ± 2.64 years. The cohort was re-examined after 4 to 8 years (median 5.6) where n = 276 participants (223 with TS and 53 controls) were included with a mean age of 18.52 ± 2.73 years. At both time points, severity of tics and the presence and severity of psychiatric comorbidity were assessed. Educational achievements were assessed through structured interviews. RESULTS: Children with TS had a lower passing rate at lower secondary and high school compared to healthy controls. More severe vocal tics were associated with fewer passing lower secondary school at a prospective level. At a cross-sectional level, more severe motor tics were associated with fewer passing high school. Tic severity only influenced children with TS without comorbidity. The severity of comorbidity was found to be associated with the educational level at a longitudinal view, but not cross-sectional. CONCLUSION: Overall, children with TS had a lower passing rate at lower secondary school and high school compared to healthy controls. We found that this difference was more likely driven by the severity of comorbidities than tic severity. It is important to be aware of academic achievement in children with TS in order to give them the right support and thereby optimize educational opportunities.

Exposure and Response Prevention: Evaluation of Tic Severity Over Time for Children and Adolescents with Tourette Syndrome and Chronic Tic Disorders.

Tourette syndrome and chronic tic disorders are characterized by the presence of tics. Different behavioral therapies have shown to be efficacious for treating tics in children and adolescents, but Exposure and Response Prevention (ERP) is a less researched method. However, ERP is a method often used in the clinical setting. Therefore, the present study evaluated the severity of tics over time from beginning of ERP to follow-up approximately 1 year after last training session.In total, 116 patients treated with ERP face to face or ERP via web-based videoconferencing were included. The primary outcome measure was tic severity measured with the Danish version of the Yale Global Tic Severity Scale.The results showed that tic severity decreased during ERP and lasted in the follow-up period, with a statistically higher decrease in the group with patients who completed ERP as planned and the group that stopped earlier than planned because of reduction in tics, compared with those who dropped out due to lack of motivation (p < 0.001).The study concludes that ERP seems to have an immediate and a long-term effect on severity of tics, especially in those who complete the program or those who discontinue earlier due to good results.

Exposure and Response Prevention for Children and Adolescents with Tourette Syndrome Delivered via Web-Based Videoconference versus Face-to-Face Method.

Chronic tic disorders, such as Tourette syndrome, are characterized by motor and vocal tics. Tics present a considerable burden for some patients, and therefore, effective treatment is important. One evidence-based treatment option is a behavioral therapy called exposure and response prevention (ERP). Despite its effectiveness, access to ERP remains limited due to a lack of treatment sites. Web-based videoconferences can connect patients at home with a therapist located in the hospital, allowing for treatment delivery over a wide geographic area. The primary aim of this study was to compare the development of tics during and 1 year after ERP delivery, respectively, via web-based videoconferences and traditional face-to-face methods in a naturalistic setting. In total, 116 patients treated using either the face-to-face method (n = 72) or web-based videoconferences (n = 44) were included. The primary outcome measure was tic severity. In both training modalities, tic severity decreased during ERP and the effect lasted in the follow-up period. No statistically significant differences in tic severity between the training modalities were found at baseline, last training session, or at follow-up. Our results suggest that ERP delivered via web-based videoconferences is a good alternative to the traditional face-to-face method.

Increased Number of Functional Tics Seen in Danish Adolescents during the COVID-19 Pandemic.

BACKGROUND: Global increase in functional tics in adolescents has been observed. Differentiating functional from classic tics is important since pathophysiology and treatment differ. We investigated possible triggers for development of functional tics and discuss the possible role of the coronavirus disease 2019 (COVID-19) pandemic and social media exposure in cases of functional tics seen during this period. Moreover, the treatment, and its efficacy is discussed. METHODS: Medical records of 28 Danish adolescents diagnosed with functional tics at the National Tourette Clinic, Department of Pediatrics, Herlev University Hospital, Denmark, from May 2020 to June 2021 have been retrospectively reviewed. Descriptive statistical analyses were used to analyze the data. MAIN FINDINGS: A total of 28 patients diagnosed with functional tics were included, 96.4% girls and 3.6% boys, mean age 14.4 years. Tic phenomenology differed from classic tics with more complex tics and no rostrocaudal progression. Note that 69.2% reported harmful tics. Also, 78.6% had trauma/precipitating event and 40% denounced lockdown related to the COVID-19 pandemic as trigger, both prior to onset of functional tics. Note that 60.7% reported psychiatric symptoms/diagnoses, 42.9% had a first-degree family member with psychiatric symptoms/diagnoses, and 96.4% were exposed to tics on social media prior to onset. Treatment consisted of psychoeducation, elements from cognitive behavioral therapy, and focus on psychiatric symptoms. All patients responded to the treatment. CONCLUSION: The vulnerability of the adolescents is characteristic. Treatment strategy has shown immediate positive effect. Consequences of the COVID-19 pandemic in combination with exposure to tics on social media could be part of the cause for the increase in number of functional tics.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part I: assessment.

In 2011 a working group of the European Society for the Study of Tourette Syndrome (ESSTS) has developed the first European assessment guidelines for Tourette syndrome (TS). Now, we present an updated version 2.0 of these European clinical guidelines for Tourette syndrome and other tic disorders, part I: assessment. Therefore, the available literature has been thoroughly screened, supplemented with national guidelines across countries and discussions among ESSTS experts. Diagnostic changes between DSM-IV and DSM-5 classifications were taken into account and new information has been added regarding differential diagnoses, with an emphasis on functional movement disorders in both children and adults. Further, recommendations regarding rating scales to evaluate tics, comorbidities, and neuropsychological status are provided. Finally, results from a recently performed survey among ESSTS members on assessment in TS are described. We acknowledge that the Yale Global Tic Severity Scale (YGTSS) is still the gold standard for assessing tics. Recommendations are provided for scales for the assessment of tics and psychiatric comorbidities in patients with TS not only in routine clinical practice, but also in the context of clinical research. Furthermore, assessments supporting the differential diagnosis process are given as well as tests to analyse cognitive abilities, emotional functions and motor skills.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part III: pharmacological treatment.

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients' self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient's needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician's preferences, experience, and local regulatory requirements.

An observational study of emotion regulation in children with Tourette syndrome.

BACKGROUND: Explosive outbursts occur in 25%-70% of children with Tourette syndrome (TS) and may cause more distress than the tics themselves. Previous studies have indicated that a comorbid diagnosis of attention-deficit/hyperactivity disorder (ADHD) is associated with emotional dysregulation in TS; however, this relationship has almost exclusively been studied using parent-reported questionnaires. METHODS: We examined emotion regulation (ER) with an observational measure in 150 medication-naïve children aged 7-12 allocated to four groups: Forty-nine children with TS, 23 children with ADHD, 16 children with TS + ADHD, and 62 typically developing controls. We assessed participants' ER ability, as well as parent-child interactions in the context of a complex puzzle task, and coded the observed behavior with the Tangram Emotion Coding Manual (TEC-M). We examined group differences in ER, as well as associations between ER and severity of symptoms pertaining to TS and ADHD. RESULTS: Children with TS did not differ from controls in their ER ability. However, children with ADHD and TS + ADHD had more problems with ER than those with TS only and controls. Finally, parents of children with ADHD displayed more tension during the experimental task. ER ability was not associated with tic severity nor premonitory urges; however, better ER ability was associated with less severe symptoms of ADHD. CONCLUSIONS: This study is the first to evaluate ER with an observational, clinician-rated measure in a controlled social setting in children with TS. Our findings support earlier questionnaire-based studies by showing impaired ER in children with TS + ADHD, but not in children with TS without comorbidity. These findings inform our understanding of the phenomenology of emotional dysregulation in TS and the role of comorbid disorders.

Clinical guidance for diagnosis and management of suspected Pediatric Acute-onset Neuropsychiatric Syndrome in the Nordic countries.

Pediatric acute-onset neuropsychiatric syndrome is a clinical concept used to describe a subgroup of children with sudden onset of psychiatric and somatic symptoms. The diagnostic term and especially management of children differs depending on the clinical setting to which they present, and the diagnosis and management is controversial. The aim of this paper is to propose a clinical guidance including homogenous diagnostic work-up and management of paediatric acute onset neuropsychiatric syndrome within the Nordic countries. The guidance is authored by a Nordic-UK working group consisting of paediatric neurologist, child psychiatrists and psychologists from Denmark, Norway, Sweden and Great Britain, and is the result of broad consensus. CONCLUSION: Consensus was achieved in the collaboration on work-up and treatment of patients with paediatric acute-onset neuropsychiatric syndrome, which we hope will improve and homogenise patient care and enable future collaborative research in the field.

Study of medication-free children with Tourette syndrome do not show imaging abnormalities.

BACKGROUND: Imaging studies of patients with Tourette's syndrome (TS) across different cohorts have shown alterations in gray and white matter in areas associated with the cortico-striato-thalamic-cortical (CSTC) pathways; however, no consistent findings have subsequently established a clear indication of the pathophysiology of TS. METHODS: This study was designed to investigate changes in gray and white matter in medication-free children with TS in the CSTC areas. With MRI, 24 children with TS and 18 healthy controls were analyzed using three complementary methods. RESULTS AND CONCLUSION: Analyses revealed no differences between controls and patients with TS in gray or white matter. Possible discrepancies between cohorts and methods may play a role in the different findings in other studies. Further studies investigating well-defined cohorts with TS analyzing both gray and white matter in the same cohort may add additional information to the pathophysiology of TS.

Reduced neck-shoulder muscle strength and aerobic power together with increased pericranial tenderness are associated with tension-type headache in girls: A case-control study.

BACKGROUND: Tension-type headaches (TTH) are common among children worldwide and mean a potential risk of disability and medication overuse headache. The associated mechanisms, however, remain unsolved. Our study investigated muscle strength in the neck-shoulder region, aerobic power and pericranial tenderness in girls with TTH compared with healthy controls. METHODS: A blinded case-control study comprising 41 girls with TTH and 41 age-matched healthy controls. Standardised testing of isometric maximal voluntary contraction (MVC) and force steadiness of neck flexion and extension, as well as MVC and rate-of-force development of dominant shoulder, was conducted. VO2 max was recorded by a submaximal ergometer test and pericranial tenderness by standardised manual palpation. Logistic regression analyses were applied. RESULTS: Girls with TTH demonstrated significantly higher pericranial tenderness than controls, in correlation with headache frequency (r = 0.66, p < 0.001). Results indicated that the odds ratio of girls having headache are 7.6 (95% CI 1.4-40.9) for weak to strong shoulder muscles; weak to average neck-shoulder strength OR 3.1 (95% CI 1.2-8.1); neck flexion strength OR 1.3 (95% CI 1.0-1.6) and 5.2 (95% CI: 1.4-19.6) for each unit of decrease in VO2 max. CONCLUSIONS: Reduced neck-shoulder strength and aerobic power together with increased pericranial tenderness are associated with TTH in girls. Future interventions should be directed towards health promoting patient educational programmes on enhanced physical exercising. Much more exact and detailed research in young girls and boys are needed.

A Critical Examination of the Clinical Diagnosis of Functional Tic-like Behaviors.

BACKGROUND: Since the COVID-19 pandemic, movement disorder clinics have seen an increase in patients with an unusual type of tic-like symptoms: young adults with abrupt onset complex behaviors. It was quickly suspected that these patients suffered from functional neurological symptoms, later named Functional Tic-Like Behaviors (FTLB). Subsequent research on the differential diagnosis between FTLB and tics has been substantial and led to the development of diagnostic checklists. OBJECTIVES: We conducted a theoretical reappraisal of the FTLB literature to clarify the validity of the concept and its diagnostic implications. METHODS: This paper addresses several key aspects of the current FTLB literature: circular reasoning, the complications of the FTLB phenomenology and demographics, the impact of FTLB on tic literature at large, and issues with alignment of the FTLB concept with the diagnostic criteria for functional disorders. RESULTS: The clinical approach to FTLB might involve circular reasoning due to a lack of clinical benchmarks. The FTLB phenomenology and demographics may need more work to ensure a lack of bias and a proper description of this patient group including a clear distinction from tics. The impact of the FTLB discussion on the wider literature needs consideration. The validation of positive signs may help with both these endeavors and pave way to the inclusion of FTLB within psychiatric classification systems. Furthermore, the coexistence of FTLB and tics within the same patient needs to be addressed. CONCLUSION: More research may be needed to fully establish the diagnosis of FTLB and differentiate it from tics.

Chromosomal rearrangements in Tourette syndrome: implications for identification of candidate susceptibility genes and review of the literature.

Tourette syndrome (TS) is a childhood-onset complex neurobiological disorder characterized by a combination of persistent motor and vocal tics and frequent presence of other neuropsychiatric comorbidities. TS shares the fate of other complex disorders, where the genetic etiology is largely unknown, and identification of susceptibility genes through linkage and association studies has been complicated due to inherent difficulties such as no clear mode of inheritance, genetic heterogeneity, and apparently incomplete penetrance. Positional cloning through mapping of disease-related chromosome rearrangements has been an efficient tool for the cloning of disease genes in several Mendelian disorders and in a number of complex disorders. Through cytogenetic investigation of 205 TS patients, we identified three possibly disease-associated chromosome rearrangements rendering this approach relevant in chasing TS susceptibility genes.

Headache in children: effectiveness of multidisciplinary treatment in a tertiary paediatric headache clinic.

AIM: The aim of this article is to evaluate the effectiveness of a specific multidisciplinary treatment programme for children with headache and to describe the concept and settings of the Children's Headache Clinic in Denmark. METHOD: All new patients were included and evaluations were conducted after six and 12 months. Pharmacological and non-pharmacological treatments were offered by a team of specialists (physicians, headache nurses, a physiotherapist and a psychologist). PATIENTS: The subjects comprised 169 children (mean age 11.7 (range 4-17), 91 females, 78 males), 39% of whom suffered from chronic headache (≥15 days/month). All children were diagnosed according to the International Classification of Headache Disorders, second edition; 20% had migraine, 34% tension-type headache, 27% mixed headache, 4% medication-overuse headache, and 15% were diagnosed with other types of headaches. RESULTS: Fifty per cent of the children had an improvement in headache frequency above 50% at six months. By the use of repeated measurement analysis, we found a significant decrease in headache frequency in all of the six headache groups, whereas the increase in quality of life (PedsQL™ 4.0) was significant for the group as a whole. CONCLUSION: Though preliminary, the results show a good outcome for multidisciplinary treatment programmes for children who suffer from frequent or chronic headache.

Altered pain perception in children with chronic tension-type headache: is this a sign of central sensitisation?

AIM: The aim of this article is to investigate if children (7-17 years) with frequent episodic tension-type headache (FETTH) or chronic TTH (CTTH) have an altered pain perception compared to healthy controls. METHODS: We applied a pressure of five increasing intensities to m. trapezius and m. temporalis with a Somedic Algometer II. Visual analogue scale-score was rated and area under the curve (AUC) calculated. An average AUC in each person was used as an outcome variable in further univariate multiple linear regression analysis because factor analysis showed that AUC represents only one dimension underlying both muscles. RESULTS: Participants included 22 children with FETTH, 36 children with CTTH and 57 controls. The CTTH group had a significantly higher AUC compared to the control group ( P < 0.001). The FETTH group represented an intermediate state. AUC did not change with increasing age, headache years, headache intensity, headache frequency or sex. CONCLUSION: Children with CTTH show significantly increased pain sensitivity in a range of pressures compared to the FETTH group and the controls. Since AUC in m. trapezius and m. temporalis represents only one general latent tenderness, it might indicate that the altered pain perception is mainly due to central sensitisation.

Microduplication of 15q13.3 and Xq21.31 in a family with Tourette syndrome and comorbidities.

Tourette syndrome (TS) is a childhood onset neurodevelopmental disorder. Although it is widely accepted that genetic factors play a significant role in TS pathogenesis the etiology of this disorder is largely unknown. Identification of rare copy number variations (CNVs) as susceptibility factors in several neuropsychiatric disorders such as attention deficit-hyperactivity disorder (ADHD), autism and schizophrenia, suggests involvement of these rare structural changes also in TS etiology. In a male patient with TS, ADHD, and OCD (obsessive compulsive disorder) we identified two microduplications (at 15q13.3 and Xq21.31) inherited from a mother with subclinical ADHD. The 15q duplication included the CHRNA7 gene; while two genes, PABPC5 and PCDH11X, were within the Xq duplication. The Xq21.31 duplication was present in three brothers with TS including the proband, but not in an unaffected brother, whereas the 15q duplication was present only in the proband and his mother. The structural variations observed in this family may contribute to the observed symptoms, but further studies are necessary to investigate the possible involvement of the described variations in the TS etiology.

Childhood Comorbidity Severity Impacts Adolescent Substance Consumption in Patients With Tourette Syndrome.

BACKGROUND: This study explores the longitudinal impact of severity of Tourette Syndrome (TS), diagnosis and severity of Attention-Deficit/Hyperactivity Disorder (ADHD) and Obsessive-Compulsive Disorder (OCD), and guardian socioeconomic status on the level of substance use of pediatric patients with TS. METHODS: A total of 314 pediatric patients with TS participated at time 1 (T1). During these visits, the severity of the patients' TS, ADHD, and OCD symptoms were assessed, along with their guardians' socioeconomic status. At time 2 (T2), between four and eight years later (median 5.6 years), 227 patients returned for a follow-up. Here, the patients answered questions about their intake of alcohol, cigarettes, and illegal substances. The relationship between the patients' diagnoses, symptom severity, and socioeconomic status at T1 and reported substance use at T2 was then analyzed using binary logistic regression. RESULTS: Increased severity of ADHD and lower guardian socioeconomic status at T1 significantly increased the odds of later high cigarette consumption. Furthermore, both presence and increased severity of ADHD at T1 increased the odds of illegal substance consumption at T2. Conversely, increased severity of OCD at T1 significantly decreased cigarette and illegal substance consumption at T2, whereas both presence and increased severity of OCD decreased alcohol consumption. CONCLUSIONS: Pediatric patients with TS with increased ADHD severity have increased risk of consuming illegal substances and high amounts of cigarettes as adolescents, whereas increased OCD severity may act as a protective factor. Having preventative conversations about substance consumption with patients with TS with high ADHD severity is important.

Clarifying the Differences between Patients with Organic Tics and Functional Tic-Like Behaviors.

Due to the global increase in the number of patients with Functional Tic-Like Behaviors (FTLB), it has become increasingly important to find reliable differences between this patient group and patients with organic tics (OTs), which can be used in differential diagnosis. The purpose of this retrospective study was to critically examine both established and suggested differences between the patient groups. A total of 53 FTLB patients and 200 OT patients were included. Several findings from the current literature were replicated in this study: Compared to patients with OTs, patients with FTLB had significantly more complex tics, were older at symptom onset, were more likely to be female, and were less likely to have family members with tics. Furthermore, the study also revealed new differences between the groups: Patients with FTLB had significantly more family members with a psychiatric disorder, were more likely to have experienced an adverse psychosocial event immediately before symptom onset, and had significantly fewer simple tics. Finally, this study was unable to replicate the previously found differences in comorbidities between patients with OTs and FTLB. These findings could contribute significantly to the understanding of FTLB's etiology and to improve diagnosis, as including the presence of simple tics and comorbidities in the diagnostic criteria might be discussed in future studies.

Fine Motor Skills in Children with Tourette Syndrome and their Unaffected First-degree Siblings.

Background: The exact etiology of Tourette Syndrome (TS) remains unclear, making the search for impaired neuropsychological functions possibly connected to the underlying cause of TS as important as it is challenging. One neuropsychological domain of interest is fine motor skills. Method: This study compared fine motor skill performance on the Purdue Pegboard Task (PPT) in 18 children with TS, 24 unaffected first-degree siblings and 20 controls. A set of screening questionnaires was administered to determine comorbid psychiatric illness. Results: Children with TS, their siblings and controls did not differ significantly in fine motor skills as measured with the PPT. Performance on the PPT was not correlated with tic severity; however, we found an inverse correlation with severity of attention-deficit/hyperactivity disorder (ADHD) symptoms, as assessed by parent reported ADHD symptoms. Children with TS were found to have significantly higher parent reported ADHD symptoms compared to controls, yet only two out of the 18 participants had been diagnosed with ADHD. Conclusion: This study suggests that fine motor skill impairment in children with TS may be more strongly correlated with comorbid ADHD than to TS and tics.