Gilles de la Tourette syndrome as a rare co-morbidity of Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (47, XXY) is the most common sex chromosome aneuploidy. In addition to male hypergonadotropic hypogonadism, a wide range of neurodevelopmental disorders, anxiety and affective symptoms have been reported in a substantial proportion of cases. CASE DESCRIPTION: We document the rare case of a 43-year-old man diagnosed with Klinefelter syndrome and co-morbid Gilles de la Tourette syndrome. He presented with multiple motor and vocal tics since adolescence, as well as anxiety and affective symptoms as his main tic-exacerbating factors. Tic severity was rated as marked (Yale Global Tic Severity Scale score of 78/100), and recommendations for the treatment of both tics and psychiatric co-morbidities were formulated. DISCUSSION: Neurodevelopmental tics in the context of Klinefelter syndrome have been previously documented in three cases only. Gilles de la Tourette syndrome is 3-4 times more common in males than females and its etiological factors include multiple genetic components (genetic heterogeneity). Our case report widens the spectrum of neurodevelopmental disorders observed in the context of Klinefelter syndrome and contributes to genetic research on the role of the X chromosome in the pathophysiology of tic disorders.

Tics emergencies and malignant tourette syndrome: Assessment and management.

Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the presence of tics, frequently accompanied by a variety of neuropsychiatric comorbidities. A subset of patients with TS present with severe and disabling symptoms, requiring prompt therapeutic intervention. Some of these manifestations may result in medical emergencies when severe motor or phonic tics lead to damage of anatomical structures closely related to the tic. Examples include myelopathy or radiculopathy following severe neck ("whiplash") jerks or a variety of self-inflicted injuries. In addition to self-aggression or, less commonly, allo-aggression, some patients exhibit highly inappropriate behavior, suicidal tendencies, and rage attacks which increase the burden of the disease and are important components of "malignant TS". This subset of TS is frequently associated with comorbid obsessive-compulsive disorder. Therapeutic measures include intensive behavioral therapy, optimization of oral pharmacotherapy, botulinum toxin injections, and deep brain stimulation.

Co-morbid tics and stereotypies: a systematic literature review.

BACKGROUND: Tics and stereotypies are childhood-onset repetitive behaviours that can pose significant diagnostic challenges in clinical practice. Both tics and stereotypies are characterised by a complex co-morbidity profile, however little is known about the co-occurrence of these hyperkinetic disorders in the same patient population. OBJECTIVE: This review aimed to assess the relationship between tics and stereotypies when these conditions present in co-morbidity. METHODS: We conducted a systematic literature review of original studies on co-morbid tics and stereotypies, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Our literature search identified six studies of suitable sample size (n ≥ 40) presenting data on the association between tics and stereotypies in otherwise typically developing patients. A considerable proportion (23%) of patients diagnosed with stereotypic movement disorder present with co-morbid tics (range 18-43%). Likewise, the prevalence of primary stereotypies is increased in patients with tic disorders such as Tourette syndrome (8%, range 6-12%). DISCUSSION: Tics and stereotypies can often develop in co-morbidity. The association of tics and stereotypies in the same patient has practical implications, in consideration of the different treatment approaches. Future research should focus on the assessment and management of both conditions, particularly in special populations (e.g. patients with pervasive developmental disorders).

Functional tics: Expanding the phenotypes of functional movement disorders?

BACKGROUND AND PURPOSE: Until the outbreak reported during the COVID-19 pandemic, functional tics were considered to be a relatively rare clinical phenotype, as opposed to other functional movement disorders such as functional tremor and dystonia. To better characterize this phenotype, we compared the demographic and clinical characteristics of patients who developed functional tics during the pandemic and those of patients with other functional movement disorders. METHODS: Data from 110 patients were collected at the same neuropsychiatry centre: 66 consecutive patients who developed functional tics without other functional motor symptoms or neurodevelopmental tics and 44 patients with a mix of functional dystonia, tremor, gait, and myoclonus. RESULTS: Both groups were characterized by female sex preponderance (70%-80%) and (sub)acute onset of functional symptoms (~80%). However, patients with functional tics had a significantly earlier age at onset of functional symptoms (21 vs. 39 years). Exposure to relevant social media content was reported by almost half of the patients with functional tics, but by none of the patients with other functional movement disorders. Comorbidity profiles were similar, with relatively high rates of anxiety/affective symptoms and other functional neurological symptoms (nonepileptic attacks). CONCLUSIONS: Patients who developed functional tics during the pandemic represent a phenotypic variant of the wider group of patients with functional movement disorders, associated with younger age at onset and influenced by pandemic-related factors, including increased exposure to specific social media content. Diagnostic protocols and treatment interventions should be tailored to address the specific features of this newly defined phenotype.

Neurodevelopmental versus functional tics: A controlled study.

BACKGROUND: An unprecedented increase in newly developed functional tics, mainly in young females, has been reported during the COVID-19 pandemic. We set out to complement existing case series with the largest controlled study to date on the clinical phenomenology of functional tics versus neurodevelopmental tics. METHODS: Data from 166 patients were collected at a specialist clinic for tic disorders during a three-year period overlapping with the COVID-19 pandemic (2020-2023). We compared the clinical features of patients who developed functional tics during the COVID-19 pandemic (N = 83) to patients with Tourette syndrome matched for age and gender (N = 83). RESULTS: Female adolescents and young adults accounted for 86% of the clinical sample of patients with functional tics, who were less likely to report a family history of tic disorders than their matched controls with Tourette syndrome. Co-morbidity profiles were significantly different: anxiety and other functional neurological disorders were more strongly associated with functional tics, whereas attention-deficit and hyperactivity disorder and tic-related obsessive-compulsive behaviors co-occurred more frequently with neurodevelopmental tics. Overall, absence of tic-related obsessive-compulsive behaviors (t = 8.096; p < 0.001) and absence of a family history of tics (t = 5.111; p < 0.001) were the strongest predictors of the diagnosis of functional tics. Compared to neurodevelopmental tics, functional tics were more likely to present acutely/subacutely at a later age (21 versus 7 years), without a clear rostro-caudal progression. Coprophenomena, self-injurious behaviors, and complex clinical manifestations such as blocking tics, throwing tics, and tic attacks, were all over-represented in the functional group. CONCLUSIONS: Our findings provide robust confirmation of both patient-related variables and tic characteristics contributing to the differential diagnosis between functional tics developed during the pandemic and neurodevelopmental tics reported by patients with Tourette syndrome.

Compulsive sexual behavior and paraphilic interests in adults with chronic tic disorders and Tourette syndrome: a survey-based study.

Early research suggested that compulsive sexual behavior (CSB) and paraphilic interests (PI) are more prevalent in adults with primary tic disorders compared to the general population. However, recent data on this topic remain scarce. We conducted an anonymous online survey capturing data on CSB and PI in adult patients with primary tic disorders. We also explored the role of antipsychotic tic medication and the impact of neuropsychiatric comorbidities like attention-deficit hyperactivity disorder and depression. In total, 62 participants (26 females/36 males) completed the survey. The prevalence of CSB and PI were 12.9% and 19.4%, respectively. There was no association with antipsychotic medication nor with symptoms of depression. However, the presence of attention-deficit hyperactivity disorder was associated with a higher prevalence of both CSB and PI. The current results contrast with earlier reports and show that in adults with primary tic disorders, the prevalence of CSB and PI is not overly prominent.

Distinguishing functional from primary tics: a study of expert video assessments.

BACKGROUND: Reliably applied criteria to differentiate functional from primary tics are lacking. In the absence of biological markers, the development of new diagnostic criteria to assist clinicians is predicated on expert judgement and consensus. This study examines the level of diagnostic agreement of experts in tic disorders using video footage and clinical descriptions. METHODS: Using a two-part survey, eight experts in the diagnosis and management of tics were first asked to study 24 case videos of adults with primary tics, functional tics or both and to select a corresponding diagnosis. In the second part of the survey, additional clinical information was provided, and the diagnosis was then reconsidered. Inter-rater agreement was measured using Fleiss' kappa. In both study parts, the factors which influenced diagnostic decision-making and overall diagnostic confidence were reviewed. RESULTS: Based on phenomenology alone, the diagnostic agreement among the expert raters was only fair for the pooled diagnoses (κ=0.21) as well as specifically for functional (κ=0.26) and primary tics (κ=0.24). Additional clinical information increased overall diagnostic agreement to moderate (κ=0.51) for both functional (κ=0.6) and primary tics (κ=0.57). The main factors informing diagnosis were tic semiology, age at tic onset, presence of premonitory urges, tic suppressibility, the temporal latency between tic onset and peak severity, precipitants and tic triggers and changes in the overall phenotypic presentation. CONCLUSIONS: This study confirmed that in the absence of clinical information, the diagnostic distinction between primary and functional tics is often difficult, even for expert clinicians.

The Western origins of mindfulness therapy in ancient Rome.

Stoic philosophy has multiple parallels with cognitive behavioural therapy interventions. In their ancient texts, the Roman Stoics present a set of theoretical principles and behavioural strategies that are directly relevant to the clinical care of patients with a wide range of neuropsychiatric conditions. Mindfulness is a key component of the 'third wave' of modern psychotherapy that closely resembles the ancient Stoic practice of attention or 'concentration on the present moment'. Stoic mindfulness draws attention to one of the main principles driving both Stoicism and modern psychotherapy: the assumption that cognitive activity (reasoning) mediates emotions and behaviours. This principle can be traced back to Epictetus' Enchiridion, where he recognises that 'men are disturbed not by things, but by the views which they take of things'. It has been shown that cognitive behavioural therapies and mindfulness-based interventions directed at patients with neuropsychiatric disorders were originally developed as Stoic-inspired treatment interventions. Both Albert Ellis and Aaron Beck (the founders of rational emotive behaviour therapy and cognitive behavioural therapy, respectively) explicitly acknowledged the role of Stoicism as the philosophical precursor of their treatment approaches. The effective implementation of evidence-based guidelines would benefit from an increased awareness of the influence of the Stoic tradition of philosophical therapy on the treatment approaches currently in use in neuropsychiatry.

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.

Can Stoicism inspire stuttering intervention? The clinical usefulness of an ancient philosophy.

BACKGROUND: A range of psychotherapies are effective in managing an individual's personal reactions to stuttering and reducing the impact stuttering has on their lives. Many of these therapies, such as cognitive behavioural therapy, have their origins in Stoicism, an ancient Greek philosophy founded in 301 bce. Stoicism remains a relatively unexplored topic in the psychotherapy and speech and language therapy literatures. AIMS: This paper aims to highlight the potential benefits of integrating Stoic principles and techniques into stuttering intervention. METHODS: This aim is achieved through a discussion on Stoic philosophy and the range of techniques that have informed modern evidence-based psychotherapies that are effective with the stuttering population. MAIN CONTRIBUTION: This paper initiates an important conversation on the usefulness of Stoicism to the field of stuttering. Key recommendations are provided for the integration of Stoic philosophy into future clinical and research practice related to stuttering. CONCLUSIONS: Stoicism offers philosophical guidance for the art of living, but also provides a range of strategies and practical techniques that have potential to expand the clinical toolkit of modern psychotherapy and speech and language therapy. Scientific validation of the clinical application of Stoicism is recommended to exploit its effectiveness with the stuttering population. WHAT THIS PAPER ADDS: What is already known on the subject Stoicism is an ancient philosophy that has informed modern-day psychotherapies including cognitive behavioural therapy (CBT) and acceptance and commitment therapy (ACT). Such therapies are recommended for use with individuals who stutter to target their personal reactions to stuttering and reduce any adverse impacts on their lives. What this paper adds to existing knowledge This paper discusses the principles and techniques of Stoicism with reference to how they align with modern psychotherapeutic approaches and speech and language therapy interventions used with individuals who stutter. Clinical implications and directions for future research are also presented. What are the potential or actual clinical implications of this work? Speech and language therapists (SLTs) are recommended to continue their use of psychotherapies such as CBT and ACT with individuals who stutter. In addition, SLTs are advised to explore Stoicism and its range of techniques to better understand the philosophical underpinnings of evidence-based psychotherapies and to expand their clinical toolkit.

Current and emerging pharmacotherapeutic strategies for Tourette syndrome.

INTRODUCTION: Tourette syndrome (TS) is a chronic tic disorder characterized by both motor and vocal tics. The vast majority of patients present with co-morbid behavioral problems, especially tic-related obsessive-compulsive behaviors and attention-deficit and hyperactivity disorder. Evidence-based guidelines on the pharmacotherapy of TS have become available in recent years. AREAS COVERED: The main purpose of this paper is to provide an overview of the current and emerging pharmacotherapeutic strategies for TS. A comprehensive search for the literature on the pharmacotherapy of tics was conducted using multiple databases (MEDLINE, Scopus, Web of Science, and Google Scholar), without date limits. EXPERT OPINION: In consideration of the heterogeneity of the TS phenotypes, pharmacotherapy should be tailored to the individual patient. The choice of the pharmacological agent should take into account both the efficacy-to-tolerability ratio and the presence of co-morbid conditions. Evidence-based pharmacotherapy should aim at improving health-related quality life within a dynamic framework that typically requires active monitoring of the clinical presentation and reevaluation of the treatment intervention over time.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part IV: deep brain stimulation.

In 2011 the European Society for the Study of Tourette Syndrome (ESSTS) published its first European clinical guidelines for the treatment of Tourette Syndrome (TS) with part IV on deep brain stimulation (DBS). Here, we present a revised version of these guidelines with updated recommendations based on the current literature covering the last decade as well as a survey among ESSTS experts. Currently, data from the International Tourette DBS Registry and Database, two meta-analyses, and eight randomized controlled trials (RCTs) are available. Interpretation of outcomes is limited by small sample sizes and short follow-up periods. Compared to open uncontrolled case studies, RCTs report less favorable outcomes with conflicting results. This could be related to several different aspects including methodological issues, but also substantial placebo effects. These guidelines, therefore, not only present currently available data from open and controlled studies, but also include expert knowledge. Although the overall database has increased in size since 2011, definite conclusions regarding the efficacy and tolerability of DBS in TS are still open to debate. Therefore, we continue to consider DBS for TS as an experimental treatment that should be used only in carefully selected, severely affected and otherwise treatment-resistant patients.

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.

Is Tourette syndrome a rare condition?

Based on its prevalence, Tourette syndrome cannot be considered a rare disease. However, in this opinion article, we make the claim that it should nonetheless be considered as an orphan or neglected disease.

Aggression Toward Others Misdiagnosed as Primary Tics.

BACKGROUND: Tics describe a wide range of sudden and repetitive behaviors. Their multifaceted clinical features may resemble other explosive behaviors, including repetitive episodes of aggression toward others (allo-aggression) reported by subjects without tics. Here, we document 3 exemplary cases that help disentangle allo-aggressive behaviors from tics. CASES: We report 3 cases who presented with an array of complex repetitive behaviors, most notably allo-aggression (eg, sudden kicking, hitting, slapping and biting others, or pushing someone off a bike), which were misdiagnosed as primary tics. In all cases, additional symptoms, such as blackouts, feeling of being controlled by different personalities, or being empowered by repetitive behaviors, and examination pointed toward different neuropsychiatric diagnoses. CONCLUSIONS: Repetitive allo-aggressive behaviors are not part of the range of motor manifestations of tics. This observation not only has important medico-legal implications but is also relevant for the overall perception of Tourette syndrome and other primary tic disorders.

Aripiprazole for the treatment of Tourette syndrome.

Introduction: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple tics which often persisting in forms of different severity throughout adult life. The prevalence of neuropsychiatric co-morbidity in patients with TS is high. Treatment of TS can involve pharmacological, behavioral, or, in rare cases, surgical therapies. Over the last two decades there has been growing interest in the use of aripiprazole, a novel partial dopamine receptor agonist, as a promising anti-tic agent.Areas covered: The authors reviewed the available literature evaluating the role of aripiprazole in the treatment of TS and other tic disorders in both children and adults. This includes data from five randomized controlled trials (RCTs) and eleven open-label studies.Expert opinion: There is moderate quality evidence supporting the use of aripiprazole in reducing tic severity in children and adolescents, however there is a lack of robust evidence evaluating its use in adults, despite expert consensus. Overall, it appears that aripiprazole is a safe and effective treatment for tics. Further large scale RCTs assessing the long-term efficacy and safety of aripiprazole in the treatment of tics are warranted, especially in adult populations with TS.

Tics in patients with encephalitis.

BACKGROUND: Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in cases of encephalitis resulting from a range of aetiologies. OBJECTIVE: This review aimed to assess the prevalence and characteristics of tics in patients with encephalitis. METHODS: We conducted a systematic literature review of original studies on the major scientific databases, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: In addition to the established association between tics and encephalitis lethargica, our literature search identified reports of tics in patients with immune-mediated pathologies (including autoimmune encephalitides affecting the N-methyl-D-aspartate receptor, voltage-gated potassium channels, and glycine receptors) and infective processes (ranging from relatively common viral pathogens, such as herpes simplex, to prions, as in Creutzfeldt-Jakob disease). Tics were most commonly reported in the post-encephalitic period and involvement of the basal ganglia was frequently observed. DISCUSSION: The association of new-onset tics and encephalitis, in the background of other neuropsychiatric abnormalities, has practical implications, potentially improving the detection of encephalitis based on clinical features. Future research should focus on the categorisation and treatment of hyperkinetic movement disorders associated with encephalitis.

Possible tics diagnosed as stereotypies in patients with severe autism spectrum disorder: a video-based evaluation.

BACKGROUND: The association of stereotypies and tics is not rare in children with severe autism spectrum disorder (ASD). The differential diagnosis between stereotypies and tics in this patient population can be difficult; however, it could be clinically relevant because of treatment implications. METHODS: A total of 108 video recordings of repetitive behaviors in young patients with stereotypies in the context of ASD were reviewed by a movement disorders expert and a trainee, in order to assess the prevalence of possible co-morbid tics. The Modified Rush Videotape Rating Scale (MRVS) was used to rate tic frequency and severity. RESULTS: Out of 27 patients with stereotypies (24 males; mean age 14 years), 18 (67%) reported possible tics. The most frequently observed tics were eye blinking, shoulder shrugging, neck bending, staring, and throat clearing. The mean MRVS score was 5, indicating mild tic severity. The only significant difference between patients with tics and patients without tics was the total number of stereotypies, which was higher in the subgroup of patients without tics (p = 0.01). CONCLUSIONS: Expert review of video-recordings of repetitive behaviors in young patients with ASD and stereotypies suggests the possibility of a relatively high rate of co-morbid tics. These findings need to be integrated with a comprehensive clinical assessment focusing on the diagnostic re-evaluation of heterogeneous motor manifestations.