A meta-analysis of transcranial magnetic stimulation in Tourette syndrome.

There is growing enthusiasm for the treatment of neuropsychiatric disorders using neuromodulation. While some reports claim that transcranial magnetic stimulation (TMS) can be used to treat Tourette Syndrome (TS), little research exists to support this assertion. This meta-analysis examined the efficacy of TMS to reduce tic severity in patients with TS. Additionally, it explored the effect of TMS to reduce premonitory urge severity-the primary mechanism implicated in the frontline evidence-based treatment of TS. Five treatment comparisons were selected using PRISMA guidelines. All studies included were required to be (1) a randomized controlled trial, (2) compare TMS to a sham condition, and (3) have all participants meet diagnostic criteria for a persistent tic disorder and/or TS. A random effects model meta-analysis examined the efficacy of using TMS to reduce tic severity and explored the effect of TMS to reduce premonitory urge severity. TMS did not significantly reduce tic severity (g = 0.44; 95% CI = -0.17, 1.05; z = 1.40; p = 0.16), but a moderate reduction in premonitory urge severity was found (g = 0.63; 95% CI = 0.9, 1.17; z = 2.27; p < 0.02). Trials with larger sample sizes and a preponderance of women were found to have greater therapeutic effects of TMS for tic severity. There is limited support for the use of TMS to reduce tic severity, though reductions in premonitory urge severity were observed. Major limitations of the existing literature are examined, with a call for research investigating newer TMS protocols and their use as a treatment augmentation strategy.

The role of neuroactive steroids in tic disorders.

Tics are sudden, repetitive movements or vocalizations. Tic disorders, such as Tourette syndrome (TS), are contributed by the interplay of genetic risk factors and environmental variables, leading to abnormalities in the functioning of the cortico-striatal-thalamo-cortical (CSTC) circuitry. Various neurotransmitter systems, such as gamma-aminobutyric acid (GABA) and dopamine, are implicated in the pathophysiology of these disorders. Building on the evidence that tic disorders are predominant in males and exacerbated by stress, emerging research is focusing on the involvement of neuroactive steroids, including dehydroepiandrosterone sulfate (DHEAS) and allopregnanolone, in the ontogeny of tics and other phenotypes associated with TS. Emerging evidence indicates that DHEAS levels are significantly elevated in the plasma of TS-affected boys, and the clinical onset of this disorder coincides with the period of adrenarche, the developmental stage characterized by a surge in DHEAS synthesis. On the other hand, allopregnanolone has garnered particular attention for its potential to mediate the adverse effects of acute stress on the exacerbation of tic severity and frequency. Notably, both neurosteroids act as key modulators of GABA-A receptors, suggesting a pivotal role of these targets in the pathophysiology of various clinical manifestations of tic disorders. This review explores the potential mechanisms by which these and other neuroactive steroids may influence tic disorders and discusses the emerging therapeutic strategies that target neuroactive steroids for the management of tic disorders.

Time is ticking for TikTok tics: A retrospective follow-up study in the post-COVID-19 isolation era.

INTRODUCTION: During the COVID-19 pandemic, an influx of adolescents presented worldwide with acute onset of functional tic-like behaviors (FTLBs). Our goal was to evaluate psychosocial factors around onset, to elucidate outcomes after pandemic isolation protocols were lifted, and to examine therapy and medication management. METHODS: A retrospective review was performed of 56 patients ages 10-18 years with new-onset FTLBs seen at Boston Children's Hospital beginning in March 2020. Demographic factors, medical history, and treatment were evaluated. Patient outcomes were determined retrospectively based on the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales from follow-up visits. CGI-I scores assessed the progression of FTLBs; CGI-S assessed overall function. RESULTS: Ninety-six percent of patients were female-assigned at birth with high rates of comorbid anxiety (93%) and depression (71%). Forty-five percent were gender-diverse. Based on scales that assessed FTLBs (CGI-I) and overall functioning (CGI-S), up to 79% of patients improved independent of comorbid diagnosis or treatment. Evidence-based tic-specific treatments were not more effective than other treatments. A subset of patients had improvement in their FTLBs but not in their general functioning and continued to have other psychosomatic presentations. CONCLUSION: While many patients' FTLBs improved, it is critical to remain alert to patients' overall function and to assess for other functional neurological disorders and mental health concerns. The tendency of FTLBs to improve in this population, independent of treatment, highlights the unique pathophysiology of FTLBs. Future research on contributing psychosocial factors and specific treatment protocols will allow optimal support for these patients.

Premonitory Urge in Patients with Tics and Functional Tic-like Behaviors.

BACKGROUND: Premonitory urges (PU) are well described in primary tics, but their frequency and intensity in functional tic-like behaviors (FTLB) are unclear. OBJECTIVE: To study the experience of PU in patients with FTLB. METHODS: We compared the results of the premonitory urge for tics scale (PUTS) in adults with tics and FTLB in the University of Calgary Adult Tic Registry. RESULTS: We included 83 patients with tics and 40 with FTLB. When comparing patients with tics, FTLB with tics and FTLB only, we did not detect significant differences either in the total PUTS score (P = 0.39), or in any of the individual PUTS item sub-scores (P values ranging between 0.11 and 0.99). CONCLUSIONS: Patients with FTLB report PU at similar frequency and intensity to patients with tics. This finding confirms that PU are not a useful feature to discriminate FTLB from tics.

Functional Tic-Like Behaviors: A Common Comorbidity in Patients with Tourette Syndrome.

BACKGROUND: Comorbid functional tic-like behaviors (FTB) have been described only rarely in patients with Tourette syndrome (TS). OBJECTIVES: We present the first large sample of patients suffering from TS and FTB to raise awareness of this clinical presentation and to guide how to differentiate one from the other. METHODS: We analyzed clinical data of 71 patients (n = 27 [38.0%] female, mean age: 21.5, range: 11-55) with TS + FTB. RESULTS: In the majority of patients, FTB started abruptly on average 15 years after tic onset with "treatment-resistant" complex movements and ("coprophenomena-like") vocalizations preceded by timely related psychological stressors. Psychological evaluation revealed evidence for internal conflicts (79%), emotional dysregulation (56%), and maintaining factors (70%). About one third of patients had a positive history for further medically unexplained symptoms. Compared to a large TS sample (n = 1032), patients with TS + FTB were more likely to be female, and presented significantly more common with "coprophenomena-like" symptoms, atypical influential factors, atypical descriptions of premonitory sensations, and higher rates of comorbid obsessive-compulsive disorder and "self-injurious" behavior. CONCLUSIONS: Based on our data it can be assumed that FTB is a common comorbidity in TS, similar to functional overlay in other movement disorders and epilepsy. Before classifying a patient as suffering from treatment-resistant TS, FTB should be ruled out.

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

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.

Treating Tourette Together: An Agenda for Patient-Centered Research Focused on Comprehensive Behavioral Intervention for Tics.

To establish a patient-centered agenda for research that will lead to effective, widespread availability, adoption, and utilization of evidence-based behavioral treatment of Tourette syndrome and other tic disorders (TDs), we planned and executed a multistage, collaborative "Treating Tourette Together" research planning project with researchers, clinicians, patients, families, and other interested parties. Priorities for future behavioral treatment research were solicited from these parties via anonymous community surveys, a 2-day research planning summit with 46 individuals representing key stakeholder groups, and community response to summit reports. Four high-priority research domains were identified: (a) expanding treatment access, (b) improving treatment outcomes, (c) optimizing treatment within a broader care model, and (d) evaluating outcomes beyond tic severity. Community-engaged participatory research models can efficiently delineate clear and actionable priorities for clinical research. This approach holds promise for improving the impact of clinical research in TDs and other neuropsychiatric disorders.

Efficacy of differential reinforcement of other behaviors therapy for tic disorder: a meta-analysis.

INTRODUCTION: Recently, studies on behavioral tic suppression techniques have gained popularity as opposed to pharmacological alternatives that often have potentially dangerous side effects. Differential Reinforcement of Other Behaviors therapy (DRO) is one such behavioral technique whose efficacy in tic suppression has been experimentally demonstrated albeit in studies with very few patients, and lacking statistical power. Here, we conducted a meta-analysis of these studies to improve their overall power and explore whether DRO intervention is really effective for tic suppression. MATERIALS AND METHODS: PubMed, Embase, PsycINFO, and Cochrane Library were searched from inception to August 30, 2023. Only original interventional studies that examined the efficacy of DRO for tic suppression were included. RESULTS: A total of 8 no control interventional studies involving 79 children with tic disorders were recruited. Most of the children had moderate tic severity. The pooled mean Yale Global Tic Severity Scale (YGTSS) score was 24.64 (95% CI: 21.99 - 30.12, p = < 0.00001, I2 = 87%). In terms of efficacy of the DRO technique for tic suppression, the results showed that DRO was effective in reducing tic frequency among the children. The pooled standardized mean difference (SMD) was -10.25 (95% CI: -14.71 - -5.79, p = < 0.00001) with I2 = 94%. CONCLUSION: In conclusion, this study revealed that DRO is potentially an effective tic suppression technique for temporarily managing tic disorder. It also showed that DRO could be employed for both moderate and severe tic disorders. However, the technique bears crucial limitations that limit its implementation outside of experimental settings. More studies are needed to address these limitations and improve its applicability in the real world.

Tic disorder in allergic rhinitis children and adolescents: a case-control study.

BACKGROUND: Allergic rhinitis is the most common allergic disease. It can accompany psychological disorders such as tic disorders due to the prolonged course of the symptoms of allergic rhinitis. This pioneer case-control study aims to investigate tic disorders in children and adolescents under 18 years of age diagnosed with allergic rhinitis. METHOD: The case group in this study consisted of patients who had both allergic rhinitis and tic disorders. Patients with allergic rhinitis without tic disorders were also enrolled as the control group with matched gender and age. Demographic characteristics, tic classifications, and contributing factors for allergic rhinitis and tic disorders were studied among the cases. Tic disorders were evaluated using DSM-5 criteria for the classification of tic disorders. RESULTS: 47 patients in the case group and 47 patients in the control group were included in this study. 53.2% and 46.8% were males and females in the case group, respectively. The mean age of the patients was 10.46 ± 3.97 years old. Sound tics were more common among the patients compared to motor tics. Patients with concomitant AR and tic disorders had more days per week with AR symptoms (P-value ≤ 0.001; OR (every day vs. three days a week = 11.02(2.98, 40.76))). Most patients with sound tick were women (p: 0.026), and most patients with motion tic were in the Provisional tic disorder group (p: 0.001). The history of infantile eczema was seen more in patients without sound tic (p: 0.025), and otitis media was significantly less common among patients with sound tics (p: 0.026). Provisional tic disorder was the most common class among the patients. In the case group (coexistence between allergic rhinitis and tic) compared to the control group, patients had significantly more days with AR symptoms per week. CONCLUSION: This preliminary study indicates that Provisional tic disorder was the most common classification of tic among patients with allergic rhinitis, especially in patients with motor tics. Asthma in motor tics, a history of food allergy in infancy, and a history of infantile eczema were also common among patients with vocal tics. Also, patients with allergic rhinitis and tic had more severe disease (more symptoms per week) than those with rhinitis alone. These findings emphasize the association of tic disorders with immunological pathways.

Rethinking Movement Disorders.

At present, clinical practice and research in movement disorders (MDs) focus on the "normalization" of altered movements. In this review, rather than concentrating on problems and burdens people with MDs undoubtedly have, we highlight their hidden potentials. Starting with current definitions of Parkinson's disease (PD), dystonia, chorea, and tics, we outline that solely conceiving these phenomena as signs of dysfunction falls short of their complex nature comprising both problems and potentials. Such potentials can be traced and understood in light of well-established cognitive neuroscience frameworks, particularly ideomotor principles, and their influential modern derivatives. Using these frameworks, the wealth of data on altered perception-action integration in the different MDs can be explained and systematized using the mechanism-oriented concept of perception-action binding. According to this concept, MDs can be understood as phenomena requiring and fostering flexible modifications of perception-action associations. Consequently, although conceived as being caught in a (trough) state of deficits, given their high flexibility, people with MDs also have high potential to switch to (adaptive) peak activity that can be conceptualized as hidden potentials. Currently, clinical practice and research in MDs are concerned with deficits and thus the "deep and wide troughs," whereas "scattered narrow peaks" reflecting hidden potentials are neglected. To better delineate and utilize the latter to alleviate the burden of affected people, and destigmatize their conditions, we suggest some measures, including computational modeling combined with neurophysiological methods and tailored treatment. © 2024 International Parkinson and Movement Disorder Society.

An investigation into mothers' experiences of their children's functional tic-like behaviour and tic attacks.

OBJECTIVE: This is the first study to systematically explore the lived experiences of sudden and new onset of severe functional tics from the perspective of the mother's experiences and describes their attempts to access support services in the United Kingdom. METHOD: Twenty-One mothers of young people aged between 12 to 17 years with functional tic-like behaviour (FTLB) took part in semi-structured interviews. Thematic analysis of the transcribed interviews revealed gaps and inconsistencies within the process of gaining access to professional services and a lack of support for the management of tics and functional tic-like movements, in addition to highlighting the impact it had on daily family life. RESULTS: The themes generated included the occurrence and development of tics, the severity and intensity of symptoms, the psychological impact on the family and the need to make recommendations for a clear care pathway. Managing the impact of the FTLB and co-occurring conditions such as suicidal ideation and self-harm, as well as the physical and emotional trauma, commonly contributed to feelings of isolation and helplessness, which impacted negatively on the family's ability to function and participate in society. CONCLUSIONS: The findings emphasize the urgent need to create a clear management pathway for those experiencing FTLB, including the need for more professionals with relevant knowledge, to improve the dialogue with families during the referral process, whilst prioritising the treatment of anxiety and other identified mental health concerns.

Parent-Report Sleep Disturbances and Everyday Executive Functioning Difficulties in Children with Tourette Syndrome.

There is an increasing need to identify and treat sleep disturbances in Tourette syndrome (TS), a neurodevelopmental condition characterized by tics. This study explored sleep, tics, and executive functioning in children with TS (n=136) and neurotypical controls (n=101) through parent-report scales and open-ended questions. 85% of children with TS scored in the clinical range for a sleep disorder. Higher tic severity predicted increased sleep disturbances and executive difficulties. Qualitative insights indicated a bidirectional link between sleep and tics, which warrants consideration in clinical settings. Further research is needed to explore causal links.

Microlesion Effect Induced by Electrode Implantation in the Posteroventral Globus Pallidus Interna for Severe Dystonic Tics.

Background: Tourette syndrome (TS) is a neurologic condition characterized by motor and phonic tics. Dystonic tics, including blepharospasm, are considered atypical or unusual in severe TS. Case Report: We report a severe case of TS with facial dystonic tics resembling blepharospasm in which the microlesion effect and a sustained therapeutic effect was observed with bilateral globus pallidus interna (GPi) deep brain stimulation (DBS). Discussion: Bilateral GPi DBS can be beneficial for blepharospasm-like tics and severe symptoms of TS. The improvements seen can be explained by the microlesion effect induced by DBS lead placement in the GPi.

What are the Key Phenomenological Clues to Diagnose Functional Tic-Like Behaviors in the Pandemic Era?

BACKGROUND: Functional tic-like behaviors (FTLBs) can be difficult to distinguish from tics. OBJECTIVES: To describe the phenomenology of FTLBs in youth and assess the movements and vocalizations most suggestive of the diagnosis. METHODS: We compared the phenomenology of tics between youth (<20 yr) with FTLBs and with primary tics from our Registry in Calgary, Canada. RESULTS: Two hundred and thirty-six youths were included: 195 with primary tics (75% males; mean age: 10.8 yr) and 41 with FTLBs (98% females; 16.1 yr). In the bivariate models, FTLBs were most associated with copropraxia (OR = 15.5), saying words (OR = 14.5), coprolalia (OR = 13.1), popping (OR = 11.0), whistling (OR = 9.8), simple head movements (OR = 8.6), and self-injurious behaviors (OR = 6.9). In the multivariable model, FTLBs were still associated with saying words (OR = 13.5) and simple head movements (OR = 6.3). Only 12.2% of youth with FTLBs had throat clearing tics (OR = 0.2). CONCLUSIONS: This study shall help physicians diagnose youth with FTLBs according to the presence/association of specific movements and vocalizations.

Mapping Gilles de la Tourette syndrome through the distress and relief associated with tic-related behaviors: an fMRI study.

Personal distress associated with tic urges or inhibition and relief associated with tic production are defining features of the personal experience in Gilles de la Tourette syndrome (GTS). These affective phenomena have not been studied using fMRI, hindering our understanding of GTS pathophysiology and possible treatments. Here, we present a novel cross-sectional fMRI study designed to map tic-related phenomenology using distress and relief as predicting variables. We adopted a mental imagery approach and dissected the brain activity associated with different phases of tic behaviors, premonitory urges, and the ensuing tic execution or inhibition: these were compared with the mental simulation of "relaxed situations" and pre-determined stereotyped motor behaviors. We then explored whether the ensuing brain patterns correlated with the distress or relief perceived for the different phases of the tasks. Patients experienced a higher level of distress during the imagery of tic-triggering scenarios and no relief during tic inhibition. On the other hand, patients experienced significant relief during tic imagery. Distress during tic-triggering scenarios and relief during tic imagery were significantly correlated. The distress perceived during urges correlated with increased activation in cortical sensorimotor areas, suggesting a motor alarm. Conversely, relief during tic execution was positively associated with the activity of a subcortical network. The activity of the putamen was associated with both distress during urges and relief during tic execution. These findings highlight the importance of assessing the affective component of tic-related phenomenology. Subcortical structures may be causally involved in the affective component of tic pathophysiology, with the putamen playing a central role in both tic urge and generation. We believe that our results can be readily translated into clinical practice for the development of personalized treatment plans tailored to each patient's unique needs.

Impact of movie and video game elements on tic manifestation in children.

BACKGROUND AND PURPOSE: Children in developed countries spend a significant portion of their waking hours engaging with audiovisual content and video games. The impact of media consumption on children's health and well-being has been widely studied, including its effects on tic disorders. Previous studies have shown that tic frequency can both increase and decrease during activities like gaming and television watching, resulting in mixed findings. METHODS: To better understand the impact of audiovisual media on tics, we conducted a fine-grained tic manifestation analysis. We focused on the effects of the impact of a movie scene with suspensful elements and a video game designed to heighten anticipation, thought to stimulate phasic and striatal dopamine release. We closely monitored tic frequency throuhghout these experiences based on moment-to-moment tic annotation. The study included 20 participants (19 males aged 7-16) diagnosed with tic disorders (Yale Global Tic Severity Scale≥8), and we tested the replicability of our findings with an independent group of 36 children (15 females, aged 7-15) with tic disorders. RESULTS: During film viewing, we observed significant synchronization in the temporal tic patterns of various individuals despite diversity in their tic profiles. Furthermore, employing a video game developed for our study, we found that tic frequency increases during anticipation of a pending reward. This finding was replicated in a second experiment with an independent cohort. CONCLUSIONS: Our results indicate that tic frequency is affected by media elements in the short-term, and call for further investigation of the long-term impacts of exposure to such tic triggers.