New-onset functional tics during the COVID-19 pandemic::Clinical characteristics of 105 cases from a single centre

Background and purpose The COVID-19 pandemic has been associated amongst other things with a sharp increase in adolescents and young adults presenting acutely with functional tics. Initial reports have suggested clinically relevant differences between functional tics and neurodevelopmental tics seen in primary tic disorders such as Tourette syndrome. We aimed to provide confirmatory findings from the largest single-centre cohort to date. Methods In the present study we present data from 105 consecutive patients who developed functional tics during a 3-year period overlapping with the COVID-19 pandemic (April 2020–March 2023). All patients underwent a comprehensive neuropsychiatric assessment at a single specialist centre for tic disorders. Results Female adolescents and young adults accounted for 69% of our sample. Functional tics had an acute/subacute onset in most cases (75% with a peak of severity within 1 month). We found a disproportionately high frequency of complex movements (81%) and vocalizations (75%). A subset of patients (23%) had a pre-existing primary tic disorder (Tourette syndrome with functional overlay). The most common psychiatric co-morbidities were anxiety (70%) and affective disorders (40%). Moreover, 41% of patients had at least one functional neurological disorder in addition to functional tics. Exposure to tic-related social media content was reported by half of the patients. Conclusions Our findings confirm substantial clinical differences between functional tics developed during the pandemic and neurodevelopmental tics. Both patient- and tic-related red flags support the differential diagnostic process and inform ongoing monitoring in the post-pandemic era

Development and validation of a disease-specific scale for the assessment of quality of life in patients with Gilles de la Tourette Syndrome: the GTS-QOL

Background. Gilles de la Tourette Syndrome (GTS) is a chronic neuropsychiatric disorder characterised by multiple motor and phonic tics and associated behavioural problems, with a serious impact on the health-related quality of life (HR-QOL) of patients. However, little is known on the perception of HR-QOL by patients with GTS, and no patient reported HR-QOL measures have been proposed for this population. Aim. The objective of this study is the development and validation of a new scale for the quantitative assessment of HR-QOL in patients with GTS. Methods. A pool of 40 potential scale items was generated based on interviews with 120 GTS outpatients, literature review, and consultation with experts. These items were administered, in the form of a questionnaire, to a sample of 192 patients attending the Tourette Clinic, National Hospital for Neurology and Neurosurgery, London, along with standardised clinical scales. Validated psychometric methods were used to develop a rating scale satisfying standard criteria for reliability and validity. Results. Response data analysis and item reduction methods led to a final 27-item GTS-specific HR-QOL scale (GTS-QOL) with four subscales, addressing the psychological, physical, obsessional, and cognitive domains, respectively. The psychometric properties of the GTS-QOL were further tested in a second sample of 136 subjects recruited through the UK-Tourette Syndrome Association. The GTS-QOL demonstrated satisfactory scaling assumptions and acceptability; both internal consistency reliability and test-retest reliability were high (Cronbach's alpha ≥0.8 and intraclass correlation coefficient ≥0.8); validity was supported by interscale correlations (range 0.5-0.7), repeated factor analysis, and correlation patterns with other rating scales and clinical variables. Conclusion. The GTS-QOL is proposed as a new disease-specific patient-reported scale for the measurement of HR-QOL in patients with GTS, taking into account the complexity of the clinical picture of GTS

Trials of pharmacological interventions for Tourette syndrome: a systematic review.

INTRODUCTION: Gilles de la Tourette Syndrome (GTS) is a childhood-onset hyperkinetic movement disorder defined by the chronic presence of multiple motor tics and at least one vocal tic and often complicated by co-morbid behavioural problems. The pharmacological treatment of GTS focuses on the modulation of monoaminergic pathways within the cortico-striato-thalamo-cortical circuitry. This paper aims to evaluate the efficacy and safety profiles of pharmacological agents used in the treatment of tics in patients with GTS, in order to provide clinicians with an evidence-based rationale for the pharmacological treatment in GTS. METHOD: In order to ascertain the best level of evidence, we conducted a systematic literature review to identify double-blind randomised controlled trials of medications in GTS populations. RESULTS: We identified a large number of pharmacological agents as potentially effective in improving tic symptoms. The alpha-2 agonist Clonidine is amongst the agents with the most favourable efficacy-versus-adverse events ratio, especially in patients with co-morbid attention-deficit hyperactivity disorder, although effect sizes vary evidence-based studies. DISCUSSION: Our results are in line with the findings of uncontrolled open-label studies. However, most trials have low statistical power due to the small sample sizes, and newer agents, such as Aripiprazole, have not been formally tested in double-blind randomised controlled trials. Further research should focus on better outcome measures, including Quality of Life instruments

Pharmacotherapeutic and Non-Pharmacological Options for Refractory and Difficult-to-Treat Seizures

It is currently estimated that about 20%–30% of adults and 10%–40% of children diagnosed with epilepsy suffer from uncontrolled or poorly controlled seizures, despite optimal medical management. In addition to its huge economic costs, treatment-refractory epilepsy has a widespread impact on patients’ health-related quality of life. The present paper focuses on the concepts of refractory and difficult-to-treat seizures and their pharmacological management. Evidence on efficacy and tolerability of rational pharmacotherapy with antiepileptic drug combinations and of non-pharmacological treatment options such as epilepsy surgery, neurostimulation, metabolic treatment and herbal remedies is reviewed. The importance of early identification of the underlying etiology of the specific epilepsy syndrome is emphasized, to inform early prognosis and therapeutic strategies

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

Overlapping Replicator Dynamics for Functional Subnetwork Identification

Abstract. Functional magnetic resonance imaging (fMRI) has been widely used for inferring brain regions that tend to work in tandem and grouping them into subnetworks. Despite that certain brain regions are known to interact with multiple subnetworks, few existing techniques support identification of subnetworks with overlaps. To address this limitation, we propose a novel approach based on replicator dynamics that facilitates detection of sparse overlapping subnetworks. We refer to our approach as overlapping replicator dynamics (RDOL). On synthetic data, we show that RDOL achieves higher accuracy in subnetwork identification than state-of-the-art methods. On real data, we demonstrate that RDOL is able to identify major functional hubs that are known to serve as communication channels between brain regions, in addition to detecting commonly observed functional subnetworks. Moreover, we illustrate that knowing the subnetwork overlaps enables inference of functional pathways, e.g. from primary sensory areas to the integration hubs