Functional Tic-like Behaviors: From the COVID-19 Pandemic to the Post-Pandemic Era.

During the COVID-19 pandemic, there have been multiple reports about an unforeseen surge in adolescents and young adults exhibiting sudden onset functional tic-like behaviors. This phenomenon has been mainly associated with the female gender and occasionally after exposure to social media content featuring similar patterns of functional tic-like behaviors. A significant portion of these individuals have been directed to specialist clinics for movement disorders with initial misdiagnoses of late-onset refractory Tourette syndrome. Distinguishing between rapid onset functional tic-like behaviors and neurodevelopmental tics as part of Tourette syndrome can be challenging; however, the differential diagnosis is facilitated by focusing on specific clinical and demographic factors, which we have explored in a systematic literature review. Compared to neurodevelopmental tics, functional tic-like behaviors typically present with a more abrupt and intense manifestation of symptoms, onset at a later age, higher prevalence among females, inability to suppress tics, coexisting anxiety and depression, and sometimes a history of exposure to social media content portraying tic-like behaviors of a similar nature. This novel manifestation of a functional neurological disorder may thus be viewed as an emerging neuropsychiatric condition potentially triggered/exacerbated by the psychosocial repercussions of the COVID-19 crisis.

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.

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.

Self-reported impact of the COVID-19 pandemic and lockdown on young patients with tic disorders: findings from a case-control study.

BACKGROUND: Little is known about the perceived impact of the COVID-19 pandemic and subsequent lockdown measures on young patients with tic disorders. Previous studies focused on clinician and parent ratings of tic severity, whereas the only international self-report data are available for adult populations. We present the first findings from a case-control study on children and adolescents with tics during lockdown in Italy. METHODS: We surveyed 49 patients aged 6-18 years and 245 matched controls with a newly developed questionnaire covering socio-demographic and clinical data, as well as lockdown-related changes to daily life activities. RESULTS: About half (53.2%) of the Italian school-age patients who took part in our survey experienced changes in tic severity during lockdown. Perceived increases in tic severity (29.8%) were reported more often than decreases (23.4%). Analogous trends were reported for perceived restlessness and, more significantly, irritability, whereas changes in pain symptoms were less common and were similar in both directions. The presence of tics was associated with increased difficulties with remote learning (p = 0.01), but decreased feelings of missing out on social interactions with schoolmates (p = 0.03). CONCLUSIONS: Self-reported data on the impact of COVID-19 lockdown in school-age patients with tic disorders indicate perceived changes in tic severity, as well as restlessness and irritability, in about half of the cases. These findings could guide both clinicians and teachers in the implementation of targeted adjustments in the delivery of care and educational strategies, respectively.

Treatment of VGKC complex antibody-associated limbic encephalitis: a systematic review.

Limbic encephalitis is an autoimmune neuropsychiatric condition characterized by subacute cognitive symptoms, seizures, and affective changes. Although limbic encephalitis is usually caused by an immune reaction secondary to neoplasms, different types of potentially treatable non-paraneoplastic limbic encephalitis (nPLE) have recently been described. In particular, published studies have reported variable responses to immunosuppressive therapy in Voltage-Gated Potassium Channel (VGKC) complex antibody-associated nPLE. This systematic literature review found that the most significant improvements were reported by patients presenting with affective symptoms and consistent neuroradiological changes. In these patients, improved clinical outcomes correlated with the largest decreases in antibody titers.

"Not just right experiences" in patients with Tourette syndrome: complex motor tics or compulsions?

Tourette syndrome (TS) is a chronic tic disorder often accompanied by specific obsessive-compulsive symptoms (OCS) or full-blown obsessive-compulsive disorder (OCD). Repetitive behaviours are commonly reported by patients with TS, who experience the urge to perform an action until it has been done "just right". This study investigated the clinical correlates of "not just right experiences" (NJREs) in this clinical population. A standardised battery of self-report psychometric measures was administered to 71 adult patients with TS recruited from a specialist TS clinic. NJREs were systematically screened for using the Not Just Right Experiences-Questionnaire Revised (NJRE-QR). The vast majority of patients in our clinical sample (n=57, 80%) reported at least one NJRE. Patients diagnosed with TS and co-morbid OCD/OCS (n=42, 59%) reported a significantly higher number of NJREs compared to TS patients without OCD/OCS. The strongest correlation was found between NJRE-QR scores and self-report measures of compulsivity. NJREs appear to be intrinsic to the clinical phenomenology of patients with TS and can present with higher frequency in the context of co-morbid OCD/OCS, suggesting they are more related to compulsions than tics.

Sensory phenomena: clinical correlates and impact on quality of life in adult patients with Tourette syndrome.

Tourette syndrome (TS) is a neurodevelopmental condition characterised by multiple tics, with frequent behavioural co-morbidity. Sensory phenomena (SP) are unpleasant sensations which provide involuntary urges to tic in patients with TS. While SP have a central role in tic expression, little is known about their clinical correlates or association with health-related quality of life (HR-QOL) in TS. We conducted a cross-sectional study on 72 adult outpatients with TS, recruited at a specialist clinic. All participants completed a comprehensive battery of psychometric measures, including the Premonitory Urges for Tics Scale (PUTS) to assess SP and a disease-specific quality of life scale (GTS-QOL) to assess HR-QOL. SP were very common (97.2% of patients), with a median PUTS total score of 28/40. Bivariate analyses showed that PUTS scores were most significantly correlated with self-report measures of vocal tic severity and compulsivity. PUTS scores were also significantly correlated with GTS-QOL scores, most notably with the psychological subscale. SP are frequently reported by adults with TS, are associated with perceived tic severity and compulsivity, and can significantly affect psychological well-being. Standardised measurement of SP should be incorporated into routine assessment of patients with TS to optimise their clinical management.

Functional neuroanatomy and behavioural correlates of the basal ganglia: evidence from lesion studies.

INTRODUCTION: The basal ganglia are interconnected with cortical areas involved in behavioural, cognitive and emotional processes, in addition to movement regulation. Little is known about which of these functions are associated with individual basal ganglia substructures. METHODS: Pubmed was searched for literature related to behavioural, cognitive and emotional symptoms associated with focal lesions to basal ganglia structures in humans. RESULTS: Six case-control studies and two case reports were identified as relevant. Lesion sites included the caudate nucleus, putamen and globus pallidus. These were associated with a spectrum of behavioural and cognitive symptoms, including abulia, poor working memory and deficits in emotional recognition. DISCUSSION: It is often difficult to precisely map associations between cognitive, emotional or behavioural functions and particular basal ganglia substructures, due to the non-specific nature of the lesions. However, evidence from lesion studies shows that most symptoms correspond with established non-motor frontal-subcortical circuits.

The pathophysiology of impulse control disorders in Parkinson disease.

AIMS: This review aims to evaluate the most recent evidence on the pathophysiology of impulse control disorders (ICDs) in Parkinson disease (PD). METHODS: Computerised searches of Medline, Embase and PsycInfo, along with manual searches for grey literature, were conducted and resulted in a total of 16 studies suitable for review. RESULTS: Evidence was divided into four categories: medication used in PD management, imaging studies, genetic analysis and subthalamic deep brain stimulation (STN-DBS). Analysis of the literature reveals that both intrinsic and extrinsic factors may play a role in the pathophysiology of ICDs in PD. Dysfunction of the mesocorticolimbic pathway and polymorphisms of the dopamine D3 and D4 receptors may increase an individual's susceptibility to the development of ICDs. DISCUSSION: Dopaminergic medication, particularly dopamine agonists (DAs), increases the risk of developing impulsive behaviours in a PD patient. Further evidence, particularly in the form of prospective studies and randomised controlled trials is required to better establish the pathophysiology of ICDs in PD.

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.

The neurobiology and treatment of restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a relatively common neurological disorder affecting sleep and health-related quality of life. Neuroimaging studies, autopsy investigations and experimental studies using animal models have been conducted to investigate the potential causes of RLS, resulting in the generation of multiple pathophysiological hypotheses. METHODS: This paper reviews the neurobiology and pharmacotherapy of RLS, with a critical analysis of the heterogeneity and methodological limitations of the existing scientific literature. RESULTS: Although several neurotransmitter systems dysfunction and neuroanatomical abnormalities have been implicated in RLS pathogenesis, dopamine dysfunction within basal ganglia pathways, iron deficiency and opioid system abnormalities have consistently been found to be involved. Their involvement is further strengthened by the therapeutic effectiveness of dopaminergic agents, iron supplementation and opioid medications. DISCUSSION: Converging evidence from neuroimaging, autoptic and animal studies points towards dopamine dysregulation and iron metabolism alterations as the main contributors to RLS pathophysiology. The possible interactions between different neurotransmitter systems should guide further neuropharmacological research in order to improve therapeutic efficacy for this disabling condition.

"Keep up the good work"! A case study of the effects of a specific cognitive training in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by significant impairment in multiple cognitive domains. In recent years, the development of cognitive trainings in AD has received significant attention. In the present case study we designed a cognitive training program (GEO, Geographical Exercises for cognitive Optimization) based on an errorless paradigm and tailored to the patient's cultural interests. The aim of this training was to investigate the potential for acquiring and possibly retaining both procedural and verbal knowledge in early-stage AD. This study involved an 80-year-old female patient diagnosed with early-stage AD, and 10 matched healthy subjects. Participants were asked to perform the two GEO training tasks: a "puzzle-like" task for procedural memory, and an "association" task for verbal memory. Both the patient and the healthy controls were subsequently trained with GEO using the same two tasks for 2 months. Although the patient's performance before training in both tasks was poor compared to healthy controls, after the training these differences disappeared. Our results showed that the patient was able to acquire new procedural abilities and verbal knowledge, and that her achievements were stable at the follow-up testing scheduled 3 months after the end of the intervention. This case study suggests a potentially useful strategy for cognitive training in AD.

Health-related quality of life in Gilles de la Tourette syndrome: a decade of research.

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental condition characterised by multiple motor and phonic tics and associated behavioural problems, carrying a significant burden on patients' lives. Although the term health related-quality of life (HR-QOL) has only been used in recent years, several studies have long addressed the impact of GTS on physical, psychological and social aspects of wellbeing of both children and adults with GTS. We set out to answer the question "Is HR-QOL affected by GTS and, if so, in what domains?" by conducting a systematic literature review of published original studies addressing HR-QOL in both children and adult patients with GTS. This review focuses on the current evidence on the impact of GTS on patients' lives, mainly informed by studies using generic functional impairment and HR-QOL measures from the last decade, and expands on the new opportunities introduced by the recently developed GTS-specific HR-QOL scales (GTS-QOL and GTS-QOL-C&A). Analysis of the first decade of studies specifically addressing HR-QOL in GTS suggests that co-morbid conditions are key factors in determining HR-QOL in young patients, whilst the picture is more complex in adults with GTS. These findings offer some general directions for both current clinical practice and future research.

Premonitory urges and sensorimotor processing in Tourette syndrome.

Most patients with Tourette syndrome report characteristic sensory experiences (premonitory urges) associated with the expression of tic symptoms. Despite the central role of these experiences to the clinical phenomenology of Tourette syndrome, little is known about their underlying brain processes. In the present article we present the results of a systematic literature review of the published studies addressing the pathophysiological mechanisms of premonitory urges. We identified some preliminary evidence for specific alterations in sensorimotor processing at both cortical and subcortical levels. A better insight into the brain correlates of premonitory urges could lead to the identification of new targets to treat the sensory initiators of tics in patients with Tourette syndrome.

Behavioural treatments for Tourette syndrome: an evidence-based review.

Tourette syndrome (TS) is a disorder characterised by multiple motor and vocal tics and is frequently associated with behavioural problems. Tics are known to be affected by internal factors such as inner tension and external factors such as the surrounding environment. A number of behavioural treatments have been suggested to treat the symptoms of TS, in addition to pharmacotherapy and surgery for the most severe cases. This review compiled all the studies investigating behavioural therapies for TS, briefly describing each technique and assessing the evidence in order to determine which of these appear to be effective. Different behavioural therapies that were used included habit reversal training (HRT), massed negative practice, supportive psychotherapy, exposure with response prevention, self-monitoring, cognitive-behavioural therapy, relaxation therapy, assertiveness training, contingency management, a tension-reduction technique and biofeedback training. Overall, HRT is the best-studied and most widely-used technique and there is sufficient experimental evidence to suggest that it is an effective treatment. Most of the other treatments, however, require further investigation to evaluate their efficacy. Specifically, evidence suggests that exposure with response prevention and self-monitoring are effective, and more research is needed to determine the therapeutic value of the other treatments. As most of the studies investigating behavioural treatments for TS are small-sample or single-case studies, larger randomised controlled trials are advocated.

Tolerability profile of clonidine in the treatment of adults with Tourette syndrome.

OBJECTIVE: Clonidine, an alpha-2 adrenergic agonist, has been used to treat Tourette syndrome (TS) for nearly 3 decades. This first-tier medication is especially recommended for children and adolescents with a combination of attention-deficit/hyperactivity disorder and mild tics. Although clonidine is thought to have a low rate of adverse effects (AEs), little is known about its tolerability profile in adult patients with TS. METHODS: This study investigated the prevalence and characteristics of AEs associated with clonidine through a retrospective chart review. We assessed 36 patients with TS (27 men; mean [SD] age, 24.6 ± 13.9; range, 10-62 years), of whom 32 (88.8%) had comorbid conditions (most common: attention-deficit/hyperactivity disorder, n = 12; obsessive-compulsive disorder, n = 9). RESULTS: Seventeen patients (47.2%) experienced AEs. Eleven patients (30.5%) withdrew clonidine because of the severity of AE (n = 5) or absence (n = 4)/reduction (n = 2) in efficacy. The most commonly reported AEs were sedation and headache. In most cases, AEs were mild and occurred with higher starting doses. In 12 patients (70.6%) who also took other psychotropic medications, cotherapy could have been linked to the appearance of AE. CONCLUSIONS: Our findings suggest that clonidine is a safe and well-tolerated medication in the TS population. Adults with TS treated with this medication experience mild and relatively infrequent AE; high starting dose and polytherapy seem to be the only clinically relevant risk factors for AE development.

The most cited works in Tourette syndrome.

The impact of scientific articles is proportional to the citations they have received. In this study, the most cited works ("citation classics") related to Tourette syndrome (TS) were identified as articles with more than 100 citations according to the Web of Science. We retrieved 89 highly cited articles, which were published in 26 journals: 54 clinical studies, 27 laboratory studies, 7 reviews, and 1 classification article. Clinical studies consisted of phenomenologic evaluations of TS and comorbid behavioral problems (n = 22) and studies on pharmacotherapy (n = 16) and clinical genetics (n = 13), whereas laboratory studies covered basic genetics, cellular and molecular biology (n = 11), and neurobiology (neuroimaging, neuropathology, and neurophysiology) (n = 16). The majority (58%) of citation classics were published after 1990, when laboratory studies (especially neuroimaging, immunologic, and genetic studies) became widely cited. These articles are able to reach the highest numbers of citations in a short time span and suggest potential directions for future research.