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We performed this study to improve understanding of the relationship between functional tic-like behaviors (FTLBs) and quality of life, loneliness, family functioning, anxiety, depression, and suicidality. This cross-sectional study assessed self-reported quality of life, disability, loneliness, depression, anxiety, family functioning, tic severity, and suicide risk in age- and birth-sex matched youth with FTLBs, Tourette syndrome (TS), and neurotypical controls. We performed specific subanalyses comparing individuals with FTLBs who identified as transgender/gender diverse (TGD) with cisgender individuals. Eighty-two youth participated (age range 11 to 25, 90% female at birth), including 35 with FTLBs, 22 with TS, and 25 neurotypical controls. A significantly higher proportion of participants with FTLB identified as TGD (15 of 35) than TS (two of 22) and neurotypical control (three of 25) participants. Compared with neurotypical controls, individuals with FTLBs had significantly lower quality of life, greater disability, loneliness, social phobia, anxiety symptoms, depressive symptoms, and suicidality. Compared with individuals with TS, individuals with FTLBs had more school/work absences due to tics, had more depressive symptoms, were more likely to be at high risk for suicidality, and had disability in self-care and life activity domains. There were no significant differences between cisgender and TGD participants with FTLB in any of the domains assessed. Youth with FTLB have unique health care needs and associations with anxiety, depression, sex, and gender. [ABSTRACT FROM AUTHOR]

Non-invasive brain stimulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation hold promise for inducing brain plasticity. However, their limited precision may hamper certain applications. In contrast, Transcranial Ultrasound Stimulation (TUS), known for its precision and deep brain targeting capabilities, requires further investigation to establish its efficacy in producing enduring effects for treating neurological and psychiatric disorders. To investigate the enduring effects of different pulse repetition frequencies (PRF) of TUS on motor corticospinal excitability. T1-, T2-weighted, and zero echo time magnetic resonance imaging scans were acquired from 21 neurologically healthy participants for neuronavigation, skull reconstruction, and the performance of transcranial ultrasound and thermal modelling. The effects of three different TUS PRFs (10, 100, and 1000 Hz) with a constant duty cycle of 10 % on corticospinal excitability in the primary motor cortex were assessed using TMS-induced motor evoked potentials (MEPs). Each PRF and sham condition was evaluated on separate days, with measurements taken 5-, 30-, and 60-min post-TUS. A significant decrease in MEP amplitude was observed with a PRF of 10 Hz (p = 0.007), which persisted for at least 30 min, and with a PRF of 100 Hz (p = 0.001), lasting over 60 min. However, no significant changes were found for the PRF of 1000 Hz and the sham conditions. This study highlights the significance of PRF selection in TUS and underscores its potential as a non-invasive approach to reduce corticospinal excitability, offering valuable insights for future clinical applications. • TUS holds potential for LTD-like plasticity induction. • TUS with 10 Hz PRF and 10 % DC induces MEP inhibition for at least 30 min. • TUS with 100 Hz PRF and 10 % DC induces MEP inhibition lasting over 60 min. • TUS with 1000 Hz PRF and 10 % DC does not change corticospinal excitability. [ABSTRACT FROM AUTHOR]

Tics and stereotypies are the most common pathological repetitive complex motor behaviors occurring during the neurodevelopmental period. Although they may appear transiently during development without acquiring a pathological status, when they become chronic they may be distressing, socially impairing, or even, in the case of malignant tics, potentially physically harmful. Despite a certain similarity in their phenomenology, physicians should be able to distinguish them for their different variability over time, topographical distribution, association with sensory manifestations, and relationship with environmental triggers. The complex phenomenology of tics and stereotypies is constantly enriched by the characterization of novel variants, e.g. tics triggered by auditory stimuli in association with misophonia and stereotypies associated with intense imagery activity. Their pathophysiology remains partially elusive, but both animal model and brain imaging studies confirm the involvement of all the three major loops (sensorimotor, associative and limbic) within the cortico-basal ganglia circuitry. From a management perspective, the greatest advances witnessed in the last decade involve the diffusion of behavioral strategies (e.g. habit reversal training or response interruption and redirection), including the development of protocols for telehealth on online training in order to optimise access. In the context of severe tics, e.g. in refractory Tourette syndrome, there is increasing experience with deep brain stimulation of the intralaminar thalamic nuclei or the globus pallidus internus, although more research is needed to fine tune target choice and stimulation setting definition. [ABSTRACT FROM AUTHOR]

He exhibited mild left-sided torticollis, dystonic posturing of fingers and internal rotation of the upper arm on the right (Burke-Fahn-Marsden [BFM] dystonia motor score 12). In conclusion, patients undergoing MRgFUS thalamotomy for tremor should be carefully examined for accompanying dystonia and warned about the potential risk of worsening or unmasking of dystonia despite tremor improvement. 1 Burke Fahn Marsden dystonia rating scale movement scores over time in patients undergoing MRgFUS thalamotomy. [Extracted from the article]

Background: Objective measures of physical and cognitive fatigability do not correlate with subjective Parkinson's disease (PD)-related fatigue. The relationship of subjective PD-related fatigue to tasks combining cognitive and motor effort has never been explored.Methods: Forty-four right-handed, non-demented PD patients, 22 with (PD-F) and 22 without (PD-NF) fatigue, were tested using a sensor-engineered glove on their more affected hand. Patients performed sequential opposition finger movements following a metronome at 2 Hz for 5 min (cued task), and for another minute following a 2-min rest. The same task was repeated without sustained auditory cueing. Movement time (inter-tapping interval, ITI) and rate, touch duration, percentage of correct sequences and clinical measures (motor and fatigue severity, depression, sleep impairment and apathy) were analysed.Results: In the cued task, motor performance worsened over time (significantly increased ITI and decreased movement rate on the third to fifth minute) in PD-F patients only. In the uncued task, motor performance deteriorated similarly in the two groups. PD-F and PD-NF patients differed in ITI and movement rate deterioration over time only in the cued task, independently from motor severity, depression and sleep impairment. The severity of subjective fatigue complaints significantly correlated with motor performance deterioration in the cued task.Conclusions: PD-related fatigue is associated with performance on an externally cued, attention-controlled motor task, but not with an uncued version of the same task. The finding supports a link between PD-related fatigue and attention-demanding motor tasks, proposing a model of inducible fatigue applicable to future clinical and neuroimaging research. [ABSTRACT FROM AUTHOR]

Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients’ serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease . [ABSTRACT FROM AUTHOR]

Introduction Evidence is emerging that nonmotor symptoms (NMS) such as neuropsychiatric, sensory and sleep disturbances play an important role in dystonia. Methods In this observation, 102 patients with cervical dystonia (CD) were included. We evaluated the complaints about NMS with an adapted NMS Questionnaire and motor severity measured with Unified Dystonia Rating Scale. Results 95% of CD patients experienced NMS with 36% presenting with at least seven NMS. Mean UDRS score was 5.09 points (standard deviation (SD) ± 2.64 points, range 0.5–14.0). 42% patients had additional head tremor. The total number of experienced NMS was not significantly correlated with the age of the patients and disease duration of dystonia. There was also no significant association between number of NMS and sex. The correlation between number of NMS and motor severity assessed with UDRS was weak ( r S = 0.23; p = 0.02). Conclusion The number of NMS as a whole has been shown to be a key determinant of health related quality of live in patients with Parkinson's disease and we would assume that can influence this construct in patients with dystonia, too. As 95% of our patients with focal CD present with NMS, especially loss of self-confidence, insomnia, fatigue and pain, higher awareness for NMS needs to be raised in the context of routine clinical consultations in patients with focal dystonia. [ABSTRACT FROM AUTHOR]

Abstract: Diagnosis and treatment of the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) variant of Gilles de la Tourette syndrome (GTS) and childhood-onset obsessive–compulsive disorder (OCD) are still controversial issues. Most cross-sectional studies confirm a significant association between GTS and the development of an immune response against group A β-hemolytic streptococcus (GABHS). Moreover, longitudinal retrospective studies suggest that a recent exposure to GABHS might be a risk factor for the onset of tics and obsessive–compulsive symptoms. However, further evidence from longitudinal prospective research is needed to verify whether a temporal association between GABHS infections and symptom exacerbations is a useful and reliable criterion for the diagnosis of PANDAS. In addition, preliminary results suggest that the PANDAS spectrum might be enlarged to include attention deficit/hyperactivity disorder. Although a number of immunological biomarkers have been proposed as markers of the PANDAS variant, at present, none of these has been conclusively proved useful to diagnose and monitor disease course in children with a suspicion of PANDAS. Finally, despite their empirical use in community settings, we still lack conclusive, evidence-based data regarding the usefulness of antibiotic and immunomodulatory treatments in children with PANDAS. Given the relevance of this topic for general pediatric health, additional research efforts to solve all the pending issues and the hottest points of debate are warranted. [Copyright &y& Elsevier]

Soluble adhesion molecules are overexpressed in neuroinflammatory disorders. Their synthesis parallels that of their membrane-bound counterparts, which modulate lymphocyte transmigration through the blood–brain barrier. Blood–brain barrier cellular migration may be essential in the evolution of postinfectious inflammatory central nervous system disease. The serum levels of soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E-selectin were measured in 12 children with acute disseminated encephalomyelitis and in two control groups (35 healthy and 35 affected by noninflammatory neurologic diseases) of similar age. In patients with acute disseminated encephalomyelitis, soluble E-selectin serum levels were significantly higher (median 113 ng/mL, range 54-144) than in both control groups (median 44, range 31-63, and median 58, range 43-89, respectively; one-way analysis of variance, P < 0.0001); a statistical trend for higher levels of soluble intercellular adhesion molecule−1 was observed in acute disseminated encephalomyelitis subjects, whereas soluble vascular adhesion molecule−1 titers did not differ between the three groups. The specific role played by each of these molecules in lymphocyte extravasation and the differential cytokine modulation of their expression might explain the result. Further larger studies are required including serial measurements and cerebrospinal fluid analysis. [Copyright &y& Elsevier]

Disgust is a multifaceted experience that might affect several aspects of life. Here, we reviewed research on neurological and psychiatric disorders that are characterized by abnormal disgust processing to test the hypothesis of a shared neurocognitive architecture in the representation of three disgust domains: i) personal experience of ‘core disgust’; ii) social disgust, i.e., sensitivity to others’ expressions of disgust; iii) moral disgust, i.e., sensitivity to ethical violations. Our review provides some support to the shared neurocognitive hypothesis and suggests that the insula might be the “hub” structure linking the three domains of disgust sensitivity, while other brain regions may subserve specific facets of the multidimensional experience. Our review also suggests a role of serotonin core and moral disgust, supporting “neo-sentimentalist” theories of morality, which posit a causal role of affect in moral judgment. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has necessitated the social isolation of the population and the rapid implementation of remote care for patients with neurodegenerative diseases. The objective of this study was to explore the perceived impact of confinement in patients with Parkinson's disease and document the effects of gender and living environment. We recruited two cohorts from the Canadian provinces of Québec and Alberta, which differed in the dynamics of COVID-19 spreading at the time of the study, and administered a questionnaire on the perceived effects of confinement on daily living and disease management. The data reveals that approximately half of the patients experienced a change in one or more clinical symptoms, with differences observed between gender (e.g. day-to-day changes in slowness in men, aggravated headaches in women) and geographic location (e.g. increased depression in Alberta but reduced sleep quality in Québec). Furthermore, participants identifying as women or living in Alberta implemented more frequently home or online exercise. Lastly, high levels of satisfaction with phone or video consultations did not translate into a sustained interest to pursue this mode of healthcare. This study suggests that COVID-19-related confinement affected Parkinson's disease manifestation and management. Patients also reported varying levels of interest to continue remote care. A number of differences reported in our study were seemingly related to gender and living environment. • During the COVID-19 confinement measures in Canada, we surveyed perceived symptom changes in patients living in two provinces. • We also explored differences in disease manifestation during confinement between men and women. • Depression, sleep quality and headaches were differently affected in Canadian provinces with low or high COVID-19 burden. • In general men reported fluctuations in motor symptoms (slowness and tremor), while women experienced a persistent worsening. • Patients in either province/gender were satisfied with remote consultations but hesitant to pursue telehealth in the future. [ABSTRACT FROM AUTHOR]

• Depression and anxiety provide the largest contribution to disability and decrease quality of life in AOID. • The pooled prevalence of depressive symptoms/disorders is 31.5% for cervical dystonia and 29.2% for cranial dystonia. • Major depressive disorder is more prevalent in cervical dystonia and dysthymia is more prevalent in cranial dystonia. • These prevalence estimates will aid future mechanistic and interventional studies, and the re-definition of models of care. Adult onset idiopathic dystonia (AOID) is the third most common movement disorder in adults. Co-existing depressive symptoms and disorders represent major contributors of disability and quality of life in these patients, but their prevalence remains unclear. We investigated the point prevalence of supra-clinical threshold depressive symptoms/depressive disorders in AOID in a systematic review with qualitative synthesis and meta-analysis. Our search identified 60 articles suitable for qualitative synthesis and 54 for meta-analysis. The overall pooled prevalence of either supra-clinical threshold depressive symptoms or depressive disorders was 31.5 % for cervical dystonia, 29.2 % for cranial dystonia, and 33.6 % for clinical samples with mixed forms of AOID. Major depressive disorder was more prevalent than dysthymia in cervical dystonia, whereas dysthymia was more prevalent in cranial dystonia. In cervical dystonia, the prevalence of supra-clinical threshold depressive symptoms screened by rating scales was higher than that of depressive disorders diagnosed with structured interviews. Prevalence studies using rating scales yielded higher heterogeneity. More research is warranted to standardize screening methodology and characterization of mood disorders in AOID. [ABSTRACT FROM AUTHOR]

Developmental stuttering and Tourette syndrome (TS) are common neurodevelopmental disorders. Although disfluencies may co-occur in TS, their type and frequency do not always represent pure stuttering. Conversely, core symptoms of stuttering may be accompanied by physical concomitants (PCs) that can be confused for tics. This scoping review aimed to explore the similarities and differences between stuttering and tics in terms of epidemiology, comorbidities, phenomenology, evolution, physiopathology, and treatment. We also described the nature of PCs in stuttering and disfluencies in TS. A literature search on Medline, Embase and PsycInfo was executed in March 2022. From 426 studies screened, 122 were included in the review (a majority being narrative reviews and case reports). TS and stuttering have several epidemiological, phenomenological, comorbidity, and management similarities suggesting shared risk factors and physiopathology (involving the basal ganglia and their connections with speech and motor control cortical regions). PCs in stuttering commonly involve the face (eyelids, jaw/mouth/lip movements) and sometimes the head, trunk and limbs. PCs can be present from early stages of stuttering and vary over time and within individuals. The function of PCs is unknown. Some individuals with TS have a distinct disfluency pattern, composed of a majority of typical disfluencies (mostly between-word disfluencies), and a mix of cluttering-like behaviors, complex phonic tics (e.g. speech-blocking tics, echolalia, palilalia), and rarely, atypical disfluencies. Future investigations are warranted to better understand the complex relationships between tics and stuttering and address the management of disfluencies in TS and PCs in stuttering. • Tics and stuttering have epidemiological, clinical, and management similarities. • The physiopathology involves both the basal ganglia and the dopaminergic pathway. • Physical concomitants (PCs) in stuttering are variable and often involve the face. • The occurrence of PCs during disfluencies helps differentiating them from tics. • Tourette syndrome has a distinct disfluency pattern, different from stuttering. [ABSTRACT FROM AUTHOR]

Background and aims Impaired emotional facial expressiveness is an important feature in Parkinson's disease (PD). Although there is evidence of a possible relationship between reduced facial expressiveness and altered emotion recognition or imagery in PD, it is unknown whether other aspects of the emotional processing, such as subjective emotional experience (alexithymia), might influence hypomimia in this condition. In this study wee aimed to investigate possible relationship between reduced facial expressiveness and altered emotion processing (including facial recognition and alexithymia) in patients with PD. Methods Forty PD patients and seventeen healthy controls were evaluated. Facial expressiveness was rated on video recordings, according to the UPDRS-III item 19 and using an ad hoc scale assessing static and dynamic facial expression and posed emotions. Six blind raters evaluated the patients' videos. Emotion facial recognition was tested using the Ekman Test; alexithymia was assessed using Toronto Alexithymia Scale (TAS-20). Results PD patients had a significantly reduced static and dynamic facial expressiveness and a deficit in posing happiness and surprise. They performed significantly worse than healthy controls in recognizing surprise (p = 0.03). The Ekman total score positively correlated with the global expressiveness (R^2 = 0.39, p = 0.01) and with the expressiveness of disgust (R^2 = 0.32, p = 0.01). The occurrence of alexithymia was not different between PD patients and HC; however, a significant negative correlation between the expressiveness of disgust was found for a subscore of TAS (R^2 = − .447, p = 0.007). Conclusions Reduced facial expressiveness in PD may be in part related to difficulties with emotional recognition in a context of an unimpaired subjective emotional experience. [ABSTRACT FROM AUTHOR]

Abstract: Background: Adult-onset primary dystonia is thought to be a purely motor disorder. Nevertheless, several studies provided evidence that sensory and psychiatric disturbances may contribute to the clinical spectrum of of dystonia, whereas evidence supporting cognitive impairment is still limited. Methods: A set of neuropsychological tests was administered to non depressed, non demented patients with cranial-cervical dystonia and healthy control subjects. The test battery included n-Back Task, Wechsler Memory Scale, Trail Making Test version A and B, and Wisconsin Card Sorting Test. Results: As compared with healthy control subjects of similar age, sex and socio-economic status, patients with cranial-cervical dystonia showed deficit on working memory functions revealed by n-Back task, impairment of mental control and visual reproduction subtests of Wechsler memory scale, deficit on information processing speed and set-shifting capacity revealed by Trail Making Test A and B. Conclusion: Patients with cranial-cervical dystonia may have impairment in specific cognitive domains relative to working memory, processing speed, visual motor ability and short term memory. Probably, these deficits are not dependent on the clinical expression of dystonia but might rather reflect the cortical and subcortical changes highlighted by functional and VBM imaging studies in patients with different forms of dystonia. [Copyright &y& Elsevier]

Abstract: Environmental exposures during the prenatal period, perinatal stages, and postnatal life may contribute to onset and course of Tourette syndrome (TS). Pregnancy-related noxious exposures may be more frequent in pregnancies of children who will develop TS, particularly maternal smoking and prenatal life stressors. Lower birth weight and use of forceps at delivery may be associated with tic severity in the offspring; moreover, low birth weight and maternal smoking during pregnancy may affect the risk of co-morbid attention-deficit/hyperactivity and obsessive-compulsive disorders. Group A streptococcal infections as risk-modifier for TS has not been convincingly demonstrated to date, although an interaction with stressors was suggested. The PANDAS hypothesis is currently undergoing a nosological revision. Only limited anecdotal evidence supports a link of TS to other pathogens. Nevertheless, the relationship between infections and TS may be complex. Recent data point to intrinsically altered immune regulation in TS, which might predispose to both infections and autoimmune mechanisms; however, evidence of cell-mediated and antibody-mediated autoimmunity in TS is still insufficient. Psychosocial stress remains the most important contextual factor influencing tic severity, as confirmed by prospective studies. This might in part be related to enhanced reactivity of the stress response in TS patients, the mechanisms of which need to be explored further. New studies on large prospective cohorts of patients of different age and the identification of reliable biomarkers or endophenotypes indicating early, prenatal exposure to environmental insults are needed. [Copyright &y& Elsevier]

Activation regulates the responsiveness of G-protein-coupled receptors (GPCRs) on T cells, and modifications in the activity of GPCRs characterize lymphocytes from some immune disorders such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Some lines of evidence suggest that such an effect is connected with the altered expression of some GPCRs regulatory proteins. Herein we demonstrate that phitoemagglutinin (PHA)-induced activation leads to differential expression of G-protein-coupled receptor kinase (GRK) 2, GRK3, β-arrestin-1, regulators of G-protein signalling (RGS) 2, and RGS16 and decreases responsiveness of mononuclear leukocytes (MNL) to the β-adrenergic agonist isoproterenol. Interferon beta-1a (IFNβ-1a), which is known to ameliorate the course of MS, counteracts the activation-induced effects on the expression of these GPCR regulatory proteins in MNL. Furthermore, IFNβ-1a quenches the effects of PHA on the isoproterenol-induced accumulation of cyclic AMP (cAMP). We suggest that regulation of GPCRs responsiveness may be a relevant property of IFNβ-1a in MS. [Copyright &y& Elsevier]