Rapid Compensation for Noisy Voluntary Movements in Adults with Primary Tic Disorders.

BACKGROUND: It has been proposed that tics and premonitory urges in primary tic disorders (PTD), like Tourette syndrome, are a manifestation of sensorimotor noise. However, patients with tics show no obvious movement imprecision in everyday life. One reason could be that patients have strategies to compensate for noise that disrupts performance (ie, noise that is task-relevant). OBJECTIVES: Our goal was to unmask effects of elevated sensorimotor noise on the variability of voluntary movements in patients with PTD. METHODS: We tested 30 adult patients with PTD (23 male) and 30 matched controls in a reaching task designed to unmask latent noise. Subjects reached to targets whose shape allowed for variability either in movement direction or extent. This enabled us to decompose variability into task-relevant versus less task-relevant components, where the latter should be less affected by compensatory strategies than the former. In alternating blocks, the task-relevant target dimension switched, allowing us to explore the temporal dynamics with which participants adjusted movement variability to changes in task demands. RESULTS: Both groups accurately reached to targets, and adjusted movement precision based on target shape. However, when task-relevant dimensions of the target changed, patients initially produced movements that were more variable than controls, before regaining precision after several reaches. This effect persisted across repeated changes in the task-relevant dimension across the experiment, and therefore did not reflect an effect of novelty, or differences in learning. CONCLUSIONS: Our results suggest that patients with PTD generate noisier voluntary movements compared with controls, but rapidly compensate according to current task demands. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Lesion network of oculogyric crises maps to brain dopaminergic transcriptomic signature.

Oculogyric crises are acute episodes of sustained, typically upward, conjugate deviation of the eyes. Oculogyric crises usually occur as the result of acute D2-dopamine receptor blockade, but the brain areas causally involved in generating this symptom remain elusive. Here, we used data from 14 previously reported cases of lesion-induced oculogyric crises and employed lesion network mapping to identify their shared connections throughout the brain. This analysis yielded a common network that included basal ganglia, thalamic, and brainstem nuclei, as well as the cerebellum. Comparison of this network with gene expression profiles associated with the dopamine system revealed spatial overlap specifically with the gene coding for dopamine receptor type 2 (DRD2) as defined by a large-scale transcriptomic database of the human brain. Furthermore, spatial overlap with DRD2 and DRD3 gene expression was specific to brain lesions associated with oculogyric crises when contrasted to lesions that led to other movement disorders. Our findings identify a common neural network causally involved in the occurrence of oculogyric crises and provide a pathophysiological link between lesion locations causing this syndrome and its most common pharmacological cause, namely DRD2 blockade.

Global Perceptions and Utilization of Clinical Neurophysiology in Movement Disorders.

BACKGROUND: Clinical neurophysiology (CNP) involves the use of neurophysiological techniques to make an accurate clinical diagnosis, to quantify the severity, and to measure the treatment response. Despite several studies showing CNP to be a useful diagnostic tool in Movement Disorders (MD), its more widespread utilization in clinical practice has been limited. OBJECTIVES: To better understand the current availability, global perceptions, and challenges for implementation of diagnostic CNP in the clinical practice of MD. METHODS: The International Parkinson and Movement Disorders Society (IPMDS) formed a Task Force on CNP. The Task Force distributed an online survey via email to all the members of the IPMDS between August 5 and 30, 2021. Descriptive statistics were used for analysis of the survey results. Some results are presented by IPMDS geographical sections namely PanAmerican (PAS), European (ES), African (AFR), Asian and Oceanian (AOS). RESULTS: Four hundred and ninety-one IPMDS members (52% males), from 196 countries, responded. The majority of responders from the AFR (65%) and PAS (63%) sections had no formal training in diagnostic CNP (40% for AOS and 37% for ES). The most commonly used techniques are electroencephalography (EEG) (72%) followed by surface EMG (71%). The majority of responders think that CNP is somewhat valuable or very valuable in the assessment of MD. All the sections identified "lack of training" as one of the biggest challenges for diagnostic CNP studies in MD. CONCLUSIONS: CNP is perceived to be a useful diagnostic tool in MD. Several challenges were identified that prevent widespread utilization of CNP in MD.

Phytochemical Profiling and Biological Assessment of the Aerial Parts from Three Mediterranean Alkanna Species (A. orientalis, A. tinctoria, A. kotschyana) in the Boraginaceae Family.

This study focuses on the phytochemical analysis of the aerial parts of three Alkanna species: A. orientalis (L.) Boiss., A. tinctoria Tausch. and A. kotschyana A. DC. (Boraginaceae) growing wild in the Mediterranean basin, as mostly the roots of the genus have been widely researched. Their methanol extracts were subjected to qualitative LC-MS analyses, resulting in the annotation of 28 different secondary metabolites, with 27 originating from A. orientalis, 25 from A. tinctoria and 23 from A. kotschyana. The detected metabolites are categorized into three chemical types: organic acids (2), flavonoids and their glycosides (17), and caffeic acid derivatives (9). Furthermore, the chemical profiles of the three species are discussed chemotaxonomically. Caffeic acid and its derivatives, along with glucosides of quercetin and kaempferol, were identified in all three studied species. Additionally, their total phenolic and flavonoid contents were determined. The antioxidant capacity was evaluated through various chemical assays, as well as their in vitro enzyme inhibitory properties towards cholinesterases (AChE and BChE), α-amylase and α-glucosidase. The results showed that A. tinctoria exhibited the strongest antioxidant activity (211 mgTE/g extract in DPPH and 366 mgTE/g extract in ABTS), probably due to its high total phenolic (53.3 mgGAE/g extract) and flavonoid (20.8 mgRE/g extract) content, followed by A. kotschyana. These chemical and biological findings provide valuable insights for potential promising applications of the aerial parts of the species outside of the well-known uses of their roots.

The neural representation of actions in Tourette syndrome as a window to decipher tics and their suppression.

This scientific commentary refers to 'Elevated representational similarity of voluntary action and inhibition in Tourette syndrome', by Rae et al. (https://doi.org/10.1093/braincomms/fcad224).

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.

Study protocol: A cross-sectional survey of clinicians to identify barriers to clinical practice guideline implementation in the assessment and treatment of persistent tic disorders.

INTRODUCTION: Eight members of the International Parkinson's Disease and Movement Disorders Society Tic and Tourette Syndrome Study Group formed a subcommittee to discuss further barriers to practice guideline implementation. Based on expert opinion and literature review, the consensus was that practice variations continue to be quite broad and that many barriers in different clinical settings might negatively influence the adoption of the American Academy of Neurology and the European Society for the Study of Tourette Syndrome published guidelines. OBJECTIVES: 1) To identify how clinical practices diverge from the existing American Academy of Neurology and European Society for the Study of Tourette Syndrome guidelines, and 2) to identify categories of barriers leading to these clinical care gaps. METHODS AND ANALYSIS: This article presents the methodology of a planned cross-sectional survey amongst healthcare professionals routinely involved in the clinical care of patients with persistent tic disorders, aimed at 1) identifying how practices diverge from the published guidelines; and 2) identifying categories of barriers leading to these clinical care gaps. Purposeful sampling methods are used to identify and recruit critical persistent tic disorders stakeholders. The analysis will use descriptive statistics.

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.

Lesion-network mapping for tics: moving from replication to clinical translation.

This scientific commentary refers to 'Mapping a network for tics in Tourette syndrome using causal lesions and structural alterations', by Zouki et al. (https://doi.org/10.1093/braincomms/fcad105).

Phytochemical Study on Seeds of Paeonia clusii subsp. rhodia-Antioxidant and Anti-Tyrosinase Properties.

In this study, the black fertile (BSs) and the red unfertile seeds (RSs) of the Greek endemic Paeonia clusii subsp. rhodia (Stearn) Tzanoud were studied for the first time. Nine phenolic derivatives, trans-resveratol, trans-resveratrol-4'-O-ß-d-glucopyranoside, trans-ε-viniferin, trans-gnetin H, luteolin, luteolin 3'-O-ß-d-glucoside, luteolin 3',4'-di-O-ß-d-glucopyranoside, and benzoic acid, along with the monoterpene glycoside paeoniflorin, have been isolated and structurally elucidated. Furthermore, 33 metabolites have been identified from BSs through UHPLC-HRMS, including 6 monoterpene glycosides of the paeoniflorin type with the characteristic cage-like terpenic skeleton found only in plants of the genus Paeonia, 6 gallic acid derivatives, 10 oligostilbene compounds, and 11 flavonoid derivatives. From the RSs, through HS-SPME and GC-MS, 19 metabolites were identified, among which nopinone, myrtanal, and cis-myrtanol have been reported only in peonies' roots and flowers to date. The total phenolic content of both seed extracts (BS and RS) was extremely high (up to 289.97 mg GAE/g) and, moreover, they showed interesting antioxidative activity and anti-tyrosinase properties. The isolated compounds were also biologically evaluated. Especially in the case of trans-gnetin H, the expressed anti-tyrosinase activity was higher than that of kojic acid, which is a well-known whitening agent standard.

Microclimate and Genotype Impact on Nutritional and Antinutritional Quality of Locally Adapted Landraces of Common Bean (Phaseolus vulgaris L.).

This study aimed to assess the impact of genotype, location, and type of cultivation (organic) on the nutrient and anti-nutrient components of seven large-seeded bean (Phaseolus vulgaris L.) populations. All genotypes were cultivated during 2014 and 2015 in randomized complete block (RCB) experimental designs in three areas of the Prespa region (Pili, Patoulidio, Agios Germanos) in Greece. Particularly, total protein (18.79-23.93%), fiber (7.77-12%), starch (40.14-55.26%), and fat (1.84-2.58%) contents were analyzed and showed significant differences. In order to assess mineral content, firstly, the total ash percentage (4.31% to 5.20%) and secondly, trace elements and heavy metals were determined. The concentrations of identified inorganic metals showed large variations. The total phenolic content of the samples varied from 0.18 to 0.29 mg/g gallic acid equivalent (GAE). A major limitation of increasing the use of grain legumes as feed is the presence of diverse compounds in their grain, commonly referred to as antinutritional factors, and these are mainly trypsin inhibitors. Trypsin inhibitor levels were evaluated, with results varying from 21.8 to 138.5 TIU/g. Pili 2014 and 2015 were differently associated regarding the year of cultivation. Pili 2015 location was also very closely associated with the Patoulidio region, whereas Agios Germanos and Pili 2014 were the most different in terms of nutritional and antinutritional content.

Heliotropium procubens Mill: Taxonomic Significance and Characterization of Phenolic Compounds via UHPLC-HRMS- In Vitro Antioxidant and Enzyme Inhibitory Activities.

The aim of the present study was the phytochemical analysis of the aerial parts of Heliotropium procumbens Mill., a herb from Boraginaceae plant family not previously studied. The methanol (ME) and aqueous extracts (WE) of the aerial parts were assayed for their total phenolic and flavonoid content and antioxidant properties, using free radical scavenging (DPPH, ABTS), reducing power (FRAP, CUPRAC), phosphomolybdenum and metal chelating assays. The extracts displayed considerable free radical scavenging activity against DPPH and ABTS radicals, with potential values of 46.88 and 68.31 mg TE/g extract for ME, and 93.43 and 131.48 mg TE/g extract for WE, respectively. Key clinical enzymes involved in neurodegenerative diseases AChE and BChE, diabetes (α-amylase and α-glucosidase) and skin whitening (tyrosinase) were also assayed. The phytochemical profile of the studied species was determined through UHPLC-HRMS, whereby 26 secondary metabolites were identified, three of which (luteolin-7-glucoside, lithospermic and rosmarinic acids) were isolated and structurally determined by NMR spectral means. H. procubens was found to harbor bioactive metabolites and could, hence, serve as a source of biological activities which could be further explored and exploited for potential applications.

A Screening Tool to Quickly Identify Movement Disorders in Patients with Inborn Errors of Metabolism.

BACKGROUND: Movement disorders are frequent in patients with inborn errors of metabolism (IEMs) but poorly recognized, particularly by nonmovement disorder specialists. We propose an easy-to-use clinical screening tool to help recognize movement disorders. OBJECTIVE: The aim is to develop a user-friendly rapid screening tool for nonmovement disorder specialists to detect moderate and severe movement disorders in patients aged ≥4 years with IEMs. METHODS: Videos of 55 patients with different IEMs were scored by experienced movement disorder specialists (n = 12). Inter-rater agreements were determined on the presence and subtype of the movement disorder. Based on ranking and consensus, items were chosen to be incorporated into the screening tool. RESULTS: A movement disorder was rated as present in 80% of the patients, with a moderate inter-rater agreement (κ =0.420, P < 0.001) on the presence of a movement disorder. When considering only moderate and severe movement disorders, the inter-rater agreement increased to almost perfect (κ = 0.900, P < 0.001). Dystonia was most frequently scored (27.3%) as the dominant phenotype. Treatment was mainly suggested for patients with moderate or severe movement disorders. Walking, observations of the arms, and drawing a spiral were found to be the most informative tasks and were included in the screening tool. CONCLUSIONS: We designed a screening tool to recognize movement disorders in patients with IEMs. We propose that this screening tool can contribute to select patients who should be referred to a movement disorder specialist for further evaluation and, if necessary, treatment of the movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

Skin stretch modulates tactile distance perception without central correction mechanisms.

Tactile distance perception is influenced by stimulus orientation. On the hands or face, effects of orientation may originate from the mostly oval shape of receptive fields (RF) of which the long axis aligns with the proximodistal body axis. As tactile distance estimation relies on the number of RFs between stimuli, their alignment leads to a distortion of perception with distances being perceived as shorter in the proximodistal than the mediolateral body axis. It is however unknown, how physical manipulations such as skin stretch affect distance perception. Participants judged which of two distances aligned with the mediolateral or proximodistal axis on their dorsal dominant hand felt larger in two conditions: without physical manipulation and with proximodistal skin stretch. Distances were perceived shorter in proximodistal direction in both the nonstretch and the stretch condition, which was significantly pronounced in the stretch condition. Skin stretch led to perception of tactile distances as smaller, possibly related to the removal of afferent nerve endings and corresponding somatosensory RFs in the same external reference frame between the two touches. Though skin stretch is represented centrally, our results likely show that no correctional top-down mechanism corrects for skin stretch when estimating tactile distances. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Distinct movement disorders in contactin-associated-protein-like-2 antibody-associated autoimmune encephalitis.

Autoimmune encephalitis can be classified into antibody-defined subtypes, which can manifest with immunotherapy-responsive movement disorders sometimes mimicking non-inflammatory aetiologies. In the elderly, anti-LGI1 and contactin associated protein like 2 (CASPR2) antibody-associated diseases compose a relevant fraction of autoimmune encephalitis. Patients with LGI1 autoantibodies are known to present with limbic encephalitis and additionally faciobrachial dystonic seizures may occur. However, the clinical spectrum of CASPR2 autoantibody-associated disorders is more diverse including limbic encephalitis, Morvan's syndrome, peripheral nerve hyperexcitability syndrome, ataxia, pain and sleep disorders. Reports on unusual, sometimes isolated and immunotherapy-responsive movement disorders in CASPR2 autoantibody-associated syndromes have caused substantial concern regarding necessity of autoantibody testing in patients with movement disorders. Therefore, we aimed to systematically assess their prevalence and manifestation in patients with CASPR2 autoimmunity. This international, retrospective cohort study included patients with CASPR2 autoimmunity from participating expert centres in Europe. Patients with ataxia and/or movement disorders were analysed in detail using questionnaires and video recordings. We recruited a comparator group with anti-LGI1 encephalitis from the GENERATE network. Characteristics were compared according to serostatus. We identified 164 patients with CASPR2 autoantibodies. Of these, 149 (90.8%) had only CASPR2 and 15 (9.1%) both CASPR2 and LGI1 autoantibodies. Compared to 105 patients with LGI1 encephalitis, patients with CASPR2 autoantibodies more often had movement disorders and/or ataxia (35.6 versus 3.8%; P < 0.001). This was evident in all subgroups: ataxia 22.6 versus 0.0%, myoclonus 14.6 versus 0.0%, tremor 11.0 versus 1.9%, or combinations thereof 9.8 versus 0.0% (all P < 0.001). The small group of patients double-positive for LGI1/CASPR2 autoantibodies (15/164) significantly more frequently had myoclonus, tremor, 'mixed movement disorders', Morvan's syndrome and underlying tumours. We observed distinct movement disorders in CASPR2 autoimmunity (14.6%): episodic ataxia (6.7%), paroxysmal orthostatic segmental myoclonus of the legs (3.7%) and continuous segmental spinal myoclonus (4.3%). These occurred together with further associated symptoms or signs suggestive of CASPR2 autoimmunity. However, 2/164 patients (1.2%) had isolated segmental spinal myoclonus. Movement disorders and ataxia are highly prevalent in CASPR2 autoimmunity. Paroxysmal orthostatic segmental myoclonus of the legs is a novel albeit rare manifestation. Further distinct movement disorders include isolated and combined segmental spinal myoclonus and autoimmune episodic ataxia.