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.

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.

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.

Symptom Network Analysis in a Large Sample of Children and Adults with a Chronic Tic Disorder.

BACKGROUND: Chronic tic disorders (CTD) are multifaceted disorders characterized by multiple motor and/or vocal tics. They are often associated with complex tics including echophenomena, paliphenomena, and coprophenomena as well as psychiatric comorbidities such as attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). OBJECTIVES: Our goal was to uncover the inter-relational structure of CTD and comorbid symptoms in children and adults and to understand changes in symptom structure across development. METHODS: We used network and graph analyses to uncover the structure of association of symptoms in childhood/adolescence (n = 529) and adulthood (n = 503) and how this structure might change from childhood to adulthood, pinpointing core symptoms as a main target for interventions. RESULTS: The analysis yielded core symptom networks in young and adult patients with CTD including complex tics and tic-related phenomena as well as touching people and objects. Core symptoms in childhood also included ADHD symptoms, whereas core symptoms in adults included symptoms of OCD instead. Interestingly, self-injurious behavior did not play a core role in the young CTD network, but became one of the central symptoms in adults with CDT. In addition, we found strong connections between complex motor and vocal tics as well as echolalia and echopraxia. CONCLUSIONS: Next to other complex tics, echophenomena, paliphenomena, and coprophenomena can be regarded core symptoms of CTD. ADHD symptoms are closely related to CTD in childhood, whereas symptoms of OCD and self-injurious behavior are closely associated with CTD in adults. Our results suggest that a differentiation between motor and vocal tics is somewhat arbitrary.

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.

Neurologic Care for Transgender and Gender-Diverse People: A Review of Current Evidence and Clinical Implications.

Purpose of Review: To summarize the literature on neurologic care for transgender and gender-diverse (TGD) people and provide implications for clinical practice. Recent Findings: There are limited data on the frequency and management of neurologic conditions among TGD people. TGD people have a higher prevalence of various neurologic conditions compared with cisgender or general population cohorts, including migraine, subjective cognitive decline, sleep disturbances, functional disorders, and cerebrovascular disease. Gender-affirming hormone therapy interacts with commonly prescribed neurologic medications and increases stroke risk among transfeminine people. Sex hormones and sex chromosomes may play a role in neurodegeneration and disability progression in neuroimmunologic diseases. Clitoral reduction surgeries on intersex children can cause neurologic disability and sexual dysfunction in adulthood. Socioeconomic disparities among TGD people contribute to health care barriers. Summary: Neurologists should consider the unique experiences and health care needs of TGD people in their clinical practice and research protocols.

Engaging dystonia networks with subthalamic stimulation.

Deep brain stimulation is a viable and efficacious treatment option for dystonia. While the internal pallidum serves as the primary target, more recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its complex surroundings have not been studied in depth. Indeed, multiple historical targets that have been used for surgical treatment of dystonia are directly adjacent to the STN. Further, multiple types of dystonia exist, and outcomes are variable, suggesting that not all types would profit maximally from the exact same target. Therefore, a thorough investigation of the neural substrates underlying effects on dystonia symptoms is warranted. Here, we analyze a multi-center cohort of isolated dystonia patients with subthalamic implantations (N = 58) and relate their stimulation sites to improvement of appendicular and cervical symptoms as well as blepharospasm. Stimulation of the ventral oral posterior nucleus of thalamus and surrounding regions was associated with improvement in cervical dystonia, while stimulation of the dorsolateral STN was associated with improvement in limb dystonia and blepharospasm. This dissociation was also evident for structural connectivity, where the cerebellothalamic, corticospinal and pallidosubthalamic tracts were associated with improvement of cervical dystonia, while hyperdirect and subthalamopallidal pathways were associated with alleviation of limb dystonia and blepharospasm. Importantly, a single well-placed electrode may reach the three optimal target sites. On the level of functional networks, improvement of limb dystonia was correlated with connectivity to the corresponding somatotopic regions in primary motor cortex, while alleviation of cervical dystonia was correlated with connectivity to the recently described 'action-mode' network that involves supplementary motor and premotor cortex. Our findings suggest that different types of dystonia symptoms are modulated via distinct networks. Namely, appendicular dystonia and blepharospasm are improved with modulation of the basal ganglia, and, in particular, the subthalamic circuitry, including projections from the primary motor cortex. In contrast, cervical dystonia was more responsive when engaging the cerebello-thalamo-cortical circuit, including direct stimulation of ventral thalamic nuclei. These findings may inform DBS targeting and image-based programming strategies for patient-specific treatment of dystonia.