Activation of M4 muscarinic receptors in the striatum reduces tic-like behaviours in two distinct murine models of Tourette syndrome.

BACKGROUND AND PURPOSE: Current pharmacotherapies for Tourette syndrome (TS) are often unsatisfactory and poorly tolerated, underscoring the need for novel treatments. Insufficient striatal acetylcholine has been suggested to contribute to tic ontogeny. Thus, we tested whether activating M1 and/or M4 receptors-the two most abundant muscarinic receptors in the striatum-reduced tic-related behaviours in mouse models of TS. EXPERIMENTAL APPROACH: Studies were conducted using CIN-d and D1CT-7 mice, two TS models characterized by early-life depletion of striatal cholinergic interneurons and cortical neuropotentiation, respectively. First, we tested the effects of systemic and intrastriatal xanomeline, a selective M1/M4 receptor agonist, on tic-like and other TS-related responses. Then, we examined whether xanomeline effects were reduced by either M1 or M4 antagonists or mimicked by the M1/M3 agonist cevimeline or the M4 positive allosteric modulator (PAM) VU0467154. Finally, we measured striatal levels of M1 and M4 receptors and assessed the impact of VU0461754 on the striatal expression of the neural marker activity c-Fos. KEY RESULTS: Systemic and intrastriatal xanomeline reduced TS-related behaviours in CIN-d and D1CT-7 mice. Most effects were blocked by M4, but not M1, receptor antagonists. VU0467154, but not cevimeline, elicited xanomeline-like ameliorative effects in both models. M4, but not M1, receptors were down-regulated in the striatum of CIN-d mice. Additionally, VU0467154 reduced striatal c-Fos levels in these animals. CONCLUSION AND IMPLICATIONS: Activation of striatal M4, but not M1, receptors reduced tic-like manifestations in mouse models, pointing to xanomeline and M4 PAMs as novel putative therapeutic strategies for TS.

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

Tics emergencies and malignant tourette syndrome: Assessment and management.

Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the presence of tics, frequently accompanied by a variety of neuropsychiatric comorbidities. A subset of patients with TS present with severe and disabling symptoms, requiring prompt therapeutic intervention. Some of these manifestations may result in medical emergencies when severe motor or phonic tics lead to damage of anatomical structures closely related to the tic. Examples include myelopathy or radiculopathy following severe neck ("whiplash") jerks or a variety of self-inflicted injuries. In addition to self-aggression or, less commonly, allo-aggression, some patients exhibit highly inappropriate behavior, suicidal tendencies, and rage attacks which increase the burden of the disease and are important components of "malignant TS". This subset of TS is frequently associated with comorbid obsessive-compulsive disorder. Therapeutic measures include intensive behavioral therapy, optimization of oral pharmacotherapy, botulinum toxin injections, and deep brain stimulation.

Antidepressant-induced Paradoxical Anxiety, Akathisia, and Complex Vocal Tics in a Patient with Panic Disorder and Crohn's Disease: A Case Report.

BACKGROUND: Antidepressant-induced paradoxical anxiety is a fairly common phenomenon seen in patients who are initiated on antidepressants. However, akathisia is a very uncommon manifestation of antidepressants. Much more rarely, antidepressants are also associated with the emergence of motor and vocal tics. This case adds to the growing literature of rare adverse events induced by antidepressants and aims to stimulate future research into the mechanism and risk factors of this phenomenon. CASE PRESENTATION: In this case report, we describe a patient with panic disorder and co-morbid Crohn's disease who developed worsening anxiety, akathisia and vocal tics upon initiation of fluvoxamine. This is the first case report to describe the emergence of both akathisia and vocal tics in the same patient following antidepressant initiation. After discontinuation of fluvoxamine, the patient's symptoms resolved. CONCLUSION: Antidepressant-induced akathisia and tics are often distressing both to the patient and their loved ones, and can be very puzzling to the clinician. It is important for clinicians to recognise that, although rare, antidepressants can adverse effects. When these symptoms arise, it should prompt immediate discontinuation of the offending antidepressant.

Estilos de aprendizaje y Tecnologías de la Información y la Comunicación en la Educación Superior / Learning Styles and Information and Communication Technologies in Higher Education

Introducción: el desarrollo de preferencias con respecto a los estilos de aprendizaje de un estudiante universitario sufre variaciones porque la nueva era tecnológica provoca un cambio en la manera en que se aprende, dado por un punto convergente: las Tecnologías de la Información y la Comunicación y el uso del teléfono inteligente, entre otros dispositivos digitales. Objetivo: explicar aspectos conceptuales y metodológicos que establecen la necesidad de un adecuado binomio estilos de aprendizaje-TIC en el proceso de enseñanza aprendizaje (PEA) de la educación superior actual. Métodos: mediante el análisis documental se revisó la bibliografía en español e inglés entre 2012 y 2022, se emplearon las bases de datos: Redalyc, Dialnet, SciELO, y Google Scholar. Las palabras clave fueron: estilos de aprendizaje, tecnologías de la información y la comunicación y proceso de enseñanza aprendizaje. Los criterios de selección se aplicaron a 145 fuentes bibliográficas identificadas inicialmente y fueron seleccionados 25 artículos. Desarrollo: se confrontaron criterios y se emitieron juicios relacionados con la necesidad de preparación de los docentes universitarios para utilizar las Tecnologías de la Información y la Comunicación en el proceso de enseñanza aprendizaje, teniendo en cuenta los estilos de aprendizaje de los estudiantes. Conclusiones: los estudiantes universitarios han desarrollado los estilos de aprendizaje en función de las Tecnologías de la Información y la Comunicación, lo cual exige la preparación docente en función de aplicar estrategias metodológicas contextualizadas para el logro de un adecuado binomio estilos de aprendizaje-Tecnologías de la Información y la Comunicación, que garantice un mejor ejercicio de su profesión.

Introduction: the development of preferences with respect to the learning styles of a university student, it undergoes variations because the new technological era causes a change in the way in which one learns, given by a converging point: Information and Communication Technologies and the use of the smartphone, among other e- devices. Objective: explain conceptual and methodological aspects that establish the need for an adequate binomial of learning styles-ICT in the teaching-learning process (TLP) of current higher education. Methods: through documentary analysis, the bibliography was reviewed in Spanish and English from 2012 to 2022, the databases were used: Redalyc, Dialnet, SciELO, and Google Scholar. The keywords were: learning styles, information and communication technologies and teaching-learning process. The selection criteria were applied to 145 bibliographic sources initially identified and 25 articles were selected. Development: criteria were compared, and judgments were made related to the need to prepare university teachers to use Information and Communication Technologies in the teaching-learning process, considering the learning styles of the students. Conclusions: university students have developed learning styles based on Information and Communication Technologies, which requires teacher preparation based on applying contextualized methodological strategies to achieve an adequate binomial of learning styles-Information and Communication Technologies, which guarantees a better exercise of their profession.

Tecnologías e Integración de las Ciencias y la Educación Superior por un Desarrollo Sostenible / Technologies and Integration of Science and Higher Education for a Sustainable Development

El uso de las Tecnologías de la Información y las Comunicaciones ha tenido un impacto significativo en todas las áreas del conocimiento, de manera particular en los procesos sustantivos de la educación superior en las carreras tecnológicas de la salud. Es propósito de los autores informar sobre el uso de las Tecnologías de la Información y las Comunicaciones para la divulgación de actividades docentes, extensionistas e investigativas de la cátedra Integración de las Ciencias y la Educación Superior por un Desarrollo Sostenible. Se destaca la vinculación de dos proyectos de investigación científica con un fin único: la promoción de actividades educativas con herramientas digitales.

The use of Information and Communication Technologies has had a significant impact in all areas of knowledge, particularly in the substantive processes of higher education in health technology careers. It is the authors' purpose to report on the use of Information and Communication Technologies for the dissemination of teaching, extension and research activities of the chair Integration of Sciences and Higher Education for Sustainable Development. The linkage of two scientific research projects with a unique purpose: the promotion of educational activities with digital tools is highlighted.

Cytokine levels reflect tic symptoms more prominently during mild phases.

Tic disorder is a neuropsychiatric condition that affects 3% of all children and can have a significant impact on their quality of life. Cytokines, interferons, interleukins, lymphokines, and tumor necrosis factors are involved in the neuroinflammatory circuitry of tic disorders. This study aimed to identify the cytokines involved in the pathogenesis of tic disorders. We enrolled 44 patients with tic disorder and 38 healthy controls. Patients were free of psychotropic medications for at least 3 weeks. Whole blood samples were analyzed using a Luminex® human cytokine multiplex assay kit. Patients were divided into groups with "mild tics" and "above moderate tics" based on Yale Global Tic Severity Scale (YGTSS) scores for comparison. The final analysis included 35 patients (28 male and 7 female) and 31 controls (20 male and 11 female). In the mild tic group, interleukin (IL)-12 p70 negatively correlated with motor tic scores. Granulocyte-macrophage colony-stimulating factor, IL-4, IL-8, and tumor necrosis factor (TNF)-α were positively correlated to phonic tic scores. IL-12 p40 and TNF-α were positively correlated to total tic scores. IL-12 p70 and IL-17a negatively correlated to impairment scores and total YGTSS scores. Tic disorder patients and healthy controls exhibit different cytokine profiles. Only patients with mild symptoms exhibit significant correlations, suggesting that the correlations between cytokine levels and tic symptoms are more relevant during the mild or remission phases. Our results present the importance of IL-1ß and TNF-α, among others, but the identification of key cytokines are still necessary.

One-year outcomes of deep brain stimulation in refractory Tourette syndrome.

AIM: Deep brain stimulation (DBS) is one option for treating refractory Tourette syndrome (TS); however, it remains unclear which preoperative factors are predictive of DBS outcomes. This study investigated the efficacy of DBS targeting the anteromedial globus pallidus internus and evaluated predisposing factors affecting the outcomes of DBS in a single center in Korea. METHOD: Twenty patients who had undergone DBS for refractory TS were reviewed retrospectively. Tic symptoms were followed up at 3-month intervals for up to 1 year after surgery. The Yale Global Tic Severity Scale was used to evaluate preoperative/postoperative tic symptoms. Scores from the Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory-II, and Beck Anxiety Inventory were also evaluated. RESULTS: Patients with refractory TS achieved improvement in tic symptoms within 1 year after DBS. Initial responders who achieved a 35% reduction in Yale Global Tic Severity Scale total score within the first 3 months after DBS showed larger treatment effects during 1-year follow-up. Although no clinical or demographic factors were predictive of initial responses, patients with serious self-injurious behaviors tended to show delayed responses. CONCLUSION: This is the first study to our knowledge to report the DBS outcomes of 20 patients with TS in a single center in Asia. Our study supports the efficacy of DBS targeting anteromedial globus pallidus internus in refractory TS with no evident serious adverse events. Initial responses after DBS seem to be a predictor of long-term outcomes after surgery.

Prefrontal allopregnanolone mediates the adverse effects of acute stress in a mouse model of tic pathophysiology.

Ample evidence suggests that acute stress can worsen symptom severity in Tourette syndrome (TS); however, the neurobiological underpinnings of this phenomenon remain poorly understood. We previously showed that acute stress exacerbates tic-like and other TS-associated responses via the neurosteroid allopregnanolone (AP) in an animal model of repetitive behavioral pathology. To verify the relevance of this mechanism to tic pathophysiology, here we tested the effects of AP in a mouse model recapitulating the partial depletion of dorsolateral cholinergic interneurons (CINs) seen in post-mortem studies of TS. Mice underwent targeted depletion of striatal CINs during adolescence and were tested in young adulthood. Compared with controls, partially CIN-depleted male mice exhibited several TS-relevant abnormalities, including deficient prepulse inhibition (PPI) and increased grooming stereotypies after a 30-min session of spatial confinement - a mild acute stressor that increases AP levels in the prefrontal cortex (PFC). These effects were not seen in females. Systemic and intra-PFC AP administration dose-dependently worsened grooming stereotypies and PPI deficits in partially CIN-depleted males. Conversely, both AP synthesis inhibition and pharmacological antagonism reduced the effects of stress. These results further suggest that AP in the PFC mediates the adverse effects of stress on the severity of tics and other TS-related manifestations. Future studies will be necessary to confirm these mechanisms in patients and define the circuitry responsible for the effects of AP on tics.

Precision Mapping of Thalamic Deep Brain Stimulation Lead Positions Associated With the Microlesion Effect in Tourette Syndrome.

BACKGROUND: The microlesion effect refers to the improvement of clinical symptoms after deep brain stimulation (DBS) lead placement and is suggested to indicate optimal lead placement. Very few studies have reported its implications in neuropsychiatric disorders. OBJECTIVE: To evaluate the magnitude of the microlesion effect in Tourette syndrome and the relationship between the microlesion effect and the anatomic location of implanted DBS leads. METHODS: Six male patients were included. Their median age at surgery and follow-up period were 25 years (range, 18-47) and 12 months (range, 6-24), respectively. All patients were videotaped pre- and postoperatively, and tic frequencies were counted. We also analyzed the precision of lead placement and evaluated the normative connectome associated with the microlesion area. RESULTS: The microlesion effect was observed as an improvement in tic symptoms in all patients, and the long-term clinical outcomes were favorable. The median motor tic frequency was 20.2 tics/min (range, 9.7-60) at baseline and decreased to 3.2 tics/min (1.2-11.3) in patients on postoperative day 1 ( P = .043) and to 5.7 tics/min (range, 1.9-16.6) in patients on postoperative day 7 ( P = .028). Phonic tic tended to improve immediately after surgery although the changes were not significant. Image analyses revealed that the precise position of the electrode was directed toward the anteromedial centromedian nucleus. Normative connectome analysis demonstrated connections between improvement-related areas and wide areas of the prefrontal cortex. CONCLUSION: This study shows that the microlesion effect may seem as an immediate improvement after optimal DBS lead placement in patients with Tourette syndrome.

Complex motor tics and neurobehavioral syndrome in diencephalic-mesencephalic junction dysplasia: Association or causation?

Too little is known about DMJD in adults. Various phenotypic presentations in adults with DMJD and long-term follow-up is needed to further characterise this disease.

Inclusão Digital de idosos: as (TICs) e o uso do celular / Digital inclusion of seniors: the (ICTs) and the use of the smartphone

O envelhecimento humano é um fenômeno que vem crescendo em escala global e se constitui como um acontecimento que chama a atenção de alguns anos para cá. Outro fator de muita relevância na contemporaneidade são as Tecnologias da Informação e Comunicação (TICs) que nos possibilitam questionar quais são os significados atribuídos pelos idosos a essas tecnologias, levando em consideração o uso do smartphone. O presente estudo tem como objetivo conhecer de que forma os idosos utilizam e como se relacionam com este aparelho. Trata-se de um estudo quantitativo, em que a coleta de dados foi realizada por meio da aplicação de questionários a 100 pessoas com mais de sessenta anos, participantes de grupos de convivência em uma cidade do interior do Rio Grande do Sul. Os dados foram analisados pelo programa Statistical Package for the Social Sciences (SPSS) versão 25, possibilitando a análise por meio de uma estatística descritiva. A pesquisa possibilitou a compreensão de como os idosos se relacionam com esta tecnologia, as dificuldades de inserção em um mundo conectado e as limitações que estes apresentam ao manusear seu smartphone. Também foram listados os aplicativos mais utilizados pela categoria pesquisada, contemplando durante a discussão os benefícios de utilizarem as TICs e os sentimentos que acometem esses idosos.(AU)

Human aging is a phenomenon that has been growing on a global scale and constitutes an event that has drawn attention in recent years. Another very relevant factor in contemporaneity are the Information and Communication Technologies (ICTs) that allow us to question what are the meanings attributed by the elderly to these technologies, considering the use of smartphones. The present study aims to understand how the elderly use and relate to this device. This is a quantitative study, in which data collection was carried out by applying questionnaires to 100 people over sixty years old, participants of socialization groups in a city in the countryside of Rio Grande do Sul. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 25, enabling analysis by using descriptive statistics. The research made it possible to understand how the elderly relate to this technology, the difficulties of insertion in a connected world, and the limitations they present when handling their smartphone. The applications most used by this researched category were also listed, contemplating during the discussion the benefits of using ICTs and the feelings that affect these elderly people.(AU)

Treatment failure in persistent tic disorders: an expert clinicians' consensus-based definition.

A standardized definition of treatment failure in the management of tics is currently lacking. Such definition would prevent persistent use of unnecessary interventions and help clinicians to determine when to offer less established treatments (e.g., deep brain stimulation surgery). To achieve an expert consensus-based definition of failure of medical treatments for tics, we used a multi-step, multi-round, web-based Delphi approach involving international specialist clinicians with specific expertise in tic disorders. These experts were identified through professional networks or consortia related to chronic tic disorders. We created a survey and reviewed the questions with stakeholders prior to two rounds of Delphi surveys, followed by a final review and discussion among research team members. Both survey rounds were completed using a sample of 36 expert stakeholders from 14 countries, including neurologists, psychiatrists, and clinical psychologists. The Delphi process led to consensus on 10 statements which formed the final definition of treatment failure. The definition was structured and operationalized according to two separate sections, one for behavioral and one for pharmacological treatments. Core components of the definition and its operationalization included lack of efficacy, adherence, and tolerability, as well as a definition of failure of behavioral therapies as a whole, and of pharmacological therapies as a whole. The group concluded that the components of this specific definition reflect the range and complexity of characteristics to consider in establishing tic-related treatment failure. Future research should assess the feasibility of this operational definition and whether it will change clinical decision-making and improve management outcomes.

The tic in TikTok and (where) all systems go: Mass social media induced illness and Munchausen's by internet as explanatory models for social media associated abnormal illness behavior.

This paper explores the recent phenomenon of adolescents presenting en masse (both online and in clinical settings) with symptoms seemingly acquired from viewing illness-related content posted by social media influencers. The most frequently reproduced illnesses have included Dissociative Identity Disorder (DID) and Tourette Syndrome. It discusses evidence that the recent spate of new-onset, severe tics are a form of Mass Psychogenic Illness facilitated by social media networks (a phenomenon labeled Mass Social Media Induced Illness). It then suggests that many of those self-diagnosed with DID may be manifesting a similar, technologically-facilitated conversion phenomenon. It then explores another explanatory model: that these simulacra of DID and Tourette Syndrome may also arise via a mechanism more closely resembling social media facilitated Factitious Disorder. Similar presentations, of individuals falsifying cancer, have previously been labeled Munchausen's by Internet. It then proposes an overarching construct, Social Media Associated Abnormal Illness Behavior (SMAAIB), that is agnostic regarding phenomenology. Within this framework, it explores the ways in which de-commodifying attention, connection and care (measured once in appointments and admissions, now in 'likes' and 'shares') and obtaining a full picture of the patient's psychological, sociological and cultural grounding can offer deeper understanding and ultimately a path to wellness.

Polygenic and environmental determinants of tics in the Avon Longitudinal Study of Parents and Children.

Tourette syndrome (TS) is caused by multiple genetic and environmental factors. Yet, little is known about the interplay of these factors in the occurrence of tics. We investigated whether polygenic risk score (PRS) of TS and pregnancy-related factors together enhance the explained variance of tic occurrence in the Avon Longitudinal Study of Parents and Children (Ncases  = 612; Ncontrols  = 4,201; 50% male; mean age 13.8 years). We included a cumulative adverse pregnancy risk score, maternal anxiety and depression, and maternal smoking and alcohol use during pregnancy. We investigated possible joint effects of genetic and pregnancy-related risk factors using a multivariable approach, and explored mediation effects between the pregnancy-related risk factors in explaining tic presence. The PRS and the cumulative adverse pregnancy risk score, maternal anxiety, or maternal depression explained significantly more variance of tic presence compared to models including only the PRS. Furthermore, we found that the cumulative adverse pregnancy risk score mediated the association between several pregnancy-related factors (maternal anxiety, depression, and smoking) and tics. The combination of a PRS and pregnancy-related risk factors explained more variance of tics in a general population cohort compared to studying these factors in isolation.

Chromium (VI)-induced ALDH1A1/EGF axis promotes lung cancer progression.

Cr(VI) is broadly applied in industry. Cr(VI) exposure places a big burden on public health, thereby increasing the risk of lung squamous cell carcinoma (LUSC). The mechanisms underlying Cr(VI)-induced LUSC remain largely elusive. Here, we report that the cancer stem cell (CSC)/tumour-initiating cell (TIC)-like subgroup within Cr(VI)-transformed bronchial epithelial cells (CrT) promotes lung cancer tumourigenesis. Mechanistically, Cr(VI) exposure specifically increases the expression levels of aldehyde dehydrogenase 1A1 (ALDH1A1), a CSC marker, through KLF4-mediated transcription. ALDH1A1 maintains self-renewal of CrT/TICs and facilitates the expression and secretion of EGF from CrT/TICs, which subsequently promotes the activation of EGFR signalling in differentiated cancer cells and tumour growth of LUSC. In addition, the ALDH1A1 inhibitor A37 and gemcitabine synergistically suppress LUSC progression. Importantly, high ALDH1A1 expression levels are positively correlated with advanced clinical stages and predict poor survival in LUSC patients. These findings elucidate how ALDH1A1 modulates EGF secretion from TICs to facilitate LUSC tumourigenesis, highlighting new therapeutic strategies for malignant lung cancers.

Macrovascular Decompression with the Transposition Method Using Teflon Sling for Trigeminal Neuralgia Caused by the Vertebrobasilar Artery.

OBJECTIVE: Complete separation of the vertebrobasilar artery (VBA) from the trigeminal nerve by microvascular decompression is technically challenging. This paper evaluates the transposition method using Teflon sling for trigeminal neuralgia (TN) caused by the VBA. METHODS: Retrospective review of 32 patients including 2 patients with tic convulsif. Mobilization of the VBA in the anteromedial-caudal direction and repositioning of the VBA using Teflon sling and fibrin glue were performed. Pre- and postoperative pain were evaluated with the Barrow Neurological Institute (BNI) pain intensity score. Duration of surgery and postoperative neurologic complications were reviewed. RESULTS: Preoperative BNI score ranged from III to V. Postoperative BNI score I was observed in 30 patients, II in 1 patient, and V in 1 patient as recurrence. Abducens nerve palsy was observed in 9 patients but was transient in 8. Permanent hearing loss was observed in 6 patients. Transient mild lower cranial nerve palsy was recorded in 2 patients with tic convulsif. Average surgical time was 290 minutes. CONCLUSIONS: Our method for trigeminal neuralgia caused by VBA was very effective, but the complication rate of cranial nerve disorders was also high. A high rate of complications implied the technical difficulty of extensive vascular mobilization requiring long duration of surgery. Macrovascular decompression surgery is more descriptive of this surgery instead of microvascular decompression surgery.

Improved depressive symptoms in patients with refractory Gilles de la Tourette syndrome after deep brain stimulation of posteroventral globus pallidus interna.

OBJECTIVE: Deep brain stimulation (DBS) has been used on drug-resistant Gilles de la Tourette syndrome (GTS) for more than two decades until now, but the stimulating targets are still under exploration until now. In this study, the authors reported the efficacy of the bilateral posteroventral globus pallidus interna (GPi) DBS on tic severity and neuropsychiatry symptoms of seven individuals with GTS. METHOD: Seven patients with drug-resistant GTS were enrolled in this study. The severity of these patients was evaluated with Yale Global Tics Severity Scale (YGTSS), Yale Brown Obsessive Compulsive Scale (YBOCS), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and Global Assessment of Functioning Scale (GAF). Bilateral posteroventral GPi were selected as the permanent stimulating targets. Follow-up period was at least 5 years after surgery in the enrolled patients. RESULTS: After surgery, one patient reported no improvement during the follow-up period, and a device removal surgery was performed. The other six patients reported minor to significant improvement. The overall YGTSS, YBOCS, HAMA HAMD, and GAF scores of these patients were changed positively after surgery, but only the improvement of the motor tic and HAMD scores had a statistical difference. No surgical complication was reported. CONCLUSIONS: Bilateral posteroventral GPi DBS could relieve the motor tics and depressive symptoms of the enrolled patients significantly, but the vocal tics and other psychiatric symptoms presented a progression without statistical difference during the follow-up period. The results of this study suggested that bilateral posteroventral GPi are effective targets for the motor tics in GTS patients, especially with prominent depressive symptoms.

What makes tics tick? Insights into Tourette syndrome.

This issue of Biomedical Journal provides the reader with articles concerning the latest understanding of Tourette syndrome (TS), the relation to genetic predisposition, defects in the dopaminergic system, and related comorbidities which further complications like sleep disruption. Treatment approaches for TS, attention deficit hyperactivity disorder and developmental coordination disorder are discussed. The second section of this issue offers insights into inside out integrin activation and its link to T cell activation, demonstrates how polarity in immune cells allows adoption to specialized functions, and describes the endosomal signaling of internalized T cell receptors (TCRs). The link between mutations in TCR signaling and immunodeficiencies is elucidated, as well as the interactions of thymocyte-expressed molecule involved in selection in T cell development. Additionally, we learn about a potential biomarker for colorectal cancer, screening tools for determining frailty in older adults, surgical approaches in spinal metastases, the influence of autophagy on mating behavior, and the effect of nitrite administration on SNARE proteins associated with insulin secretion. Finally, parameters for surgery in breast cancer are discussed, as well as gender and age dependent pain perception in a lysosomal storage disease, and the use of laser meridian massage in opioid use disorder. Three letters complement this issue, one concerning neuroimaging in pediatric COVID-19 patients, and two discussing the role of cancer antigen-125 and renal impairment in ovarian cancer patients.