Personality and psychopathological characteristics in functional movement disorders.

INTRODUCTION: Aim of the present study was to assess personality and psychopathological characteristics in patients with functional movement disorders (FMDs) compared to patients with other neurological disorders (OND). METHODS: In this cross-sectional study, patients affected by clinically established FMDs and OND who attended the Neurologic Unit of the University-Hospital "Policlinico-San Marco" of Catania from the 1st of December 2021 to the 1st of June 2023 were enrolled. Personality characteristics were assessed with the Rorschach test coded according to Exner's comprehensive system and the Structured Clinical Interview for DSM-5 (SCID-II). RESULTS: Thirty-one patients with FMDs (27 women; age 40.2±15.5 years; education 11.7±3.2 years; disease duration 2.3±2.5 years) and 24 patients affected by OND (18 women; age 35.8±16.3 years; education 11.9±2.9 years; disease duration 3.4±2.8 years) were enrolled. At the Rorschach, FMDs presented a significantly higher frequency of Popular (P) and sum of all Human content codes (SumH>5) responses and avoidant coping than OND. CONCLUSION: FMDs presented "conformity behaviors", excessive interest in others than usual a maladaptive avoidant style of coping and a difficulty in verbalizing emotional distress. These psychopathological characteristics may favor the occurrence of FMDs.

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice / Tratamiento concomitante de safinamida y antidepresivos: Datos de seguridad sobre la práctica en la vida real

Background and purpose: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. Methods: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. Results: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years ± 8.43 and H&Y stage was 3 [2–4]. Mean dose of levodopa used was 703.75 mg ± 233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. Conclusions: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.(AU)

Objetivos: El objetivo de este estudio ha sido evaluar las posibles interacciones farmacológicas entre safinamida y antidepresivos; en particular la aparición del síndrome serotoninérgico mediante datos obtenidos en la vida real. Material y métodos: Realizamos un estudio observacional retrospectivo de pacientes con enfermedad de Parkinson (EP) de nuestra unidad de trastornos del movimiento, que estaban en tratamiento con algún fármaco antidepresivo y safinamida. Específicamente, se examinaron los síntomas sugestivos de síndrome serotoninérgico. Además, se recogieron tiempos de uso simultáneo, dosis de levodopa y otros fármacos antiparkinsonianos concomitantes. Resultados: Se revisaron las historias clínicas correspondientes al período de estudio de septiembre de 2018 a septiembre de 2019. Setenta y ocho pacientes con EP se encontraban en tratamiento con safinamida, de los cuales 25 (32,05%) se encontraban recibiendo además un fármaco antidepresivo, siendo sertralina y escitalopram los más frecuentes. La edad media fue de 80 años ± 8,43 y el estadio H&Y fue de 3 [2-4]. La dosis media de levodopa utilizada fue de 703,75 mg ± 233,15. La mediana de duración del tratamiento concomitante con safinamida y un fármaco antidepresivo fue de 6 meses (IQR: 20,5), y más de 18 meses en 5 casos. No se registró ningún caso de síndrome serotoninérgico, ni tampoco ninguno de sus síntomas de forma aislada. Conclusión: Nuestro estudio de práctica clínica real sugiere que el uso concomitante de safinamida con fármacos antidepresivos en pacientes con EP parece ser seguro y bien tolerado, incluso a largo plazo. Sin embargo, es necesaria precaución, individualizando los regímenes de tratamiento, y controlando la posible aparición de efectos adversos.(AU)

Role of Functional neurosurgery in Improving Patient Outcomes in Epilepsy, Movement Disorders, and Chronic Pain.

Functional neurosurgery encompasses surgical procedures geared towards treating movement disorders (such as Parkinson's disease and essential tremor), drug-resistant epilepsy, and various types of pain disorders. It is one of the most rapidly expanding fields within neurosurgery and utilizes both traditional open surgical methods such as open temporal lobectomy for epilepsy as well as neuromodulation-based treatments such as implanting brain or nerve stimulation devices. This review outlines the role functional neurosurgery plays in treatment of epilepsy, movement disorders, and pain, and how it is being implemented at the University of Missouri by the Department of Neurosurgery.

Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy.

BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

Emerging therapies for childhood-onset movement disorders.

PURPOSE OF REVIEW: We highlight novel and emerging therapies in the treatment of childhood-onset movement disorders. We structured this review by therapeutic entity (small molecule drugs, RNA-targeted therapeutics, gene replacement therapy, and neuromodulation), recognizing that there are two main approaches to treatment: symptomatic (based on phenomenology) and molecular mechanism-based therapy or 'precision medicine' (which is disease-modifying). RECENT FINDINGS: We highlight reports of new small molecule drugs for Tourette syndrome, Friedreich's ataxia and Rett syndrome. We also discuss developments in gene therapy for aromatic l-amino acid decarboxylase deficiency and hereditary spastic paraplegia, as well as current work exploring optimization of deep brain stimulation and lesioning with focused ultrasound. SUMMARY: Childhood-onset movement disorders have traditionally been treated symptomatically based on phenomenology, but focus has recently shifted toward targeted molecular mechanism-based therapeutics. The development of precision therapies is driven by increasing capabilities for genetic testing and a better delineation of the underlying disease mechanisms. We highlight novel and exciting approaches to the treatment of genetic childhood-onset movement disorders while also discussing general challenges in therapy development for rare diseases. We provide a framework for molecular mechanism-based treatment approaches, a summary of specific treatments for various movement disorders, and a clinical trial readiness framework.

Dancing Out of Step: A Case of Tuberculous Meningitis Presenting as Childhood Chorea.

Background: Acute to subacute pediatric movement disorders require prompt diagnosis to identify potentially treatable diseases. Case Report: We present a 6-year-old male with a three-week history of generalized chorea transitioning to predominantly right-sided hemichorea and then to left hemiplegia. Discussion: We review the mechanisms in tuberculous meningitis underlying his movement abnormalities.

Evaluate the in vitro effect of anthracycline and alkylating cytophosphane chemotherapeutics on dopaminergic neurons.

BACKGROUND: Iatrogenesis is an inevitable global threat to healthcare that drastically increases morbidity and mortality. Cancer is a fatal pathological condition that affects people of different ages, sexes, and races around the world. In addition to the detrimental cancer pathology, one of the most common contraindications and challenges observed in cancer patients is severe adverse drug effects and hypersensitivity reactions induced by chemotherapy. Chemotherapy-induced cognitive neurotoxicity is clinically referred to as Chemotherapy-induced cognitive impairment (CICI), chemobrain, or chemofog. In addition to CICI, chemotherapy also causes neuropsychiatric issues, mental disorders, hyperarousal states, and movement disorders. A synergistic chemotherapy regimen of Doxorubicin (Anthracycline-DOX) and Cyclophosphamide (Alkylating Cytophosphane-CPS) is indicated for the management of various cancers (breast cancer, lymphoma, and leukemia). Nevertheless, there are limited research studies on Doxorubicin and Cyclophosphamide's pharmacodynamic and toxicological effects on dopaminergic neuronal function. AIM: This study evaluated the dopaminergic neurotoxic effects of Doxorubicin and Cyclophosphamide. METHODS AND RESULTS: Doxorubicin and Cyclophosphamide were incubated with dopaminergic (N27) neurons. Neuronal viability was assessed using an MTT assay. The effect of Doxorubicin and Cyclophosphamide on various prooxidants, antioxidants, mitochondrial Complex-I & IV activities, and BAX expression were evaluated by Spectroscopic, Fluorometric, and RT-PCR methods, respectively. Prism-V software (La Jolla, CA, USA) was used for statistical analysis. Chemotherapeutics dose-dependently inhibited the proliferation of the dopaminergic neurons. The dopaminergic neurotoxic mechanism of Doxorubicin and Cyclophosphamide was attributed to a significant increase in prooxidants, a decrease in antioxidants, and augmented apoptosis without affecting mitochondrial function. CONCLUSION: This is one of the first reports that reveal Doxorubicin and Cyclophosphamide induce significant dopaminergic neurotoxicity. Thus, Chemotherapy-induced adverse drug reaction issues substantially persist during and after treatment and sometimes never be completely resolved clinically. Consequently, failure to adopt adequate patient care measures for cancer patients treated with certain chemotherapeutics might substantially raise the incidence of numerous movement disorders.

Syagrus coronata fixed oil prevents rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3-4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

Sleep quality and psychological health in patients with pelvic and acetabulum fractures: a cross-sectional study.

BACKGROUND AND OBJECTIVES: It is known that difficulty sleeping after a fracture can have negative effects on both mental and physical health and may prolong the recovery process. The objective of this study is to explore how sleep quality and psychological health are linked in patients with pelvic and acetabulum fractures. METHODS: A study was conducted on 265 patients between 2018 and 2022 who had suffered pelvic and acetabulum fractures. The study examined various factors, including age, gender, cause of injury, post-operative complications, and injury severity. The study employed ordinal logistic regression to examine the relationship between various pelvic fractures and seven subscales of the Majeed Pelvic Score (MPS), as well as the Sleep Disorder Questionnaire (SDQ) and Beck Depression Inventory (BDI). The study focused on the postoperative outcome one year after surgery, and each patient was assessed at the one-year mark after surgical intervention. Additionally, the study evaluated the functional outcome, sleep quality, and psychological disorders of the patients. RESULTS: From 2018 to 2022, a total of 216 patients suffered from pelvic and acetabulum fractures. Among them, 6.6% experienced borderline clinical depression, and 45.2% reported mild mood disturbances. Anxiety was found to be mild to moderate in 46% of Tile C and posterior acetabulum wall fracture patients. About 24.8% of patients reported insomnia, while 23.1% reported sleep movement disorders. However, no significant correlation was found between fracture types and sleep disorders. The mean Majeed pelvic score (MPS) was 89.68. CONCLUSIONS: Patients with pelvic and acetabular fractures typically experience functional improvement, but may also be at increased risk for insomnia and sleep movement disorders, particularly for certain types of fractures. Psychological well-being varies between fracture groups, with signs of borderline clinical depression observed in some cases. However, anxiety levels do not appear to be significantly correlated with pelvic and acetabular fractures.

The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency.

The objective of the study is to evaluate the evolving phenotype and genetic spectrum of patients with succinic semialdehyde dehydrogenase deficiency (SSADHD) in long-term follow-up. Longitudinal clinical and biochemical data of 22 pediatric and 9 adult individuals with SSADHD from the patient registry of the International Working Group on Neurotransmitter related Disorders (iNTD) were studied with in silico analyses, pathogenicity scores and molecular modeling of ALDH5A1 variants. Leading initial symptoms, with onset in infancy, were developmental delay and hypotonia. Year of birth and specific initial symptoms influenced the diagnostic delay. Clinical phenotype of 26 individuals (median 12 years, range 1.8-33.4 years) showed a diversifying course in follow-up: 77% behavioral problems, 76% coordination problems, 73% speech disorders, 58% epileptic seizures and 40% movement disorders. After ataxia, dystonia (19%), chorea (11%) and hypokinesia (15%) were the most frequent movement disorders. Involvement of the dentate nucleus in brain imaging was observed together with movement disorders or coordination problems. Short attention span (78.6%) and distractibility (71.4%) were the most frequently behavior traits mentioned by parents while impulsiveness, problems communicating wishes or needs and compulsive behavior were addressed as strongly interfering with family life. Treatment was mainly aimed to control epileptic seizures and psychiatric symptoms. Four new pathogenic variants were identified. In silico scoring system, protein activity and pathogenicity score revealed a high correlation. A genotype/phenotype correlation was not observed, even in siblings. This study presents the diversifying characteristics of disease phenotype during the disease course, highlighting movement disorders, widens the knowledge on the genotypic spectrum of SSADHD and emphasizes a reliable application of in silico approaches.

La actividad física en la enfermedad de Parkinson: identificación de los responsables de su prescripción, hábitos e impacto en la calidad de vida, y de la gravedad de la enfermedad / Physical activity in Parkinson’s disease: examining prescription sources, patterns, and the influence of quality of life and disease severity

Introducción: Escasas investigaciones han explorado la influencia de la calidad de vida (CV) y la gravedad de la enfermedad en la actividad física (AF) en pacientes con enfermedad de Parkinson (EP), así como las fuentes de prescripción de AF y consejos para esta población. Este estudio tiene como objetivo ampliar el conocimiento científico sobre estos temas. Pacientes y métodos: Se entrevistó personalmente a 211 pacientes con EP para recopilar datos sobre los niveles de AF con el International Physical Activity Questionnaire-Short Form y la CV con el Parkinson’s Disease Questionnaire-8. Un cuestionario ad hoc recopiló información sobre la gravedad de la enfermedad (etapas de Hoehn y Yahr), los comportamientos de AF y las recomendaciones de AF. Resultados: Se encontraron asociaciones débiles, pero significativas, entre los niveles de AF, la gravedad de la enfermedad (r = –0,218; p = 0,004) y la CV (r = –0,244; p = 0,001). La mayoría de los participantes (85%) recibió asesoramiento sobre AF, principalmente de neurólogos, ya sea en el momento del diagnóstico (52%) o poco después (28%). Antes del inicio de la EP, ~86% participaba en AF, lo que disminuyó al 66% después del diagnóstico. Aproximadamente el 78% informó sobre cambios en la AF, incluida una reducción en la frecuencia (18,4%) y la duración (32,8%), y la caminata era la actividad principal. Conclusiones: La gravedad de la enfermedad y la CV afectan significativamente a los niveles de AF en pacientes con EP. El diagnóstico se asocia con una disminución en la frecuencia y la duración de la AF, y la caminata es la actividad preferida. Los neurólogos aconsejan principalmente sobre AF a las personas con EP. (AU)

Introduction: Limited research has explored the influence of quality of life (QoL) and disease severity on physical activity (PA) in Parkinson’s disease (PD) patients, and the sources of PA prescription and advice for this population. This study aims to expand scientific knowledge on these topics. Patients and methods: Two-hundred eleven PD patients were personally interviewed to collect data on PA levels using the International Physical Activity Questionnaire-Short Form and QoL using the Parkinson’s Disease Questionnaire-8. An ad hoc questionnaire gathered information on disease severity (Hoehn and Yahr stages), PA behaviors, and PA recommendations. Results: Weak but significant associations were found between PA levels, disease severity (r: –0.218; p = 0.004), and QoL (r: –0.244; p = 0.001). Most participants (85%) received PA counselling, predominantly from neurologists, either at diagnosis (52%) or shortly after (28%). Before PD onset, ~86% engaged in PA, decreasing to 66% post-diagnosis. Approximately 78% reported changes in PA, including reduced frequency (18.4%) and duration (32.8%), with walking as the primary activity. Conclusions: Disease severity and QoL significantly affect PA levels in PD patients. Diagnosis is associated with decreased PA frequency and duration, and walking is the preferred activity. Neurologists primarily provide PA advice.(AU)

Burden of Neurologic Health Care and Incident Neurologic Diagnoses in the Year After COVID-19 or Influenza Hospitalization.

BACKGROUND AND OBJECTIVE: Following the outbreak of viral infections from the severe acute respiratory syndrome coronavirus 2 virus in 2019 (coronavirus disease 2019 [COVID-19]), reports emerged of long-term neurologic sequelae in survivors. To better understand the burden of neurologic health care and incident neurologic diagnoses in the year after COVID-19 vs influenza, we performed an analysis of patient-level data from a large collection of electronic health records (EMR). METHODS: We acquired deidentified data from TriNetX, a global health research network providing access to EMR data. We included individuals aged 18 years or older during index event, defined as hospital-based care for COVID-19 (from April 1, 2020, until November 15, 2021) or influenza (from 2016 to 2019). The study outcomes were subsequent health care encounters over the following year for 6 neurologic diagnoses including migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia. We also created a composite of the 6 diagnoses as an incident event, which we call "incident neurologic diagnoses." We performed a 1:1 complete case nearest-neighbor propensity score match on age, sex, race/ethnicity, marital status, US census region patient residence, preindex years of available data, and Elixhauser comorbidity score. We fit time-to-event models and reported hazard ratios for COVID-19 vs influenza infection. RESULTS: After propensity score matching, we had a balanced cohort of 77,272 individuals with COVID-19 and 77,272 individuals with influenza. The mean age was 51.0 ± 19.7 years, 57.7% were female, and 41.5% were White. Compared with patients with influenza, patients with COVID-19 had a lower risk of subsequent care for migraine (HR 0.645, 95% CI 0.604-0.687), epilepsy (HR 0.783, 95% CI 0.727-0.843), neuropathies (HR 0.567, 95% CI 0.532-0.604), movement disorders (HR 0.644, 95% CI 0.598-0.693), stroke (HR 0.904, 95% CI 0.845-0.967), or dementia (HR 0.931, 95% CI 0.870-0.996). Postinfection incident neurologic diagnoses were observed in 2.79% of the COVID-19 cohort vs 4.91% of the influenza cohort (HR 0.618, 95% CI 0.582-0.657). DISCUSSION: Compared with a matched cohort of adults with a hospitalization or emergency department visit for influenza infection, those with COVID-19 had significantly fewer health care encounters for 6 major neurologic diagnoses over a year of follow-up. Furthermore, we found that COVID-19 infection was associated with a lower risk of an incident neurologic diagnosis in the year after infection.

An Individualized Yoga Intervention for People with Functional Neurological Disorder: Case Series.

Functional neurological disorder (FND) is a heterogeneous condition of neurological symptoms that cannot be linked to a specific neurological cause. Yoga combines movement, breathing, and meditation and has established mind-body effects for people who are managing both psychological and neurological conditions. This case series describes key components of a yoga program for people with FND, evaluating feasibility, acceptability, and efficacy via self-report surveys, clinical assessments, and postintervention interview. Four individuals with FND participated in 45-minute, one-to-one virtual yoga sessions, two times a week for 8 weeks. We measured outcomes in four domains (healthcare utilization, FND symptoms, quality of life and self-efficacy, and function and mobility) at baseline, week 4, and week 8. Assessments included the Psychogenic Movement Disorders Rating Scale, timed up-and-go test, Patient Health Questionnaire-15, Brief Illness Perceptions Questionnaire, 36-Item Short Form Health Survey, and University of Washington Self-Efficacy Scale. Four participants completed at least 8 sessions, and two completed the full intervention (16 sessions). There were no adverse events. Two participants reported positive changes after yoga and improved on all clinical assessments (timed up-and-go test and Psychogenic Movement Disorders Rating Scale). Postintervention interview analysis revealed three themes: negative diagnosis experience, perceived health effects of yoga, and session format preferences. This was an exploratory case series describing a yoga intervention that was associated with some benefits for people with FND (decreased FND symptom severity and increased function, perceived health, quality of life, and self-efficacy). A larger case series is warranted to understand how to best select individuals who would benefit from the program.

Emergence of lingual dystonia and strabismus in early-onset SCN8A self-limiting familial infantile epilepsy.

Pathogenic variants in SCN8A are associated with a broad phenotypic spectrum, including Self-Limiting Familial Infantile Epilepsy (SeLFIE), characterized by infancy-onset age-related seizures with normal development and cognition. Movement disorders, particularly paroxysmal kinesigenic dyskinesia typically arising after puberty, may represent another core symptom. We present the case of a 1-year-old girl with a familial disposition to self-limiting focal seizures from the maternal side and early-onset orofacial movement disorders associated with SCN8A-SeLFIE. Brain MRI was normal. Genetic testing revealed a maternally inherited SCN8A variant [c.4447G > A; p.(Glu1483Lys)]. After the introduction of valproic acid, she promptly achieved seizure control as well as complete remission of strabismus and a significant decrease in episodes of tongue deviation. Family history, genetic findings, and epilepsy phenotype are consistent with SCN8A-SeLFIE. Movement disorders are an important part of the SCN8A phenotypic spectrum, and this case highlights the novel early-onset orofacial movement disorders associated with this condition. The episodes of tongue deviation and protrusion suggest focal oromandibular (lingual) dystonia. Additionally, while infantile strabismus or esophoria is a common finding in healthy individuals, our case raises the possibility of an ictal origin of the strabismus. This study underscores the importance of recognizing and addressing movement disorders in SCN8A-SeLFIE patients, particularly the rare early-onset orofacial manifestations. It adds to the growing body of knowledge regarding the diverse clinical presentations of SCN8A-associated disorders and suggests potential avenues for clinical management and further research.

Movement disorders associated with pediatric encephalitis.

New onset movement disorders are a common clinical problem in pediatric neurology and can be infectious, inflammatory, metabolic, or functional in origin. Encephalitis is one of the more important causes of new onset movement disorders, and movement disorders are a common feature (~25%) of all encephalitis. However, all encephalitides are not the same, and movement disorders are a key diagnostic feature that can help the clinician identify the etiology of the encephalitis, and therefore appropriate treatment is required. Movement disorders are a characteristic feature of autoimmune encephalitis such as anti-NMDAR encephalitis, herpes simplex virus encephalitis-induced autoimmune encephalitis, and basal ganglia encephalitis. Other rarer autoantibody-associated encephalitis syndromes with movement disorder associations include encephalitis associated with glycine receptor, DPPX, and neurexin-3 alpha autoantibodies. In addition, movement disorders can accompany acute disseminated encephalomyelitis with and without myelin oligodendrocyte glycoprotein antibodies. Extremely important infectious encephalitides that have characteristic movement disorder associations include Japanese encephalitis, dengue fever, West Nile virus, subacute sclerosing panencephalitis (SSPE), and SARS-CoV-2 (COVID-19). This chapter discusses how specific movement disorder phenomenology can aid clinician diagnostic suspicion, such as stereotypy, perseveration, and catatonia in anti-NMDAR encephalitis, dystonia-Parkinsonism in basal ganglia encephalitis, and myoclonus in SSPE. In addition, the chapter discusses how the age of the patients can influence the movement disorder phenomenology, such as in anti-NMDAR encephalitis where chorea is typical in young children, even though catatonia and akinesia is more common in adolescents and adults.

Neurological Practice in the Time of War: Perspectives and Experiences from Ukraine.

The full-scale Russian invasion of Ukraine has significantly impacted the country's healthcare system. Insufficient infrastructure, destruction of medical facilities, and barriers to prevention and treatment efforts hinder the provision of timely, high-quality care to our patients. We aim to describe the impact of the war on neurological care across Ukraine. In this article, leading national experts in stroke, epilepsy, multiple sclerosis, and movement disorders describe their personal experience and efforts in organizing and providing care since the war started in February 2022. A neurologist who cared for patients in Mariupol recounts the first weeks of the war when the city was under constant attacks. An international stroke expert describes the role of Task Force for Ukraine, a European Stroke Organization initiative to support the Ukrainian stroke community. We discuss a series of critical challenges facing Ukraine's neurologists, patients, and healthcare delivery system, including shortages of personnel and medical supplies, disrupted logistics, and lack of funding. In addition, we highlight various interventions and strategies aimed at counteracting these challenges, including international support, collaborations within Ukraine, and initiatives enhancing the resilience of the Ukrainian neurology community. As the war is ongoing, this article emphasizes the pressing need for continuous support and investment in the Ukrainian healthcare system to preserve guaranteed access to high-quality healthcare for the Ukrainian people during the war and in its aftermath. Insights from the essays can inform the development and implementation of effective strategies and interventions tailored to such extraordinary circumstances.

Real-time field-programmable gate array-based closed-loop deep brain stimulation platform targeting cerebellar circuitry rescues motor deficits in a mouse model of cerebellar ataxia.

AIMS: The open-loop nature of conventional deep brain stimulation (DBS) produces continuous and excessive stimulation to patients which contributes largely to increased prevalence of adverse side effects. Cerebellar ataxia is characterized by abnormal Purkinje cells (PCs) dendritic arborization, loss of PCs and motor coordination, and muscle weakness with no effective treatment. We aim to develop a real-time field-programmable gate array (FPGA) prototype targeting the deep cerebellar nuclei (DCN) to close the loop for ataxia using conditional double knockout mice with deletion of PC-specific LIM homeobox (Lhx)1 and Lhx5, resulting in abnormal dendritic arborization and motor deficits. METHODS: We implanted multielectrode array in the DCN and muscles of ataxia mice. The beneficial effect of open-loop DCN-DBS or closed-loop DCN-DBS was compared by motor behavioral assessments, electromyography (EMG), and neural activities (neurospike and electroencephalogram) in freely moving mice. FPGA board, which performed complex real-time computation, was used for closed-loop DCN-DBS system. RESULTS: Closed-loop DCN-DBS was triggered only when symptomatic muscle EMG was detected in a real-time manner, which restored motor activities, electroencephalogram activities and neurospike properties completely in ataxia mice. Closed-loop DCN-DBS was more effective than an open-loop paradigm as it reduced the frequency of DBS. CONCLUSION: Our real-time FPGA-based DCN-DBS system could be a potential clinical strategy for alleviating cerebellar ataxia and other movement disorders.

An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders.

Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that "extrapyramidal symptoms" is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception that all DIMDs can be treated in the same way, potentially leading to the misuse and overprescribing of anticholinergics. DIMDs are neurobiologically and clinically distinct, with different treatment paradigms and varying levels of evidence for anticholinergic use. Whereas evidence indicates anticholinergics can be effective for DIP and dystonia, they are not recommended for TD, akathisia, or NMS; nor are they supported for preventing DIMDs except in individuals at high risk for acute dystonia. Anticholinergics may induce serious peripheral adverse effects (e.g., urinary retention) and central effects (e.g., impaired cognition), all of which can be highly concerning especially in older adults. Appropriate use of anticholinergics therefore requires careful consideration of the evidence for efficacy (e.g., supportive for DIP but not TD) and the risks for serious adverse events. If used, anticholinergic medications should be prescribed at the lowest effective dose and for limited periods of time. When discontinued, they should be tapered gradually.

Genetic testing for non-parkinsonian movement disorders: Navigating the diagnostic maze.

Genetic testing has become a valuable diagnostic tool for movement disorders due to substantial advancements in understanding their genetic basis. However, the heterogeneity of movement disorders poses a significant challenge, with many genes implicated in different subtypes. This paper aims to provide a neurologist's perspective on approaching patients with hereditary hyperkinetic disorders with a focus on select forms of dystonia, paroxysmal dyskinesia, chorea, and ataxia. Age at onset, initial symptoms, and their severity, as well as the presence of any concurrent neurological and non-neurological features, contribute to the individual clinical profiles of hereditary non-parkinsonian movement disorders, aiding in the selection of appropriate genetic testing strategies. There are also more specific diagnostic clues that may facilitate the decision-making process and may be highly specific for certain conditions, such as diurnal fluctuations and l-dopa response in dopa-responsive dystonia, and triggering factors, duration and frequency of attacks in paroxysmal dyskinesia. While the genetic and mutational spectrum across non-parkinsonian movement disorders is broad, certain groups of diseases tend to be associated with specific types of pathogenic variants, such as repeat expansions in many of the ataxias. Some of these pathogenic variants cannot be detected by standard methods, such as panel or exome sequencing, but require the investigation of intronic regions for repeat expansions, such as Friedreich's or FGF14-linked ataxia. With our advancing knowledge of the genetic underpinnings of movement disorders, the incorporation of precise and personalized diagnostic strategies can enhance patient care, prognosis, and the application and development of targeted therapeutic interventions.

Paraneoplastic movement disorders.

Paraneoplastic movement disorders are diverse autoimmune neurological illnesses occurring in the context of systemic cancer, either in isolation or as part of a multifocal neurological disease. Movement phenomena may be ataxic, hypokinetic (parkinsonian), or hyperkinetic (myoclonus, chorea, or other dyskinetic disorders). Some disorders mimic neurodegenerative or hereditary illnesses. The subacute onset and coexisting nonclassic features of paraneoplastic disorders aid distinction. Paraneoplastic autoantibodies provide further information regarding differentiating cancer association, disease course, and treatment responses. A woman with cerebellar ataxia could have metabotropic glutamate receptor 1 autoimmunity, in the setting of Hodgkin lymphoma, a mild neurological phenotype and response to immunotherapy. A different woman, also with cerebellar ataxia, could have Purkinje cytoplasmic antibody type 1 (anti-Yo), accompanying ovarian adenocarcinoma, a rapidly progressive phenotype and persistent disabling deficits despite immune therapy. The list of antibody biomarkers is growing year-on-year, each with its own ideal specimen type for detection (serum or CSF), accompanying neurological manifestations, cancer association, treatment response, and prognosis. Therefore, a profile-based approach to screening both serum and CSF is recommended. Immune therapy trials are generally undertaken, and include one or more of corticosteroids, IVIg, plasma exchange, rituximab, or cyclophosphamide. Symptomatic therapies can also be employed for hyperkinetic disorders.