Neurological Movement Disorder Research Articles

ITex Gloves: Design and In-Home Evaluation of an E-Textile Glove System for Tele-Assessment of Parkinson’s Disease

Parkinson's disease (PD) is a neurological progressive movement disorder, affecting more than 10 million people globally. PD demands a longitudinal assessment of symptoms to monitor the disease progression and manage the treatments. Existing assessment methods require patients with PD (PwPD) to visit a clinic every 3-6 months to perform movement assessments conducted by trained clinicians. However, periodic visits pose barriers as PwPDs have limited mobility, and healthcare cost increases. Hence, there is a strong demand for using telemedicine technologies for assessing PwPDs in remote settings. In this work, we present an in-home telemedicine kit, named iTex (intelligent Textile), which is a patient-centered design to carry out accessible tele-assessments of movement symptoms in people with PD. iTex is composed of a pair of smart textile gloves connected to a customized embedded tablet. iTex gloves are integrated with flex sensors on the fingers and inertial measurement unit (IMU) and have an onboard microcontroller unit with IoT (Internet of Things) capabilities including data storage and wireless communication. The gloves acquire the sensor data wirelessly to monitor various hand movements such as finger tapping, hand opening and closing, and other movement tasks. The gloves are connected to a customized tablet computer acting as an IoT device, configured to host a wireless access point, and host an MQTT broker and a time-series database server. The tablet also employs a patient-centered interface to guide PwPDs through the movement exam protocol. The system was deployed in four PwPDs who used iTex at home independently for a week. They performed the test independently before and after medication intake. Later, we performed data analysis of the in-home study and created a feature set. The study findings reported that the iTex gloves were capable to collect movement-related data and distinguish between pre-medication and post-medication cases in a majority of the participants. The IoT infrastructure demonstrated robust performance in home settings and offered minimum barriers for the assessment exams and the data communication with a remote server. In the post-study survey, all four participants expressed that the system was easy to use and poses a minimum barrier to performing the test independently. The present findings indicate that the iTex glove system has the potential for periodic and objective assessment of PD motor symptoms in remote settings.

Development of a New Care Pathway for Depression and Anxiety in Adult-Onset Isolated Dystonia.

Recently, we identified barriers and facilitators to the screening and treatment of depressive and anxiety symptoms in adult-onset isolated dystonia (AOID). These symptoms are common, functionally impairing, and often underdetected and undertreated. To develop a care pathway for mood symptoms in AOID. We used a multistep modified Delphi approach to seek consensus among healthcare professionals with experience of AOID on the screening, diagnosis, and treatment of mood symptoms. A combination of face-to-face meetings and online surveys was performed from 2019 to 2020. We created the survey and then reviewed with stakeholders before 2 rounds of Delphi surveys, all of which was finally reviewed in a consensus meeting. A purposive sample of 41 expert stakeholders from 4 Canadian provinces, including neurologists, nurses, psychiatrists, psychologists, and family physicians, was identified by the research team. The Delphi process led to consensus on 12 statements that operationalized a pathway of care to screen for and manage depression and anxiety in people with AOID. Key actions of the pathway included yearly screening with self-rated instruments, multidisciplinary involvement in management involving local networks of providers coordinated by movement disorders neurologists, and access to educational resources. The Delphi panel indicated the 2 core steps as the documentation of the most recent screening outcome and the documentation of a management plan for patients who were positive at the last screening. This new care pathway represents a potentially useful intervention that can be used to build an integrated model of care for AOID.

Determinants of gait dystonia severity in cerebral palsy.

To determine the movement features governing expert assessment of gait dystonia severity in individuals with cerebral palsy (CP). In this prospective cohort study, three movement disorder neurologists graded lower extremity dystonia severity in gait videos of individuals with CP using a 10-point Likert-like scale. Using conventional content analysis, we determined the features experts cited when grading dystonia severity. Then, using open-source pose estimation techniques, we determined gait variable analogs of these expert-cited features correlating with their assessments of dystonia severity. Experts assessed videos from 116 participants (46 with dystonia aged 15 years [SD 3] and 70 without dystonia aged 15 years [SD 2], both groups ranging 10-20 years old and 50% male). Variable limb adduction was most commonly cited by experts when identifying dystonia, comprising 60% of expert statements. Effect on gait (regularity, stability, trajectory, speed) and dystonia amplitude were common features experts used to determine dystonia severity, comprising 19% and 13% of statements respectively. Gait variables assessing adduction variability and amplitude (inter-ankle distance variance and foot adduction amplitude) were significantly correlated with expert assessment of dystonia severity (multiple linear regression, p < 0.001). Adduction variability and amplitude are quantifiable gait features that correlate with expert-determined gait dystonia severity in individuals with CP. Consideration of these features could help optimize and standardize the clinical assessment of gait dystonia severity in individuals with CP.

Clinical features of dystonia and the science of classification.

This chapter describes advances in understanding the clinical features of dystonia since initial clinical recognition and its organization into a coherent and systematic clinical set. The clinical features of dystonia were at first considered an odd neurological movement disorder. Etymology of the word misleadingly underlined muscle tone. The main clinical features of dystonia were recognized gradually. They encompass dystonic movements, dystonic postures, alleviating maneuvers, overflow and mirroring. These features are observed in patients who present a variety of syndromes where dystonia occurs in isolation or combined with other movement disorders, or with other neurologic or systemic features. A large number of syndromic combinations is observed in the clinic and some of the syndomes are highlighted here. Practitioners are required to exert dedicated skills to recognize dystonia and correctly diagnose and classify their patients.

Psychometric properties and construct validity of the Parkinson's Disease-Cognitive Rating Scale (PD-CRS) in Colombia.

Cognitive impairment is frequent among people living with Parkinson's disease: up to 40% of patients exhibit symptoms of mild cognitive impairment and 25% meet the criteria for dementia. Parkinson's Disease Cognitive Rating Scale (PD-CRS) is one of the recommended scales by the Movement Disorders Society Task Force for level 1 screening of dementia. However, its psychometric properties have not been studied in the Colombian population. A cross-sectional study was conducted on 100 patients with Parkinson's disease diagnosed by a movement disorders neurologist. Patients were evaluated with PD-CRS and MoCA. Principal component analysis was conducted, and then confirmatory factor analysis was implemented through the maximum-likelihood method. Internal consistency was evaluated using Cronbach α. Convergent and divergent validity were also calculated and concurrent validity with the MoCA was assessed. 62% were males. Their median age was 68 years (IQR 57-74) and the median disease duration was 4 years (IQR 2-9). 77% were classified in early stages (Hoehn and Yahr stage ≤ 2), while the MDS-UPDRS part III score was 25 (IQR 15.5-38). In the principal component factor analysis, the pattern matrix unveiled a mnesic and a non-mnesic domain. Confirmatory factor analysis showed similar explanatory capacity (λ ≥ 0.50) for items other than naming (λ = 0.34). Cronbach's α for the full 9-items instrument was 0.74. MoCA and PD-CRS total scores were correlated (ρ = 0.71, p = 0.000). Assuming a cut-off score of 62 points, there is an agreement of 89% with the definition of dementia by MoCA for Colombia (κ = 0.59; p = 0.000). PD-CRS has acceptable psychometric properties for the Colombian population and has significant correlation and agreement with a validated scale (MoCA).

Towards a telehealth infrastructure supported by machine learning on edge/fog for Parkinson's movement screening

Approximately 10 million people worldwide live with Parkinson's disease (PD), a progressive and incurable neurological movement disorder. Symptomatic treatment is available for PD but requires patients to make periodic clinic visits (2–3 times per year) for symptom assessment. Advanced telehealth technologies can enhance clinical care for PD but warrant an Internet-of-Things-based (IoT) infrastructure that can enable symptom monitoring in out-of-clinic settings, such as homes. In this paper, we present an edge and Fog device-based IoT framework and a machine learning-based telehealth infrastructure that can detect and classify hand movement tasks based on a clinical test (UPDRS) for remote symptom assessment. We used a pair of smart gloves integrated with finger flex sensors, an inertial measurement unit (IMU), and a wireless embedded system (i.e., an edge device) to record the hand movements. The edge device (ESP32) detected the activity on the edge node and transmitted the data to the Fog node for classification. The Fog node (Raspberry pi) hosted the Machine Learning (ML) based activity classification models to classify UPDRS-based hand movement tasks. In this paper, we present the development of edge-fog-supported ML infrastructure. To develop ML models, we utilized the data of 9 participants (five healthy and four people with PD) who performed hand movements tasks while wearing the smart gloves. We developed and tested different classification models such as K-nearest neighbors (KNN), Support Vector Machine (SVM), and Decision Tree (DT) to identify which one fits best for such an edge-fog infrastructure for remote symptom assessment. Results showed that the SVM model outperformed others by giving 94% training, 94% testing, and 93% validation accuracy with a mean inference time of 560 μs on the Fog node. Our preliminary results are promising to further our research in deploying the edge-fog-driven ML-based telehealth infrastructure in real-world settings. • Development of Edge-Fog-supported telehealth IoT infrastructure. • Development and assessment of Machine Learning classifiers for hand movement activity classification. • Deployment and evaluation of the ML classification models on the Fog infrastructure. • Demonstration of how an edge-fog computing architecture can be useful for telehealth applications, including movement assessment, symptom tracking, and symptom management.

Atypical nuclear envelope condensates linked to neurological disorders reveal nucleoporin-directed chaperone activities.

DYT1 dystonia is a debilitating neurological movement disorder arising from mutation in the AAA+ ATPase TorsinA. The hallmark of Torsin dysfunction is nuclear envelope blebbing resulting from defects in nuclear pore complex biogenesis. Whether blebs actively contribute to disease manifestation is unknown. We report that FG-nucleoporins in the bleb lumen form aberrant condensates and contribute to DYT1 dystonia by provoking two proteotoxic insults. Short-lived ubiquitylated proteins that are normally rapidly degraded partition into the bleb lumen and become stabilized. In addition, blebs selectively sequester a specific HSP40-HSP70 chaperone network that is modulated by the bleb component MLF2. MLF2 suppresses the ectopic accumulation of FG-nucleoporins and modulates the selective properties and size of condensates in vitro. Our study identifies dual mechanisms of proteotoxicity in the context of condensate formation and establishes FG-nucleoporin-directed activities for a nuclear chaperone network.

Cost and Return on Investment of a Team-Based Palliative Care Program for Parkinson Disease.

Implementation of palliative care (PC) in neurology settings may improve symptom control and quality of life and reduce acute care admissions. The benefits of team-based PC for patients with Parkinson disease have been established through rigorous evidence standards including randomized controlled trials. However, evidence on implementation costs and return on investment (ROI) is unknown and may guide other providers and systems considering this model of care. We applied time-driven activity-based costing with reimbursable visits calculated using Medicare reimbursement rates in Colorado and current procedural technology codes to 2 outpatient clinics at the University of Colorado Hospital: neurology PC and movement disorders. Per-patient ROI was calculated as the ratio of the incremental difference in financial revenues divided by the incremental difference in investment to expand PC services. The cost per new patient was $154 and $98 for neuropalliative and movement disorders clinics, respectively. Established patient visit costs were $82 and $41 for the neuropalliative care and movement disorders clinics, respectively. The neurology PC clinic had per-patient revenue for new and established visits of $297 and $147, respectively, compared with $203 and $141 for new and established visits, respectively, at the comparator clinic. Based on our assumptions, for every $1 invested in expanding PC services, a projected $1.68 will be recouped by the hospital system for new patient visits, and $0.13 will be recouped for established patient visits. These amounts are context dependent, and a calculator was created to allow other systems to estimate costs and ROI. Our results suggest that in an academic medical setting, both neurology PC and movement disorders clinics provided increased revenue to the health system. Opportunities to improve ROI include efficient allocation of personnel to new and established visits, expanding telemedicine, and other cost offsets for complex patients not estimated in this analysis. ROI may also be greater in health systems that benefit from cost savings such as accountable care organizations. Our approach may be applied to other novel care models. Future research efforts will focus on estimating the continued sustainability of this innovative outpatient care model.

Epicranial Direct Current Stimulation Suppresses Harmaline Tremor in Rats

IntroductionEssential tremor (ET) is the most common neurologic movement disorder worldwide. It is characterized by a postural tremor, mostly in the upper extremities, causing difficulties in daily activities that may lead to social exclusion. Some patients with ET do not respond well to or do not tolerate medication. Thus, deep brain stimulation can be offered. In a recent study, we proposed a novel neuromodulation technique called epicranial current stimulation (ECS) that works in a minimally invasive way by placing the electrodes subcutaneously under the skin and directly over the skull. In this study, we investigated the feasibility of using epicranial direct current stimulation (EDCS) to suppress tremor in a rat harmaline ET model. Materials and MethodsIn experiment 1, seven Sprague Dawley rats were implanted with ECS electrodes placed over the motor cortex (MC) and the cerebellum to investigate whether stimulating between them could suppress tremor. In experiments 2 and 3, eight rats were implanted with ECS electrodes placed over the MC, cerebellum, and the rostral skull to separate the effects on tremor caused by stimulating each target. During each experiment, the rats were injected with harmaline, which induced tremor that was quantified using an accelerometer. EDCS was then applied through the different electrode configurations to evaluate their tremor suppression effectiveness. ResultsResults from experiment 1 showed that MCcathode-Cerebellaranode suppressed tremor compared with stimulation-OFF but MCanode-Cerebellarcathode did not. Furthermore, experiments 2 and 3 showed that it was the cerebellar anodal electrode that was driving tremor suppression. ConclusionCerebellar EDCS suppressed harmaline tremor in rats in a polarity-dependent manner. EDCS could be a promising neuromodulation method for patients with ET.

Musicians Focal Dystonia: The Practitioner's Perspective on Psychological, Psychosocial, and Behavioural Risk Factors and Non-motor Symptoms.

Musician's focal dystonia (MFD) is a painless, task-specific neurological movement disorder that impairs fine motor control when playing an instrument. The pathophysiology is not fully understood, and while the available treatment strategies can help with improving motor control, they are rarely able to fully and reliably rehabilitate playing skills. Recent studies suggest that apart from genetic factors, maladaptive neuroplasticity, and the repetitive nature of the instrumental technique, psychosocial, psychological, and behavioural factors might also play a role in the onset of MFD. However, the presence of some of these risk factors is supported primarily by anecdotal evidence, with only a few aspects examined empirically. To explore this area further, 14 semi-structured interviews were conducted with a convenience sample of practitioners (8 medical professionals and 6 musician-coaches) who frequently treated MFD sufferers. Throughout their career, these participants are estimated to have interacted with more than 2,000 musicians with MFD, creating a large, indirect sample. A detailed patient profile emerged from the data with three main components: 1) the negative impact of social environments, including traumatic experiences and low quality of instrumental teaching; 2) a perfectionist, anxious, overly sensitive, and acquiescent personality type; and 3) obsessive, controlling, and inadequate practice behaviours. Participants stated MFD needs to be treated holistically and that neglecting these aspects during treatment could jeopardise rehabilitation. Further objective, controlled research trials are needed to describe these factors in detail, quantify their potential impact as risk factors, and understand how they might hinder therapy.

O5-2 Tele-rehabilitation program ‘Funktionstraining-online' in people with Multiple Sclerosis - preliminary results of a first online survey

BackgroundIn 2019, the German Multiple Sclerosis (MS) Society was certified as a provider for ?Funktionstraining? (FT). FT is an exercise training program developed for people with disabilities or people at risk of disability, takes place weekly and is led by a qualified FT-therapist. It is prescribed by a physician (between 12 and 24 months) and is part of outpatient medical rehabilitation. Due to the COVID-19 pandemic, the tele-rehabilitation concept ‘Funktionstraining-online’ (FT-online) was developed for pwMS. This study examines the FT-online from a participants' point of view within an online survey.MethodsWe developed an online questionnaire that included data of sample characteristics, participants' experiences with FT-online in terms of usability and training content. Further, the survey captured the quality of FT-online and the FT-therapist and compared carefully FT-online with face-to-face training. The standardised questionnaires Self-Efficacy Scale - Short Form (ASKU), the Multiple Sclerosis Questionnaire for Physiotherapists MSQPT and the Fatigue-Questionnaire (WeiMuS) were included. The 103 interviewed people with MS (pwMS) participated in FT-online at least for three months.ResultsData analyses are in process. The response rate was 75% (n = 78). The analysed sample is 53.4±8.1 years old with a disease duration of 18±8.7 years (male=7, female=71). Preliminary results in the ASKU certify a low self-efficacy in the sample (2.25 ±0.67). Qualitative results show the advantages for FT-online in the independence of mobility and infrastructure, flexibility, compatibility within job and family, group feeling in times of social distancing and an increase in quality of life. The disadvantages described by the sample are mainly technical problems and lack of socialising. 35% (n = 27) participants experienced both: FT-online and face-to-face. 44.4% (n = 12) of this sample prefer FT-online, 33.3% (n = 9) prefer the face-to-face training course and 22.2% (n = 6) rate both kinds of training equal.ConclusionsThe implementation of FT-online was an important step to ensure the exercise-related physical activity in pwMS during the COVID-19 pandemic. The descriptive analyses show high potential for FT-online training in pwMS. We are aware of the bias in current data, because of the pandemic situation both the free choice of FT-offers and the pandemic circumstances held influence in study outcomes. First results lead to the conclusion that FT-online may be beneficial for a broad range of persons with neurologic diseases, movement disorders and fatigue episodes and should be considered for future medical rehabilitation.

Deep brain stimulation for Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative illness with both motor and nonmotor symptoms. Deep brain stimulation (DBS) is an established safe neurosurgical symptomatic therapy for eligible patients with advanced disease in whom medical treatment fails to provide adequate symptom control and good quality of life, or in whom dopaminergic medications induce severe side effects such as dyskinesias. DBS can be tailored to the patient's symptoms and targeted to various nodes along the basal ganglia-thalamus circuitry, which mediates the various symptoms of the illness; DBS in the thalamus is most efficient for tremors, and DBS in the pallidum most efficient for rigidity and dyskinesias, whereas DBS in the subthalamic nucleus (STN) can treat both tremors, akinesia, rigidity and dyskinesias, and allows for decrease in doses of medications even in patients with advanced stages of the disease, which makes it the preferred target for DBS. However, DBS in the STN assumes that the patient is not too old, with no cognitive decline or relevant depression, and does not exhibit severe and medically resistant axial symptoms such as balance and gait disturbances, and falls. Dysarthria is the most common side effect of DBS, regardless of the brain target. DBS has a long-lasting effect on appendicular symptoms, but with progression of disease, nondopaminergic axial features become less responsive to DBS. DBS for PD is highly specialised; to enable adequate selection and follow-up of patients, DBS requires dedicated multidisciplinary teams of movement disorder neurologists, functional neurosurgeons, specialised DBS nurses and neuropsychologists.

Viewpoint on Milestones for Fellowship Training in Movement Disorders.

Viewpoint on Milestones for Fellowship Training in Movement Disorders.

Cerebellum involvement in dystonia: insights from a spiking neural network model during associative learning.

Dystonia is a neurological movement disorder characterized by twisting and repetitive movements or abnormal fixed postures. This complex brain disease has usually been associated with damages to the Basal Ganglia. However, recent studies point out the potential role of the cerebellum. Indeed, motor learning is impaired in dystonic patients, e.g. during eyeblink classical conditioning, a typical cerebellum-driven associative learning protocol, and rodents with local cerebellar damages exhibit dystonic movements. Alterations in the olivocerebellar circuit connectivity have been identified as a potential neural substrate of dystonia. Here, we investigated this hypothesis through simulations of eyeblink conditioning driven by a realistic spiking model of the cerebellum. The pathological model was generated by decreasing the signal transmission from the Inferior Olive to cerebellar cortex, as observed in animal experiments. The model was able to reproduce a reduced acquisition of eyeblink motor responses, with also an unproper timing. Indeed, this pathway is fundamental to drive cerebellar cortical plasticity, which is the basis of cerebellum-driven motor learning. Exploring different levels of damage, the model predicted the possible amount of underlying impairment associated with the misbehavior observed in patients. Simulations of other debated lesions reported in mouse models of dystonia will be run to investigate the cerebellar involvement in different types of dystonia. Indeed, the eyeblink conditioning phenotype could be used to discriminate between them, identifying specific deficits in the generation of motor responses. Future studies will also include simulations of pharmacological or deep brain stimulation treatments targeting the cerebellum, to predict their impact in improving symptoms.

Movement disorders in COVID-19 times: impact on care in movement disorders and Parkinson disease.

The purpose of this review is to outline the impact of the COVID-19 pandemic on movement disorder holistic care, particularly in the care of people with Parkinson disease (PWP). As the pandemic unfolds, a flurry of literature was published regarding the impact of COVID-19 on people with Parkinson disease including the direct impact of infection, availability of ambulatory care, loss of community-based team care, and acceptability of telemedicine. COVID-19 has impacted the care of PWP in numerous ways. Recognizing infection in PWP poses challenges. Specific long-term complications, including emerging reports of long COVID syndrome is a growing concern. Caregivers and PWP have also been impacted by COVID-19 social isolation restrictions, with radical changes to the structure of social networks and support systems globally. In a matter of weeks, the global community saw an incredible uptake in telemedicine, which brought benefits and pitfalls. As PWP adapted to virtual platforms and the changing architecture of care delivery, the pandemic amplified many preexisting inequities amongst populations and countries, exposing a new 'digital divide'.

Longitudinal Progression of Essential Tremor: Do Tremor Severity Scores Increase at a Uniform Rate?

BackgroundFew longitudinal studies assess the progression of essential tremor (ET). One unexplored issue is whether tremor severity increases across time at a uniform rate. That is, does the observed rate of change in tremor severity within a particular patient remain constant or vary across time? This question of intra-individual differences is particularly important since it reflects a primary patient concern–will the nature of change I have seen to date be what I can expect in the future?MethodsET cases were enrolled in a prospective, longitudinal study. We selected 35 cases and assessed tremor severity via Bain and Findley ratings of Archimedes spirals assigned by a senior movement disorders neurologist. After reviewing both the change in spiral scores and the rate of change in scores, we identified five mutually exclusive patterns of severity change. We calculated the prevalence of each category using two complementary sets of classification criteria.ResultsLength of follow-up was 4.5 to 16.0 years, mean=10.2 years. Mean baseline tremor severity score was 4.6, SD=1.6. Depending upon the classification criteria used, the tremor scores of one-third to one-half of cases did not increase in a uniform fashion but were better described as demonstrating jumps and/or reversals in scores across time.ConclusionsWe document the nature of changes in ET tremor severity scores across a ten-year period via expert ratings of Archimedes spiral drawings. Such natural history data are valuable to patients and clinicians who hope to better understand and predict the likely course of ET symptoms.

The Conundrum of Dystonia in Essential Tremor Patients: How does One Classify these Cases?

Background:The relationship between essential tremor (ET) and dystonia has been long debated and the boundaries between these disorders remain unclear. Here, we highlight the diagnostic uncertainty that can arise when observing dystonic postures in patients who have received ET diagnoses.Methods:An international panel of seven movement disorders neurologists from five countries reviewed the clinical history and videotaped neurological examinations of five individuals diagnosed with ET who also had various features of dystonia on neurological examination. Experts were instructed to assign diagnoses and provide their rationale for diagnostic assignments.Results:The five cases each exhibited a variety of abnormal postures. These were observed by all experts, and interpreted as dystonic postures by six experts. According to six of seven experts, all five cases had ET. One expert classified all cases as dystonic tremor rather than ET. One case had cervical dystonia, and five of seven experts assigned dual diagnoses of ET and dystonia in that case. The assignment of dystonia diagnoses was variable among the other four cases, with two to three experts assigning this diagnosis in each case, underscoring differences in diagnostic interpretation of dystonic postures on examination.Conclusions:This study draws attention to some of the differences between experts in assigning diagnoses of ET or dystonia to individuals with ET and abnormal postures. The goal here was not necessarily to build consensus, but to raise issues, highlight areas of uncertainty, and identify areas of common vs. differentiated thought. Several questions for additional research were also raised.

Towards a Holistic Understanding of Musician's Focal Dystonia: Educational Factors and Mistake Rumination Contribute to the Risk of Developing the Disorder.

Musicians’ Focal Dystonia (MFD) is a task-specific neurological movement disorder, affecting 1–2% of highly skilled musicians. The condition can impair motor function by creating involuntary movements, predominantly in the upper extremities or the embouchure. The pathophysiology of the disorder is not fully understood, and complete recovery is extremely rare. While most of the literature views the condition through a neurological lens, a handful of recent studies point out certain psychological traits and the presence of adverse playing-related experiences and preceding trauma as possible contributors to the onset. The nature and the frequency of these factors, however, are under-researched. The present quasi-experimental study aimed to compare musicians with and without MFD in terms of the frequency of various adverse psychosocial and psychological factors to explore their contribution to the onset of the condition. Professional musicians with MFD (n = 107) and without MFD (n = 68) were recruited from online platforms, musicians’ unions, and organisations to fill out a survey. The survey was based on two previously conducted interview studies and included the Student-Instructor Relationship Scale (SIRS), the Mistake Rumination Scale (MRS), the Trauma History Screen, and self-constructed questions about the received music education, early success, and personal experiences. To identify potential risk factors, independent samples t-tests were conducted and found that there are significant differences in musicians with and without MFD in terms of mistake rumination, early success, and the received music education. A logistic regression showed that six factors contributed to the construct to various extents; we observed a significant model [χ2(80) = 22.681, p < 0.001], which predicted 71.2% of the cases correctly. This exploratory study shows that psychological and psychosocial factors might play a role in the development of MFD. Understanding these in more detail could inform preventative strategies and complement the current therapeutic approaches to support this vulnerable population better.

Enhancing Clinical Information Display to Improve Patient Encounters: Human-Centered Design and Evaluation of the Parkinson Disease-BRIDGE Platform.

BackgroundPeople with Parkinson disease (PD) have a variety of complex medical problems that require detailed review at each clinical encounter for appropriate management. Care of other complex conditions has benefited from digital health solutions that efficiently integrate disparate clinical information. Although various digital approaches have been developed for research and care in PD, no digital solution to personalize and improve communication in a clinical encounter is readily available.ObjectiveWe intend to improve the efficacy and efficiency of clinical encounters with people with PD through the development of a platform (PD-BRIDGE) with personalized clinical information from the electronic health record (EHR) and patient-reported outcome (PRO) data.MethodsUsing human-centered design (HCD) processes, we engaged clinician and patient stakeholders in developing PD-BRIDGE through three phases: an inspiration phase involving focus groups and discussions with people having PD, an ideation phase generating preliminary mock-ups for feedback, and an implementation phase testing the platform. To qualitatively evaluate the platform, movement disorders neurologists and people with PD were sent questionnaires asking about the technical validity, usability, and clinical relevance of PD-BRIDGE after their encounter.ResultsThe HCD process led to a platform with 4 modules. Among these, 3 modules that pulled data from the EHR include a longitudinal module showing motor ratings over time, a display module showing the most recently collected clinical rating scales, and another display module showing relevant laboratory values and diagnoses; the fourth module displays motor symptom fluctuation based on an at-home diary. In the implementation phase, PD-BRIDGE was used in 17 clinical encounters for patients cared for by 1 of 11 movement disorders neurologists. Most patients felt that PD-BRIDGE facilitated communication with their clinician (n=14, 83%) and helped them understand their disease trajectory (n=11, 65%) and their clinician’s recommendations (n=11, 65%). Neurologists felt that PD-BRIDGE improved their ability to understand the patients’ disease course (n=13, 75% of encounters), supported clinical care recommendations (n=15, 87%), and helped them communicate with their patients (n=14, 81%). In terms of improvements, neurologists noted that data in PD-BRIDGE were not exhaustive in 62% (n=11) of the encounters.ConclusionsIntegrating clinically relevant information from EHR and PRO data into a visually efficient platform (PD-BRIDGE) can facilitate clinical encounters with people with PD. Developing new modules with more disparate information could improve these complex encounters even further.

P97/UBXD1 Generate Ubiquitylated Proteins That Are Sequestered into Nuclear Envelope Herniations in Torsin-Deficient Cells.

DYT1 dystonia is a debilitating neurological movement disorder that arises upon Torsin ATPase deficiency. Nuclear envelope (NE) blebs that contain FG-nucleoporins (FG-Nups) and K48-linked ubiquitin are the hallmark phenotype of Torsin manipulation across disease models of DYT1 dystonia. While the aberrant deposition of FG-Nups is caused by defective nuclear pore complex assembly, the source of K48-ubiquitylated proteins inside NE blebs is not known. Here, we demonstrate that the characteristic K48-ubiquitin accumulation inside blebs requires p97 activity. This activity is highly dependent on the p97 adaptor UBXD1. We show that p97 does not significantly depend on the Ufd1/Npl4 heterodimer to generate the K48-ubiquitylated proteins inside blebs, nor does inhibiting translation affect the ubiquitin sequestration in blebs. However, stimulating global ubiquitylation by heat shock greatly increases the amount of K48-ubiquitin sequestered inside blebs. These results suggest that blebs have an extraordinarily high capacity for sequestering ubiquitylated protein generated in a p97-dependent manner. The p97/UBXD1 axis is thus a major factor contributing to cellular DYT1 dystonia pathology and its modulation represents an unexplored potential for therapeutic development.