Movement Disorders

The objective of this study is to compile real-world outcomes of Boston Scientific commercially approved radiofrequency (RF) ablation systems used in the central nervous system (CNS) for use in functional neurosurgery.

The goal of this clinical trial is to explore the effects of cerebellar nuclei TIS stimulation on improving tremor and gait disorders in PD patients. Through randomized double-blind grouping, the differences in efficacy between TIS intervention and sham stimulation intervention for tremor and gait disorders in PD patients will be compared.

The proposed two-arm randomized waitlist-controlled trial will use a mixed-methods design to investigate the effects of dyadic mindfulness on physio-psycho-spiritual outcomes in people with Parkinson's Disease (PwPD) and their family caregivers. One hundred Chinese patient-caregiver dyads will be randomized to receive eight weekly 90-minute dyadic mindfulness sessions or usual care. Outcome measures include negative emotions (primary outcome), patient-caregiver relationship, mindfulness, HRQOL, gut microbiome, PD-related symptoms, and caregiving burden. An actor-partner interdependence model will be used to explore the interactions of treatment effects within the dyads. The dyads will be assessed at baseline(T0), post-intervention(T1), and 4-months post-intervention(T2). The investigators will also invite 25 dyads to attend in-depth interviews exploring their experiences, perceived changes, and factors attributable to the effectiveness/ineffectiveness of the intervention. Generalized linear mixed-effects (GLME) with intention-to-treat analysis will be used to compare the changes in outcomes over time within and between the two arms. The findings will be triangulated to provide a comprehensive evaluation of the intervention's effectiveness. This study will generate rigorous scientific evidence to inform the application of dyadic mindfulness as a public health practice preventing the progression of psychological distress in PwPD and caregivers to clinically severe levels. Its self-help nature also enriches the primary care for this clinical cohort.

This research study aims to identify MRI-based brain biomarkers that predict an individual's response to Deep Brain Stimulation (DBS). In particular, this study will focus on changes in cognition associated with DBS. A total of 55 participants with Parkinson's Disease planning to undergo DBS will be recruited from MUSCs Clinical DBS Program. Participants will undergo four visits, including a 1-hour screening visit, a 1.5-hour pre-DBS MRI scanning visit, and a 3.5-hour post-DBS cognitive assessment visit. In addition control participants without Parkinson's Disease will be recruited to undergo MRI scanning and cognitive assessments.

Dystonia is a motor disorder caused by involuntary, intermittent, or sustained muscle contractions, leading to abnormal movements or postures. It can affect any body region and often results in significant functional disability and healthcare burden. Although its familial nature was recognized early on, the advent of high-throughput DNA sequencing has dramatically increased the identification of dystonia-associated genes. Dystonia now encompasses all modes of inheritance-autosomal dominant (e.g., TOR1A, KMT2B), autosomal recessive, X-linked, and mitochondrial-and over 100 genes have been implicated. Many forms involve structural variants (SVs) or copy number variations (CNVs), which are challenging to detect using standard short-read sequencing (srWGS). Molecular diagnosis is essential, ending the diagnostic odyssey and enabling genetic counseling, prognosis, reproductive planning, and-in some cases-targeted therapies. For instance, GNAO1-related dystonia may respond to deep brain stimulation, while dopa-responsive dystonia benefits from levodopa. Despite advances, srWGS has key limitations, especially for detecting repeat expansions, SVs, and phasing alleles. This likely explains the low diagnostic yield in dystonia compared to other neurological disorders, with over 70% of cases remaining unsolved. Long-read sequencing (lrWGS), such as Oxford Nanopore technology, overcomes many of these challenges by reading native DNA fragments thousands of bases long. It enables comprehensive detection of SNVs, indels, SVs, CNVs, methylation changes, and repeat expansions-including known and newly discovered pathogenic expansions (e.g., in NOTCH2NLC). It also allows phasing without parental samples, which is crucial in recessive cases. The investigators propose that lrWGS could significantly increase the diagnostic yield in dystonia, improving patient care, enabling appropriate genetic counseling, and paving the way for personalized treatment strategies.

The purpose of this study is to validate previously developed physical function-clustered specific machine-learned accelerometer algorithms to estimate total daily energy expenditure (TDEE) in individuals with general movement and functional limitations.

Injuries affecting the central nervous system may disrupt the cortical pathways to muscles causing loss of motor control. Nevertheless, the brain still exhibits sensorimotor rhythms (SMRs) during movement intents or motor imagery (MI), which is the mental rehearsal of the kinesthetics of a movement without actually performing it. Brain-computer interfaces (BCIs) can decode SMRs to control assistive devices and promote functional recovery. Despite rapid advancements in non-invasive BCI systems based on EEG, two persistent challenges remain: First, the instability of SMR patterns due to the non-stationarity of neural signals, which may significantly degrade BCI performance over days and hamper the effectiveness of BCI-based rehabilitation. Second, differentiating MI patterns corresponding to fine hand movements of the same limb is still difficult due to the low spatial resolution of EEG. To address the first challenge, subjects usually learn to elicit reliable SMR and improve BCI control through longitudinal training, so a fundamental question is how to accelerate subject training building upon the SMR neurophysiology. In this study, the investigators hypothesize that conditioning the brain with transcutaneous electrical spinal stimulation, which reportedly induces cortical inhibition, would constrain the neural dynamics and promote focal and strong SMR modulations in subsequent MI-based BCI training sessions - leading to accelerated BCI training. To address the second challenge, the investigators hypothesize that neuromuscular electrical stimulation (NMES) applied contingent to the voluntary activation of the primary motor cortex through MI can help differentiate patterns of activity associated with different hand movements of the same limb by consistently recruiting the separate neural pathways associated with each of the movements within a closed-loop BCI setup. The investigators study the neuroplastic changes associated with training with the two stimulation modalities.

This registry is a prospective, multicenter, international, single arm, observational post-approval registry with follow-up at 3, 6, and 12 months, and annually for 5 years. The proposed registry will enroll 60 subjects and will be conducted at approximately 10 centers worldwide.

There is limited data on outcomes for children who have undergone deep brain stimulation (DBS) for movement disorders, and individual centers performing this surgery often lack sufficient cases to power research studies adequately. This study aims to develop a multicenter pediatric DBS registry that allows multiple sites to share clinical pediatric DBS data. The primary goals are to enable large-scale, well-powered analyses of the safety and efficacy of DBS in the pediatric population and to further explore and refine DBS as a therapeutic option for children with dystonia and other hyperkinetic movement disorders. Given the current scarcity of evidence available to clinicians, this centralized multicenter repository of clinical data is critical for addressing key research questions and improving clinical practice for pediatric DBS.

The Epilepsy-Dyskinesia Study aims to advance the understanding of the clinical and molecular spectrum of epilepsy-dyskinesia syndromes, monogenic diseases that cause both movement disorders and epilepsy. Addressing challenges in rare disease research -such as small, geographically dispersed patient populations and a lack of standardized protocols- the study employs a multinational retrospective survey endorsed by the International Parkinson and Movement Disorder Society. This survey seeks to collect comprehensive data on clinical features, disease progression, age of onset, genetic variants, and concurrent neurological conditions, standardizing data collection across countries to provide a unified understanding of these conditions. Through retrospective review and molecular data analysis, the study aims to identify patterns and correlations between movement and seizure disorders, uncovering genotype-phenotype relationships. The initiative\'s goals are to enhance understanding of epilepsy-dyskinesia syndromes, inform precision medicine approaches, and foster international collaboration.

The purpose of the HSP Sequencing Initiative is to better understand the role of genetics in hereditary spastic paraplegia (HSP) and related disorders. The HSPs are a group of more than 80 inherited neurological diseases that share the common feature of progressive spasticity. Collectively, the HSPs present the most common cause of inherited spasticity and associated disability, with a combined prevalence of 2-5 cases per 100,000 individuals worldwide. In childhood-onset forms, initial symptoms are often non-specific and many children may not receive a diagnosis until progressive features are recognized, often leading to a significant diagnostic delay. Genetic testing in children with spastic paraplegia is not yet standard practice. In this study, the investigators hope to identify genetic factors related to HSP. By identifying different genetic factors, the investigators hope that over time we can develop better treatments for sub-categories of HSP based on cause.

The purpose of this study is to investigate the brain activity associated with motor and non-motor symptoms of movement disorders, including Parkinson's disease (PD) and essential tremor. These movement disorders commonly have significant non-motor features, such as depression, cognitive and memory impairment, decreased attention, speech and language disturbances, and slower processing speeds. The investigators are interested in the brain activity associated with these motor and non-motor symptoms, and propose to investigate changes in brain activity while the investigators perform recordings of the surface and deep structures of the brain, in addition to the typical recordings the investigators perform, during routine deep brain stimulation (DBS) surgery.

The research study is being conducted to better understand parts of the human brain called the cortex, basal ganglia, thalamus, and cerebellum in patients with movement disorders (such as Parkinson's disease, essential tremor, dystonia, or ataxia). These brain structures are involved in movement disorders. This study attempts to better understand the brain electrical activity associated with these disorders, both in patients with and without deep brain stimulation (DBS). Recordings are made from the scalp with a noninvasive electrode and/or through the DBS stimulator if the participant has a stimulator model that is able to sense brain activity. These recordings are analyzed along with measures of movement disorder symptoms to identify brain signal signatures of symptoms.

The purpose of this research study is to develop a protocol using a fully wearable, portable lower-limb exoskeleton for improving leg and walking function in people with movement disorders. The study investigates the effects of wearing the device during a set of experiments including leg stretching, treadmill walking and overground walking in muscle activity, joint motion, and gait performance. The goal is to develop an effective lower-limb strategy to restore lost leg function (e.g., range of motion) and gait ability, and improve quality of life in people with movement deficits following a neurological disorder.

Veterans with mid to later stage Parkinson's disease (PD) may not be able to work out as hard as they need to, to prevent brain cell loss. Maybe they could work out longer and more frequently to make up for this during their good times and good weeks and then rest during the bad weeks. The investigators will compare how effective working out a lot one week per month with a break of three weeks is to continuously exercising weekly with no breaks in people with mid stage PD. The investigators will look at how fast participants walk per minute, whether they become more physically active, the biochemicals in their blood, and at how stiff their blood vessels are before and after the exercise.

The purpose of this international study is to evaluate long-term safety and effectiveness of Abbott deep brain stimulation (DBS) systems for all indications, including Parkinson's disease, essential tremor or other disabling tremor and dystonia.

Participants will perform experiments with non-invasive activity recordings. The study will record from multiple non-invasive signal sources that reflect motor intent that may include: electroencephalography (EEG), electromyography (EMG), functional near infrared spectroscopy (fNIRS), inertial measurement units (IMUs), eye movements, pupil size, and speech. Participants will wear all or a subset of these sensors and be asked to perform, imagine, or attempt movements or speech. The recorded sensor signals will be decoded to help guide an end effector, which may be a computer, robotic arm, wheelchair, or other assistive device. These experiments present minimal risk and participants may withdraw participation at any time for any reason. Participants may return for additional experiments if desired and to perform additional comparisons. If a participant withdraws during a comparison, another participant will be recruited to complete collection of data for that comparison.

The goal of the study is to generate a biorepository of longitudinal biofluids-blood (plasma and serum), cerebral spinal fluid (CSF) and urine linked to genetics and longitudinal clinical information that are made available to the research community. To accomplish these goals, we will enroll 800 Amyotrophic Lateral Sclerosis (ALS) patients and 200 healthy controls from sites globally, over a 5 year time frame. Additionally, speech and motor function and spirometry measures will be collected bi-weekly in a subset of participants. ALS participants will be asked to come to the clinic for 5 study visits approximately every 4 months. Healthy participants will be coming for 2 study visits with a 12-month interval between visits. These samples and clinical information will be stored in a de-identified manner and made available for investigators to use in future research studies.

This study, through different administration methods, adopted a randomized, double-blind, placebo-controlled trial design to evaluate the safety and tolerability of human umbilical cord mesenchymal stem cells (hUC-MSCs) in patients with Parkinson's disease, explore their initial effectiveness and the relationship between biological active factors and therapeutic efficacy. The "Clinical Study on the Treatment of Parkinson's Disease with Human Umbilical Cord Mesenchymal Stem Cells" of this study is expected to provide clinical trial evidence for the development of safe and effective clinical cell therapies for patients with Parkinson's disease.

The Registry and Natural History of Epilepsy-Dyskinesia Syndromes is focused on gathering longitudinal clinical data as well as biological samples (blood, urine, and/or skin/tissue) from male and female patients, of all ages, who have a genetic diagnosis of epilepsy-dyskinesia syndromes. Through prospective review and molecular data analysis, the study aims to identify patterns and correlations between movement and seizure disorders, uncovering genotype-phenotype relationships. The initiative's goals are to enhance understanding of epilepsy-dyskinesia syndromes, inform precision medicine approaches, and foster international collaboration.

A variety of antineuronal antibodies have been detected in the cerebrospinal fluid (CSF) of patients with neurological diseases. This raises the question of whether these antibodies are disease-specific or merely an epiphenomenon of inflammatory processes in the brain. The registry was established with the following objectives: \[1\] Are antineuronal antibodies much more common than previously thought in various neurological disorders for which the etiology has not yet been elucidated? \[2\] Can further correlations, such as those between HSV infection and NMDA receptor autoimmunity, be identified? \[3\] Are these antibodies mainly non-specific epiphenomena or are they crucial for the pathogenesis? \[4\] What is the clinical course of patients with antineuronal antibodies and their response to therapy? These questions will be addressed in a broad immunohistological screening of a large number of CSF samples and a clinical database of patients with neurological disorders.

Safety and Efficacy of AAV9/AP4B1 For Patients with AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47): A Phase 1/2 Single-Center, Open-Label Study of Stereotactic Intra-cisterna Magna Administration. The goal of this clinical trial is to evaluate whether a gene therapy can safely treat children with SPG47, a rare genetic condition that causes progressive spasticity and developmental delays. The main questions it aims to answer are: * Is the gene therapy safe and well tolerated? * Does the gene therapy improve motor function and developmental outcomes? Participants will: * Undergo screening assessments to confirm eligibility * Receive a single dose of the gene therapy vector * Attend follow-up visits for safety monitoring and developmental assessments over the course of five years

The aim of this study is to investigate whether a smartphone app can increase physical activity in patients with Parkinson's Disease in daily life for a long period of time (12 months).

Medically intractable tremors are a common difficult clinical situation. Deep brain stimulation decreases Parkinson's disease tremor and essential tremor, but not all patients are candidates from a diagnostic, medical, or social standpoint, prompting the need for alternative surgical strategies. Less invasive lesional brain surgery (thalamotomy) procedures by radio-surgery or MRI-guided focused ultrasound have emerged and have proven to be effective in these third-line indications. Recently, a new technology has emerged allowing the performance of minimally invasive lesion surgeries by MRI-Guided Laser Interstitial Thermal Therapy (MRIg-LITT). MRIg-LITT has been shown to be effective and safe in management of epilepsies and brain tumors. However, no study has evaluated MRIg-LITT for performing thalamotomy in medically intractable tremor.In a pilot study, the investigators propose to evaluate the effect and safety of unilateral thalamotomy by MRIg-LITT in the management of medically intractable tremor of parkinsonian or essential origin.

Movement disorders are a group of neurological conditions that cause problems with movement, either in the form of excessive, reduced, or slow movements. Some commonly known movement disorders include Parkinson disease, dystonia, ataxia, and Tourette syndrome. Multiple movement disorders have unique handwriting characteristics that can be measured using an inkless pen and a digitalized tablet. Handwriting is a complex skill that requires a combination of cognition, motor planning, and visuomotor integration. Handwriting deteriorates in patients with neurodegenerative diseases. This study aims to discern variations in the kinematics (movement patterns) involved in handwriting between individuals with movement disorders and healthy controls. Participants will be invited to carry out a series of handwriting tasks. The pen motions will be captured using an inkless pen and a digitizing tablet linked to a laptop. The entire set of tasks is designed to be completed within 30 minutes. The data will then be collected, processed, and analyzed utilizing a handwriting analysis software.