Motor Neuron Disease

Background: \- Electrical impedance myography (EIM) is a new technique being studied to see if it is helpful in evaluating muscle disorders and nerve disorders. EIM looks at how a mild, painless electrical current travels through muscles. Researchers want to gain experience in using the EIM device. They will collect information on the results of using it on people with and without nerve and muscle diseases, and compare that with information from other standard tests. First, they will test the device on healthy people. Then they will test people with a variety of neuromuscular diseases. Because the test is noninvasive and not painful, researchers will test both children and adults. Objectives: \- To gain experience using the EIM muscle testing device. Eligibility: * Healthy volunteers at least 2 years old. * Individuals at least 2 years old who have neuromuscular disease. Design: * Participants will be screened with a medical history and physical exam. * Participants will have one 2-3 hour clinic visit. Researchers may request follow-up visits. * Participants will be tested with the EIM device. The device and small electrodes will be placed on their skin. An electric current will pass through the device, but the participants will not feel this. * Participants may have an ultrasound test. A gel will be put on their skin, and a device will be moved over the skin. * Participants may have a nerve test. Electrodes will be placed on their skin, and they will feel a small shock. * Participants may have a test where a thin needle is inserted in their muscle.

Functional Outcomes and Control Using Synchron BCI - Australia (FOCUS-AUS)

INdependence Through Endovascular Neuroprosthetic Technology (INTENT): an Early Feasibility Study

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.

Functional Outcomes and Control Using Synchron BCI - Canada (FOCUS-CAN)

This study is designed to learn more about the natural history of inherited neurological disorders and the role of heredity in their development. It will examine the genetics, symptoms, disease progression, treatment, and psychological and behavioral impact of diseases in the following categories: hereditary peripheral neuropathies; hereditary myopathies; muscular dystrophies; hereditary motor neuron disorders; mitochondrial myopathies; hereditary neurocognitive disorders; inherited neurological disorders without known diagnosis; and others. Many of these diseases, which affect the brain, spinal cord, muscles, and nerves, are rare and poorly understood. Children and adults of all ages with various inherited neurological disorders may be eligible for this study. Participants will undergo a detailed medical and family history, and a family tree will be drawn. They will also have a physical and neurological examination that may include blood test and urine tests, an EEG (brain wave recordings), psychological tests, and speech and language and rehabilitation evaluations. A blood sample or skin biopsy may be taken for genetic testing. Depending on the individual patient s symptoms, imaging tests such as X-rays, CT or MRI scans and muscle and nerve testing may also be done. Information from this study may provide a better understanding of the genetic underpinnings of these disorders, contributing to improved diagnosis, treatment, and genetic counseling, and perhaps leading to additional studies in these areas.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease in which motor neuron cells of the brain and spinal cord progressively degenerate and die. There is currently a lack of curative treatment for individuals that are diagnosed with ALS. Since treatment options are limited, researchers have placed greater emphasis on evaluating Quality-of-Life (QoL) as it offers perspective into the everyday life of the patient and is sensitive to changes over time. The goal of this longitudinal observational study is to learn more about what factors negatively impact an individual's QoL after they are diagnosed with ALS. Previous research has shown that an individual's level of physical functioning can negatively impact their quality of life, but this may not be the only factor. The main objectives this study are: 1. Assess if there is a statistically significant correlation between patient's functionality scores (ALSFRS-R) and quality of life scores (ALSAQ-40). 2. Determine how disease stage (King's Clinical Severity Staging System) affects correlation between functionality scores (ALSFRS-R) and quality of life scores (ALSAQ-40). Participants will complete a quality-of-life questionnaire (ALSAQ-40) every other time they present to their standard-of-care clinic visits for a period of two years. In parallel, with the functionality rating (ALSFRS-R) scores captured as standard-of-care at every clinic visit.

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.

Background: SBMA is an inherited chronic disease. It affects males in mid to late adulthood. It causes slowly progressive weakness of muscles and hand tremors. Researchers want to learn more about the effects of SBMA. Objective: To identify measurements that change over time in SBMA, including tests of muscle strength and function, as well as measurements of muscle and fat size. Eligibility: Men over the age of 18 both with and without a history of SBMA. Design: Participants will have a medical history, physical exam, and blood and urine tests. They will have neuromuscular ultrasound. They will have a lumbar puncture to obtain spinal fluid. For this, a needle will be inserted into the spinal canal in the lower back. Participants will have muscle strength and function tests. These tests may include pushing, pulling, rising from a chair and sitting back down, and/or walking. During these tests, they may wear an accelerometer (activity tracker) on their wrist. Participants will get an activity tracker to wear on their wrist for 10 days at home every 3 months. Participants with SBMA will also have lower limb magnetic resonance imaging (MRI) and optional whole-body MRI. They will have lung function tests. They will have speech and swallow tests. They will complete questionnaires. They may have optional body scans to measure bone density and lean body mass. They may have optional muscle biopsies. For biopsies, a needle will be used to take a small piece of muscle from the leg. Participants with SBMA will have 5 study visits over 2 years (every 6 months). Participants without SBMA will have 1 study visit.

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.

Many people living with neurodegenerative conditions like dementia, motor neuron disease (MND), multiple sclerosis (MS), and Parkinson's disease (PD), suffer from speech problems. Using common digital technologies such as smartphone apps, the investigators can record and analyse speech in detail to provide new information for people living with these conditions, researchers, and healthcare professionals. This study will investigate the use of these digital speech recordings to help diagnose and monitor these conditions. To take part, participants will have either a diagnosis of dementia, motor neuron disease, Parkinson's disease or Multiple Sclerosis, OR they will have no diagnosis of a neurological condition. Researchers will compare people with a diagnosis of a Neurological condition to those without.

Amyotrophic lateral sclerosis (ALS) is a serious rapidly progressive disease of the nervous system. The average survival from the time of diagnosis is two to three years. The patient physical and psychological sufferings in ALS are immense, and apart from Riluzole, there is no effective treatment. Care of advanced ALS have an estimated cost of 4-8 million NOK per year. Perhaps the most challenging topic of ALS care is the decision to extend ventilation support into the stages of disease that require treatment both during day and night. In these cases, treatment is clearly life-sustaining and although quality of life may be maintained, the burden of caregiving imposed upon family or health care workers is huge, regardless of tracheostomy (TIV) or non-invasive (NIV) modality. The present study is a longitudinal questionnaire study in Norway measuring overall quality of life, health-related quality of life, and disease-specific quality of life in ALS patients, partners and children before and after the introduction of life sustaining ventilation support. The investigators aim to increase the knowledge on how life-sustaining ventilation support with NIV or TIV affects the quality of life in ALS patients, life partners and children. The results from the study may provide crucial information for clinicians and patients on one of the most difficult ethical issues of ALS treatment. The investigators anticipate that this information will facilitate a shared decision making processes, weighing benefits and disadvantages in a wider perspective.

The GB-PRIME Study is an early feasibility study designed to assess the clinical safety and functionality of the Neuralink N1 Implant and R1 Robot. This study involves participants who have tetraparesis, tetraplegia, or a diagnosis that may lead to these conditions. The N1 Implant is a wireless, rechargeable device mounted on the skull, connected to electrode threads that are inserted into the brain by the R1 Robot, which is a robotic device specifically designed for this procedure.

The purpose of this study is to investigate the safety and tolerability of intrathecal riluzole in adults with amyotrophic lateral sclerosis.

The UAE-PRIME Study is a feasibility study designed to assess the initial clinical safety and functionality of the Neuralink N1 Implant and R1 Robot. This study involves participants who have tetraparesis, tetraplegia, or a diagnosis that may lead to these conditions. The N1 Implant is a wireless, rechargeable device mounted on the skull, connected to electrode threads that are inserted into the brain by the R1 Robot, which is a robotic device specifically designed for this procedure.

The goal of this observational study is to understand the clinical variability in a population of ALS patients using multidimensional biomarkers. The main questions it aims to answer are: * Which set of biomarkers explain genotypic-phenotypic correlations in ALS? * Which set of biomarkers can be used to subdivide the ALS population in homogeneous subgroups? Participants will undergo: * neurological evaluation * neurophysiological evaluation * neuropsychological evaluation * whole exome sequencing * biomarker measurement in CSF and plasma

Study Description: Characterization of Motor Neuron Disease Phenotypes The goal of this observational study is to understand the clinical presentation of motor neuron disease (MND) in patients attending the Neurology Department of the Istituto Auxologico Italiano. The main questions it aims to answer are: * What are the specific clinical phenotypes associated with MND? * How can these phenotypes contribute to a better understanding of the disease's underlying mechanisms and improve prognostic accuracy? Participants will undergo: * Clinical evaluation using validated scales * Neurophysiological and neuroradiological instrumental assessment * Neuropsychological evaluation * Collection of biological materials for genetic screening and biomarker assessment, if necessary.

This is a non-interventional observational study designed to systematically record the results of routine laryngeal examinations and specific characteristics of dysphagia in patients with neurodegenerative disorders. The results of a fiberoptic / flexible endoscopic evaluation of swallowing (FEES) while performing a structured task protocol will be recorded. If available, laryngeal electromyography (EMG) results will also be recorded. In addition to the examination results, demographic and disease-specific data are collected, and two questionnaires, the Swallowing Disturbance Questionnaire for Parkinson's Disease (SDQ-PD) and the swallowing specific Quality Of Life Questionnaire (SWALQOL), are administered.

The goal of this natural history study is to learn more about the biological and clinical aspects of amyotrophic lateral sclerosis (ALS). This study's findings will help with drug discovery, biomarker discovery, and outcome measure validation. Adults living with ALS, other motor neuron diseases (MND), a known mutation related to ALS and healthy volunteers contribute prospective and retrospective data to this study remotely. The study is sponsored and conducted by the ALS Therapy Development Institute.

STUDY OVERVIEW Brain injury can result in a loss of consciousness or awareness, to varying degrees. Some injuries are mild and cause relatively minor changes in consciousness. However, in severe cases a person can be left in a state where they are "awake" but unaware, which is called unresponsive wakefulness syndrome (UWS, previously known as a vegetative state). Up to 43% of patients with a UWS diagnosis, regain some conscious awareness, and are then reclassified as minimally conscious after further assessment by clinical experts. Many of those in the minimally conscious state (MCS) and all with unresponsive wakefulness syndrome (UWS) are incapable of providing any, or consistent, overt motor responses and therefore, in some cases, existing measures of consciousness are not able to provide an accurate assessment. Furthermore, patients with locked-in syndrome (LIS), which is not a disorder of consciousness as patients are wholly aware, also, struggle to produce overt motor responses due to paralysis and anarthria, leading to long delays in accurate diagnoses using current measures to determine levels of consciousness and awareness. There is evidence that LIS patients, and a subset of patients with prolonged disorders of consciousness (DoC), can imagine movement (such as imagining lifting a heavy weight with their right arm) when given instructions presented either auditorily or visually - and the pattern of brain activity that they produce when imagining these movements, can be recorded using a method known as electroencephalography (or EEG). With these findings, the investigators have gathered evidence that EEG-based bedside detection of conscious awareness is possible using Brain- Computer Interface (BCI) technology - whereby a computer programme translates information from the users EEG-recorded patterns of activity, to computer commands that allow the user to interact via a user interface. The BCI system for the current study employs three possible imagined movement combinations for a two-class movement classification; left- vs right-arm, right-arm vs feet, and left-arm vs feet. Participants are trained, using real-time feedback on their performance, to use one of these combinations of imagined movement to respond to 'yes' or 'no' answer questions in the Q\&A sessions, by imagining one movement for 'yes' and the other for 'no'. A single combination of movements is chosen for each participant at the outset, and this participant-specific combination is used throughout their sessions. The study comprises three phases. The assessment Phase I (sessions 1-2) is to determine if the patient can imagine movements and produce detectable modulation in sensorimotor rhythms and thus is responding to instructions. Phase II (sessions 3-6) involves motor-imagery (MI) -BCI training with neurofeedback to facilitate learning of brain activity modulation; Phase III (sessions 7-10) assesses patients' MI-BCI response to closed questions, categorized to assess biographical, numerical, logical, and situational awareness. The present study augments the evidence of the efficacy for EEG-based BCI technology as an objective movement-independent diagnostic tool for the assessment of, and distinction between, PDoC and LIS patients.

The proposed study is an Open-Label, Single-Dose Study to Assess the Safety, and Pharmacodynamics (PD) signals of MRG-001 in Patients with Amyotrophic Lateral Sclerosis (ALS). MRG-001 will be administered subcutaneously 3 times per week for 2 weeks. This cycle will be repeated for 3 months. In total, patients are expected to receive 18 injections over the span of 3 months.

The goal of this observational study is to learn about the emotional perception in people with ALS disease compared to people with other neuromuscular disease and healthy controls. The main questions it aims to answer are: * How people with ALS judge happy and angry faces and what their "insight" into these judgements are like * How their autonomic responses differ from the other two test group Participants will asked to judge if a face presents a happy emotion or angry emotion. Researchers will compare the ALS group responses with neuromuscular diseases group and healthy control group responses to see if the ALS group judge more happy faces than angry.

The investigators hypothesize a relevant impact of cognitive status over gait performance in patients with amyotrophic lateral sclerosis (ALS), contributing to poor mobility and representing a relevant risk for falls. The present observational, cross-sectional study on ambulatory patients with ALS will evaluate gait performance using different sets of dual-task conditions to demonstrate the importance of cognitive aspects in rehabilitation programs for these patients. The dual-task conditions to be assessed during gait performance will include: counting backwards by 3 (executive simple task); counting backwards by 7 (executive complex task); mnemonic recall of the Rey's Auditory Verbal Learning Test (RAVLT). Patients' performance will be compared with a group of healthy controls with similar age and sex distribution in order to highlight the specific effects of the disease.

Amyotrophic Lateral Sclerosis (ALS) is an aggressive, deadly disease. ALS leads to destruction of the neural pathways which control the conscious movements of the muscles. This destruction leads to muscular dystrophy with increasing difficulties in moving, breathing, swallowing, and speaking. In the last phase of an ALS patient's life it is necessary with respiratory therapy in order to breathe. In average an ALS patient lives 3 years from the time he or she gets the diagnose. The cause of the disease is still unknown and there is currently no treatment which can stop the progression of the disease. Former clinical studies have indicated that the innate immune system and in particular the complement system plays a significant role in the progression of ALS. The complement system, which is activated in cascades, is part of the innate system but participates in the innate as well as the acquired immune system. Former clinical trials have been characterized by limited knowledge about both the complement system as well as to how it is measured. Today it is possible to measure directly on the different components of the complement system and to understand its contribution to the overall immune response. It is also possible today to detect defects of the complement system. All these progressions are the foundation for this project which is carried out in close cooperation with one of the world's leading researchers in the complement system, professor Peter Garred from Rigshospitalet. The aim is to make a national research project about ALS in order to investigate the role of the innate immune system, and especially the complement system, in patients with ALS. In the long term the hope is, that this will lead the way to a targeted and effective medical treatment to the people affected by this grave disease.