Primary Lateral Sclerosis

Researchers are studying hereditary spastic paraplegia (HSP), a group of disorders causing progressive stiffness and weakness in the legs. This study explores how continuous infusion of intrathecal baclofen (ITB), delivered via a surgical pump, compares to oral baclofen for treating spasticity in HSP patients. The trial aims to find the best time to start ITB treatment and understand differences in response among various HSP types. It is a prospective, open-label study conducted over three years in China with 50 participants aged 14 to 70 years. Participants are divided into two groups: one receiving ITB through surgery, and the other receiving oral baclofen if they decline or do not respond well to ITB testing. Both groups undergo professional assessments every six months. The study will monitor changes in walking ability, muscle tone, joint movement, quality of life, pain, mental health, cognition, and complications. It also examines how ITB affects skeletal deformities and compares outcomes between genetic subtypes and simple versus complex HSP. Throughout the study, patients will be evaluated regularly at 6, 12, 18, 24, 30, and 36 months after treatment begins. Assessments include the Six-Minute Walk Test, step length, walking speed, knee flexion angle, Modified Ashworth Scale, joint range of motion, and various scales measuring disability, pain, cognition, depression, anxiety, and spasticity. Researchers will also track complications and deformity changes. This comprehensive monitoring helps assess the safety and effectiveness of ITB over time and aims to improve care for HSP patients.

Researchers are conducting a prospective cohort study to assess the long-term benefits and risks of surgical treatments for foot deformities caused by hereditary spastic paraparesis (HSP). This condition involves nerve degeneration leading to foot problems such as equinovarus, cavus foot, and Achilles tendon contracture, which affect walking and quality of life. The study aims to understand the effectiveness of surgery, the best timing for these procedures, and to develop clear criteria for treatment decisions. The study will enroll 100 patients aged 10 to 45 years with confirmed HSP and progressive foot deformities that have not improved with standard treatments like medication or rehabilitation exercises. All participants will undergo surgical correction of their foot deformities and be followed for two years. The research will focus on the surgical outcomes and aim to optimize timing and evaluation methods for these interventions. Participants will have regular clinical evaluations over a two-year period to monitor their progress. These assessments include scoring systems for foot and ankle function, pain levels, foot posture, walking ability, spasticity severity, and motor function. Observations will be made at 1, 3, 6, 12, 18, and 24 months after treatment to track changes and safety. The study will provide detailed information on how surgery impacts walking, pain, and overall function in HSP patients.

Researchers are collecting data in a natural history study focusing on ALS and other motor neuron disorders (MND) such as Primary Lateral Sclerosis, Kennedy Disease, Progressive Muscular Atrophy, and Progressive Bulbar Palsy. The study aims to build a comprehensive data repository capturing clinical information and disease progression from patients attending participating clinical sites. The research platform, NeuroBANK, supports linking clinical data with biological samples and imaging information from multiple studies. Participants diagnosed with ALS or other MNDs provide baseline data including demographics, disease history, and family history. During each clinical visit, sites collect disease-specific outcomes and events over time, which are entered into NeuroBANK. The study allows collection of additional biomarker and outcome data through over 20 extra forms. Data collected are anonymized and shared with medical researchers via a controlled license. Participants are asked for consent during routine clinical visits, after which they receive a unique identifier to link their data across studies. The study involves regular follow-ups every 3 to 4 months for up to 5 years, including assessments like ALS Functional Rating Scale-Revised, lung function, survival tracking, neurological exams, and physical tests. Data quality is monitored, and biological samples and imaging studies may also be collected and linked within the platform. The total participation duration can last up to five years with ongoing data collection.

Hereditary Spastic Paraplegia type 56 (SPG56) is a complex early-onset form of HSP caused by genetic mutations in the CYP2U1 gene. Currently, there is no standardized treatment for SPG56. This research aims to evaluate the safety and potential benefits of calcium folinate in SPG56 patients through a prospective, open-label, single-arm clinical trial sponsored by Shanghai 6th People's Hospital. Participants will receive calcium folinate treatment in two phases. Initially, calcium folinate is given intravenously for 5 consecutive days at 1 mg/kg/day in two divided doses. Following this, during hospitalization, treatment switches to oral calcium folinate at 2 mg/kg/day. Afterward, long-term oral calcium folinate at the same dose is continued. The trial will last for six years with a total of 10 participants. During the study, patients will undergo regular professional clinical evaluations. Researchers will measure outcomes such as the Gross Motor Function Measure (GMFM-88) after five years of follow-up. Additional assessments include the Spastic Paraplegia Rating Scale (SPRS), Mini-Mental State Examination (MMSE), laboratory tests, brain imaging (CT/MRI), gait analysis, Montreal Cognitive Assessment (MoCA), and high-density electroencephalogram at the five-year mark. Safety and compliance will also be monitored throughout the study period.

Researchers are studying amyotrophic lateral sclerosis (ALS) and related disorders to better understand the natural history of these diseases. This observational study collects and analyzes clinical information from patients receiving care at centers using a specific electronic health record system. The goal is to gather standardized data to support ALS research and improve knowledge about the disease progression and characteristics. Participants include patients diagnosed with ALS or related disorders such as primary lateral sclerosis and progressive muscular atrophy. The study uses data collected through the Epic electronic health record system at clinical centers in the CReATe consortium. There are no investigational treatments or interventions; instead, the study focuses on gathering information systematically over time. During the study, researchers will use the ALS Toolkit to collect and utilize electronic health record data for up to 12 months. Participants will provide consent to allow access to their medical records, and the study team will analyze this information to track disease progression and related outcomes. Participants are expected to be those receiving care at participating centers, and the study involves no additional treatment procedures or interventions beyond usual care.

Researchers are conducting a long-term observational study called CAPTURE ALS to collect detailed information about Amyotrophic Lateral Sclerosis (ALS) and related neurodegenerative disorders. This platform aims to gather and store a wide range of data and biological samples to support future ALS research worldwide. The study includes participants with ALS, related disorders, and healthy controls for comparison to better understand disease progression over time. Participants with ALS or related conditions will attend up to five in-person visits over one year at screening, and at 0, 4, 8, and 12 months. Healthy control participants will have three visits at screening, 0, and 8 months. At each visit after screening, all participants will undergo MRI scans, cognitive and speech assessments, and complete health questionnaires. Those with ALS will also have clinical evaluations specific to their condition, including neurological exams and lung function tests. Biospecimens such as blood, saliva, and optionally cerebrospinal fluid will be collected. During the study, researchers will monitor various outcomes including ALS functional rating, lung capacity, speech ability, neurological function, brain imaging results, cognitive and behavioral screening, quality of life, and ALS-specific questionnaires. These measurements occur every four months over the year. The study collects comprehensive data to understand the progression of ALS and related disorders, with safety and participant well-being monitored throughout the participation period.

Researchers are evaluating digital tools to measure speech and fine motor control in people with motor neuron diseases such as amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), and progressive muscular atrophy (PMA). This study compares these digital assessments with the traditional ALS Functional Rating Scale - Revised (ALSFRS-R) to see if they better capture disease severity and daily functional changes. Age-matched healthy individuals will also be included for comparison. During a single study visit, participants will complete speech and handwriting tests on a tablet computer. These tests include a handwriting battery, pattern tracing battery, and speech assessment battery. The study collects data from both patients and healthy controls to explore how well these digital measures reflect the range of functional changes in these motor neuron diseases. Participants will undergo assessments including speaking rate during a standardized passage and a spiral tracing task. Additional evaluations include ALSFRS-R scores, lung function tests (forced vital capacity), upper motor neuron function, and strength testing. The study aims to understand how digital tools compare to standard clinical measures, with all data collected during one visit. The total time commitment is limited to this single session.

Researchers are evaluating the effects of whole-body electrical muscle stimulation (WB-EMS) exercise on neuromuscular and physical function in adults with neuromuscular diseases (NMD) such as amyotrophic lateral sclerosis, spinal muscular atrophy, and myasthenia gravis. People with NMD often face challenges with traditional exercise because of impaired voluntary muscle activation, which can lead to inactivity and worsening health. WB-EMS bypasses these limits by directly stimulating muscle contractions using electrical currents, potentially offering a new way to exercise safely. The intervention uses the Katalyst system, an FDA-cleared device applied off-label, which delivers electrical stimulation to major muscle groups during guided movements. Participants wear a special suit with electrodes connected to an impulse pack controlled via an iPad app. They complete 20-minute supervised exercise sessions 1-2 times per week for 4-8 weeks, following Level 1 strength training videos. Each exercise involves repetitions with stimulation on and off periods, and stimulation levels are adjusted based on participant responses and comfort. Participants will be monitored carefully throughout the study, with evaluations before and after the intervention including neural excitability (using transcranial magnetic stimulation), motor unit behavior (via electromyography and nerve conduction studies), and functional tests like walking, balance, and strength assessments. Patient-reported outcomes on fatigue, pain, and quality of life will also be collected. Safety monitoring is strict, and the study will provide preliminary data on the feasibility and impact of WB-EMS exercise for adults with NMD.

Hereditary Spastic Paraplegia (HSP) is a group of inherited neurological conditions causing progressive weakness and stiffness in the lower limbs, which greatly reduce walking ability and balance. This research aims to evaluate the feasibility and effectiveness of a structured training program designed to improve walking function in adults with HSP by focusing on flexibility, muscle strength, motor control, balance, and aerobic fitness. Participants will take part in 10 to 16 therapy sessions lasting between 60 and 120 minutes each, held once or twice a week according to individual preference. The program includes four key components: flexibility exercises combined with electrical stimulation to reduce muscle tone; resistance training targeting hip and trunk muscles along with balance exercises; motor control-based gait training; and high-intensity interval aerobic training using activities like walking or cycling. After completing the supervised sessions, participants will receive written and video materials to support continued exercise at home. Evaluations will be conducted before the program starts, immediately after it ends (5 to 10 weeks later), and three months after completion. Researchers will assess the feasibility by tracking recruitment, adherence to the sessions, participant retention, safety, and satisfaction. They will also measure changes in walking endurance and speed using standardized walking tests, as well as improvements in muscle strength, balance, and joint mobility.

Researchers are studying adult patients with neurological or metabolic diseases that affect movement, including neuromuscular disorders and obesity, to better understand how these conditions impact motor function over time. This observational study aims to collect detailed real-world data to develop reliable digital measures for future clinical trials. It is conducted at the Centre de Référence Liégeois des Maladies Neuromusculaires in Liège, Belgium, and involves 300 ambulant patients who can walk at least 10 meters without assistance. Participants will wear the Syde® device, a wearable sensor worn on the wrist or ankle, to continuously monitor their motor activity in daily life for up to two years. Clinical assessments, such as timed walking and stair-climbing tests, muscle strength measurements, and motor function evaluations, will be performed every six months. Patients with diseases affecting the neuromuscular junction will be followed for six months. The study also includes patient questionnaires to capture their impressions of change. Throughout the study, researchers will compare continuous data from the Syde® device with traditional clinical tests and questionnaires. They will monitor adherence to device use and evaluate various motor function scales. The main outcome measured every six months is the 95th centile of stride velocity. This approach aims to create meaningful digital endpoints that can enhance future therapeutic research. The total study duration varies by disease type but can last up to two years per participant.