Bodãƒâ¸, Norway

Flexibility, Resistance, Aerobic, Movement Execution Training in Adults with Hereditary Spastic Paraplegia

INTRODUCTION: Hereditary Spastic Paraplegia (HSP) is a heterogeneous group of inherited neurological disorders characterized by progressive weakness and spasticity in the lower limbs, which significantly impairs walking abilities (endurance and speed). Despite several specific interventions for particular deficits already having been studied, there is currently a lack of comprehensive and structured neurorehabilitation programs designed to improve walking function in these patients. Therefore, this protocol aims to explore the feasibility and effectiveness of a composite training approach focused on improving flexibility, muscle strength, motor control, balance, and aerobic capacity. STUDY OBJECTIVES: Primary endpoint: Feasibility of the study, assessed by the following: Sufficient recruitment rate, with 20 patients enrolled within 24 months from the study's initiation. Adequate adherence to the treatment plan, defined by the completion of at least 75% of the planned treatment sessions, with a minimum of 10 treatment sessions. Sufficient patient retention, defined as at least 75% of enrolled patients completing the study with adequate treatment adherence. Absence of serious adverse events related to patient participation in the study. Patient satisfaction with the healthcare received during the study. Secondary endpoint: Therapeutic efficacy of the study, assessed by: Improvement in walking endurance (6-Minute Walk Test). Improvement in walking speed (10-Meter Walk Test). Exploratory objectives: Improvement in overall functional condition (Spastic Paraplegia Rating Scale and the Hereditary Spastic Paraplegia - Self Notion and Perception Questionnaire). Improvement in passive joint range of motion in the lower limbs (goniometer). Improvement in lower limb muscle strength (5 Times Sit-to-Stand Test). Improvement in standing balance (Functional Reach Test and stabilometric platform). STUDY DESIGN: Open-label, non-randomized, uncontrolled interventional study. STUDY POPULATION: Hereditary Spastic Paraplegia patients SAMPLE SIZE: 20 patients ELIGIBILITY: Inclusion criteria: Adults diagnosed with Hereditary Spastic Paraplegia. Presence of any functional deficit in the lower limbs affecting walking, such as muscle weakness, hypertonia, or balance issues. Ability to walk independently, without physical assistance from another person, defined by a Functional Ambulation Category score of 3 or higher. Ability to understand simple instructions, comprehend the purpose of the study, willingness to participate, commitment to at least 10 treatment sessions, and suitability for signing the informed consent. Exclusion criteria: Use of botulinum toxin or surgery to treat lower limb hypertonia within six months prior to study enrollment. Contraindications for moderate physical activity, including stretching exercises, muscle strengthening, and aerobic training. Withdrawal Criteria: Voluntary withdrawal by the patient. Occurrence of adverse events or health issues that prevent continuation of the treatment plan. Patient Replacement: Recruitment will continue until 20 subjects are enrolled. Any patients who withdraw from the study will not be replaced. METHODS: Twenty adults diagnosed with HSP will participate in 10 to 16 therapist-guided sessions, each lasting 60 or 120 minutes, occurring once or twice a week depending on individual choice and capabilities. At the conclusion of the study, participants will receive an information package (manual and video tutorials) to support long-term home exercise. Evaluations will take place at three time points: before the intervention (T0), immediately after the intervention (T1), and three months post-intervention (T2). The primary objectives will focus on assessing the study's feasibility (recruitment, retention, adherence, absence of adverse events, and patient satisfaction). Secondary outcomes will evaluate improvements in walking ability and specific contributing factors, such as reduced spasticity, increased muscle strength, and improved balance. INTERVENTION: FRAME training is composed of four key components: Component 1: Flexibility. To decrease muscle tone and enhance mobility, the therapist will apply a combination of stretching exercises and electrical stimulation, targeting areas such as the triceps surae, adductors, rectus femoris, and hamstrings. Electrical stimulation will utilize biphasic, high-frequency sensory stimulation (100 Hertz, pulse width 200 µs, and intensity just below the motor threshold) for a duration of 30 minutes, combined with stretching activities. Component 2: Resistance Training (and Balance). The resistance training will focus on strengthening muscles typically weakened in individuals with Hereditary Spastic Paraplegia (HSP), especially the proximal muscles of the hip and trunk. To promote muscle engagement and improve balance and coordination, core stability and resistance exercises will be performed under conditions of mild instability. These exercises will be carried out in sitting or standing positions, rather than lying down, to optimize muscle activation. Component 3: Movement Execution (and Balance). Gait training will be based on motor learning principles such as repetitive, task-oriented practice, variable practice, and graded practice. Graded practice involves breaking down a complex movement into simpler segments, practicing each segment until proficiency is achieved, and then progressively combining them into more complex sequences. Patients will be challenged with standing balance exercises while working on specific gait impairments. Gait training will involve varying walking patterns, including fast, slow, sidewalk walking, walking backward, and stair climbing. Component 4: Aerobic Training via High-Intensity Interval Training (HIIT). HIIT consists of brief, intense aerobic efforts using large muscle groups, followed by rest periods of equal length. HIIT has been found to produce better cardiovascular results with a lower perceived level of effort compared to moderate-intensity aerobic exercise. In this protocol, patients will perform 30-second high-intensity intervals followed by 30 seconds of passive rest, repeated 10 times in two sets. Each session will begin with a 5-minute warm-up, include a 5-minute rest between sets, and conclude with a 5-minute cool-down. Patients will participate in the modality most suitable for consistent training, such as walking, running, cycling, or squatting. RELEVANCE: This protocol is significant for providing clinicians with valuable insights into the feasibility and potential effectiveness of a comprehensive, clinically-oriented program designed to improve walking ability in adults with Hereditary Spastic Paraplegia. It also aims to inform future translational research studies in the field.

Efficacy of Stabilometric Platform to Improve Standing Balance in Patients With Friedreich's Ataxia

In recent years, there has been increasing interest in the scientific literature on degenerative diseases such as ataxic syndromes. Friedreich's Ataxia is one of the most common forms of hereditary ataxia. It is defined as a multisystemic neurodegenerative disorder with an autosomal recessive inheritance pattern, presenting both neurological and non-neurological clinical manifestations. The disease results from a mutation in the X25 gene on chromosome 9, characterized by an excessive repetition of the GAA trinucleotide, which leads to a reduction and malfunction of frataxin. Friedreich's Ataxia typically manifests in the first or second decade of life, with a significant functional impact and progressive disability. Often, initial symptoms are characterized by severe balance and coordination impairments, which not only affect functional independence but also patients' quality of life. Currently, therapeutic options are very limited. Omaveloxolone is the first and only drug approved in 2023 by the Food and Drug Administration and The European Medicines Agency for adults and adolescents aged ≥16 with Friedreich's Ataxia. It has been shown to improve the score on the Modified Friedreich's Ataxia Rating Scale after chronic treatment. Rehabilitation is defined by the World Health Organization as a set of interventions designed to reduce disability and optimize functioning in individuals interacting with their environment. Current literature suggests that rehabilitation plays a central role in the treatment of Friedreich's Ataxia. Impairments and limitations associated with Friedreich's Ataxia can be addressed through rehabilitative procedures that, although they do not affect disease progression, may significantly improve the patient's functionality. Several studies indicated that the use of technological aids in neurorehabilitation leads to improvements in various conditions. Technological aids offer several advantages over traditional rehabilitation by significantly contributing to motor learning and brain plasticity, both of which are key to improving motor recovery. These aids can be easily tailored to the specific needs of each patient. Technology-based rehabilitation platforms can adjust the difficulty level and type of exercises according to the patient's progress, ensuring a personalized approach. The use of technologies such as virtual reality and interactive games makes rehabilitation more engaging and enjoyable. This increases patients' motivation to actively participate in rehabilitation sessions, improving adherence to treatment. Technologies can provide real-time feedback on patient performance, enabling immediate adjustments and enhancing motor learning. This type of feedback is crucial for improving body awareness and movement precision. Additionally, technologies can integrate visual, auditory, and tactile stimuli, which can enhance learning and brain plasticity. One technological aid used in rehabilitation is the stabilometric platform. This consists of a platform equipped with sensors that record the oscillations of the body's center of gravity while the patient stands on it. These data can be used to analyze postural stability, detect balance problems, and monitor progress in rehabilitation programs. It is often used in fields such as physiotherapy, sports, and biomechanical research. In recent years, it has also been used as a rehabilitative tool to improve balance, coordination, and proprioception, including in the neurological field. Integrating the stabilometric platform into rehabilitation programs offers a more comprehensive and targeted approach to addressing balance and postural stability issues. Several studies have compared conventional rehabilitation with combined treatments involving the stabilometric platform. Results indicate that conventional balance training can improve balance function in patients, but when combined with visual feedback balance training, the improvements are more significant. In the literature, the use of the stabilometric platform combined with traditional physiotherapy has shown considerable effectiveness in resolving balance deficits in patients with various neurological conditions, though this has not been demonstrated in . In the literature on Friedreich's Ataxia, several studies have used this tool for assessment purposes. Balance parameters obtained using the stabilometric platform have shown a significant increase over time in patients with Friedreich's Ataxia, indicating impaired postural stability and balance while standing. These measures are significantly correlated with performance scores on the Friedreich's Ataxia Rating Scale, particularly with the Friedreich's Ataxia Rating Scale subscale on Upright Stability. However, there are no specific studies regarding the application of this device as a rehabilitative tool in Friedreich's Ataxia. According to the existing literature, the investigators propose an open-label, monocentric, randomized pilot study to compare the effectiveness of a conventional rehabilitation program combined with training on the stabilometric platform (Group A) versus conventional rehabilitation alone (Group B) in improving balance reactions specifically in patients with mild to moderate Friedreich's Ataxia. The investigators will use the Prokin 252 system on the Tecnobody stabilometric platform. Enrolled patients will be randomly assigned to one of the two treatment groups for four weeks. Three assessments will be conducted for each patient: one before treatment (T0), one at the end of treatment (T1), and a follow-up assessment 90 days after T1 via telemedicine (T2). At T0 and T1, assessments will include tests and scales that measure the patient's overall functioning, commonly used in clinical practice, such as the Modified Friedreich's Ataxia Rating Scale, Scale for Assessment and Rating of Ataxia, 6-Minute Walk Test, Timed Up and Go, Berg Balance Scale, and Functional Reach Test. Additionally, using the stabilometric platform, patients will perform static stability and limits of stability tests while standing. At T2, patients will be reassessed via telemedicine with only the Modified Friedreich's Ataxia Rating Scale administered and Scale for Assessment and Rating of Ataxia. Changes in scores obtained on scales and on stabilometric platform parameters will serve as the evaluation criteria for the potential effectiveness of the treatment, also compared to the outcomes of standard physiotherapy treatment.

Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders

The investigators will perform a registry-based standardized prospective Natural History Study (NHS) in HSPs and related disorders. Participants will be seen annually. At study visits a standardized clinical examination will be performed including application of clinical rating scales (selection of rating scales may vary depending on the individual phenotype and specific genotype); data will be entered into a clinical database (HSP Registry; https://www.hsp-registry.net). At all study visits, patients will be asked to donate biosamples; biomaterial collection is optional and participants can elect to participate in sampling of blood, urine, CSF, and/or a skin biopsy. Optionally, additional examinations may be performed including imaging, quantitative movement analysis, neuropsychological examinations, analysis of patient or observer reported outcomes and OMICS analysis to characterize molecular biomarkers. In participants without a genetic diagnosis, next generation sequencing may be performed.

Rivaroxaban for the Treatment of Symptomatic Isolated Distal Deep Vein Thrombosis