Ataxia

This research focuses on the effects of rehabilitation on balance, in patients with acquired chronic demyelinating neuropathy. Rehabilitation will be performed with or without vision. It is planned to include 40 subjects consulting for walking instability related to sensitivity disorders. This multicenter study will take place in Paris's area. Each participant will benefit from 20 rehabilitation sessions with a Physical Therapist and 3 assessments. Thanks to randomization, patient will be allocated in one of the 2 following groups: * Control group, Patients will benefit from balance rehabilitation with open eyes. * Experimental group, they will perform the same exercises while keeping their eyes closed or their vision will be obstructed by a mask or disturbed by moving luminous dots projected on the environment in darkness.

This international, multi-center, multi-modal and prospective observational study aims to determine the phenotypic spectrum and the natural progression of the RFC1 repeat expansion disease, and to seek and validate digital, imaging, and molecular biomarkers that aid in diagnosis and serve as outcome measures in future clinical trials of this novel, but frequent ataxia with late adult-onset.

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.

Ataxia refers to a group of neurological disorders characterized by impaired coordination and balance due to dysfunction in the cerebellum or its connections. Traditional therapeutic approaches for ataxia have shown limited efficacy, prompting researchers to explore alternative interventions. Non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and intermittent theta burst stimulation (iTBS), have emerged as potential therapeutic options. The aim of this study is to investigate the combined effect of tACS-iTBS on balance functions in ataxia disorders.

In this study, the investigators hypothesize that studying monogenic variants with strong effect associated with severe insulin deficiency of Wolfram syndrome will provide important insights into the more complex type 1 and type 2 diabetes mellitus. Aim 1. Establish and maintain a registry of patients with Wolfram syndrome. An Internet based registry will be employed to enroll participants with the clinical diagnosis of Wolfram syndrome (insulin dependent DM and bilateral OA). Clinical information regarding age of diagnosis and progression of the disease will be collated and analyzed to better define its natural history, along with potential metabolic phenotypes such as glucose intolerance of heterozygous parents and unaffected sibs. If not already completed, blood for WFS1 sequence analysis will be obtained on the participants (parents and sibs also for control purposes) and sent to a CLIA certified lab to define the mutation. This information will benefit patient families and referring physicians by providing a genetic diagnosis and where indicated. The Wolfram Syndrome Registry will foster international collaborations to more efficiently and systematically collect Wolfram syndrome patients and their clinical and experimental data.

Cerebellar ataxias cause progressive impairments in balance, gait coordination, motor timing, and cognitive functions such as attention and executive control (Buckner, 2013; Salmi et al., 2010; Timmann \& Daum, 2007). These symptoms substantially reduce independence and quality of life, and current treatments remain limited. There is an urgent need for safe, low-burden interventions that can support everyday functioning and potentially enhance compensatory neural processes. Transcranial photobiomodulation (tPBM) uses red and near-infrared light (600-1100 nm) to modulate mitochondrial cytochrome-c oxidase, increasing ATP production, reducing oxidative stress, and improving cerebral blood flow (Hamblin, 2016; Salehpour et al., 2019). Several studies show that tPBM can acutely improve cognitive performance and motor control in both healthy adults and clinical groups (Barrett \& Gonzalez-Lima, 2013; Chan et al., 2019; Henderson \& Morries, 2017). A growing neurobiological literature suggests that light can penetrate posterior cortical areas sufficiently to modulate networks involving cerebellar-cortical loops (Jagdeo et al., 2012). Importantly for ataxia, preliminary work shows that tPBM may acutely improve balance stability and gait metrics in older adults and patients with neurological conditions (Moro et al., 2022; Shin et al., 2021). In our own laboratory, we have observed immediate improvements in sway range and cognitive control in older adults after a 24-minute tPBM session applied over midline and posterior scalp regions. These medium to large size effects are consistent with enhanced sensorimotor integration and improved control of attention in distracting environments. Given that individuals with cerebellar ataxia experience both motor incoordination and difficulties in maintaining cognitive stability under distracting conditions, tPBM is a promising non-pharmacological intervention worth preliminary investigation.

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.

The research project is an experimental study with three study visits at the study site at the University Hospital Düsseldorf (UKD) / Heinrich Heine University Düsseldorf (HHU) and a three-week training phase in a parallel design. Patients with movement disorders (ataxia or Parkinson\'s disease) can take part. The training phase includes individually adapted, targeted, video-based coordination and balance training, which should lead to an improvement in gait and balance. Two different training protocols are carried out in parallel for three weeks each: One with 20 minutes of training per day, four days per week; and one with a training duration of 40 minutes per day, only two days per week. All patients initially take part in a one-week familiarization phase without training and are then randomly assigned to one of the two training protocols or the control group without additional training. In both training phases, the total amount of weekly training time is the same, but the frequency and duration of training sessions per week differs. The patients who were assigned to the control group without additional training can complete the training after their third study visit.

Ataxia is a neurological disorder affecting coordination, caused by damage to the cerebellum, brainstem, or related pathways. It can be hereditary (e.g., Friedreich's ataxia) or acquired (e.g., multiple sclerosis, stroke). Though rare, ataxia significantly impacts quality of life and independence. Treatments are limited and mainly focus on multidisciplinary rehabilitation. Accurate assessment is essential, yet current tools like Scale for the Assessment and Rating of Ataxia (SARA) have limitations. This study aims to validate a new scale, named the Ataxia Trunk, Lower And upper extremity Scale (ATLAS), through Rasch analysis, to develop a shorter, reliable version. It will assess internal consistency, construct validity, and inter-rater reliability. For the valitdity part, statistics will be used (1) to see if the different items of the scale are indeed different and complementary to each other, and (2) to compare the results of this scale with other scales already known and valid (SARA, Trunk Impairment Scale (TIS) and Functional Impairment Measurement(FIM)). Secondly, the investigators would like to know whether ATLAS is reliable. In this particular case, the reliability being assessed is inter-rater reliability, i.e. whether all raters give the same score on the items performed by the patient. To carry out such a study, 64 people will be needed to achieve these goals. Each person will complete the 20 items of the ATLAS scale, those of a trunk motor capacity assessment (TIS), and will evaluate his or her functional independence (FIM).

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.

The primary goal of this study is to address the need for targeted therapeutic interventions for impairments that impact walking in related neurodegenerative diseases.

Cerebellar ataxia is a pathology linked to the lesion of the cerebellum or the afferent and/or efferent cerebellar pathways. The aetiology can be an acquired cerebral lesion, following a chemical poisoning or a genetic degenerative lesion (for example : Friedreich's ataxia, spinocerebellar ataxias, etc.). As reported by the latest estimate available, genetic degenerative cerebellar ataxias affect approximately 6,000 patients in France (Orpha.net). Symptoms suffered by ataxic patients are : problems and gait disorders along with difficulties in coordination resulting in ataxia, uncoordinated movements. These symptoms cause a decrease in the quality of life on patients with spinocerebellar ataxia. The symptoms improvement linked to the cerebellar syndrome is based on rehabilitation that can be supplemented by use of technical aids. Current scientific knowledge confirms that intensive rehabilitation by physiotherapy and occupational therapy in patients with degenerative ataxias improves cerebellar symptoms. Nevertheless, the choice rehabilitation technique stay at the appreciation of the therapist. From the observation, the investigators have designed an intensive multidisciplinary rehabilitation program, called PAMPERO, with partner patients member of two genetic degenerative ataxia patient organisations. This 5-weeks program has been used in clinic during 3 years on 28 patients. It appears to be the only one in France. The preliminary results show a positive effect on ataxia symptom. Nevertheless, the duration of the benefice over time and the effect on the quality of life stay unknown. However, the quality of life is mainly affected by the participation restriction due to the risk of falling. The most frequent complaint from partner patient is the diminution of the social interaction resulting of the incapacity to move without risk. The present protocol aimed at evaluating the Rehabilitation Program in collaboration with partner patient on the symptom intensity, activity and quality of life on genetic and degenerative ataxia. This PAMPERO program's effect will be assessed by comparing the difference of Intensity of symptom measured by to Scale for the Assessment and Rating of Ataxia (SARA) at inclusion and 3 months after the end of rehabilitation.