Friedreich's Ataxia, Motor Disorders
Conditions
Keywords
Functional Connectivity, HD-EEG, FRDA, Connectome, Cognitive Functioning, Neurodegenerative Disease, Cerebellar Disorders, Neurophysiological Biomarkers, Friedreich Ataxia
Brief summary
Prospective, exploratory, multicenter pilot study investigating the structural and functional connectome in patients with Friedreich's Ataxia (FRDA) using high-density electroencephalogram (HD-EEG). The aim is to identify neurophysiological biomarkers and analyze the relationship between cortical connectivity, cognitive functioning, and clinical severity, particularly in response to rehabilitation treatment.
Detailed description
Friedreich's Ataxia (FRDA) is a progressive neurodegenerative disease caused by mutations in the FXN gene, resulting in a reduction in the mitochondrial protein frataxin and a dysfunction in iron homeostasis. In addition to motor and sensory impairments, FRDA also results in cognitive and emotional deficits. Pathophysiologically, it is associated with cerebellar degeneration and alterations in cerebello-cortical networks. The present study proposes a novel HD-EEG-based approach to analyze brain activity at resting-state and during the performance of a motor task (task-based) in subjects with FRDA. Thirty patients with confirmed genetic diagnosis, age between 8 and 60 years, and SARA score \<30 will be recruited. EEG recordings will be performed in resting condition and during an upper limb motor task. In addition to neurophysiological measures, each participant will undergo a comprehensive neuropsychological evaluation, including memory, attention, language, visuospatial skills, praxis, executive functions, emotional and personality aspects. Connectivity data will be correlated with cognitive profiles and scores on the SARA and mFARS clinical scales.
Interventions
DEVICEHD-EEG recordings, combined with cognitive and motor assessment
Participants will undergo high-density EEG (HD-EEG) recordings under two conditions: at rest and while performing an upper limb motor task. The data obtained will be used to reconstruct source cortical activity and derive patterns of functional connectivity, using advanced neurophysiological analysis techniques, including the Avalanche Transition Matrix (ATM). In addition, patients will complete a neuropsychological assessment and participate in an intensive multidisciplinary rehabilitation program lasting 3 to 4 weeks, depending on age. The intervention aims to assess changes in the functional organization of the brain before and after treatment, as well as one year later, in order to explore potential biomarkers of disease progression.
Sponsors
IRCCS Eugenio Medea
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* age between 8 and 60 years; * genetic diagnosis of FRDA: presence of guanine-adenine trinucleotide (GAA) expansion in the two alleles of the fratassin gene, GAA1 and GAA2; * score on the Scale for the Assessment and Rating of Ataxia (SARA) \< 30; * ability to take part in a neuropsychological assessment in Italian.
Exclusion criteria
* age different from the range 8-60 years; * diagnosis of acquired ataxia or other genetic ataxias; * SARA scale score ≥ 30; * inability to take part in an Italian-language neuropsychological assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Connectivity profile derived from HD-EEG in subjects with FRDA. | From enrollment to the end of treatment at 3 to 4 weeks and after 1 year of follow-up | Characterization of alterations in the connectome derived from the HD-EEG of subjects with FRDA compared with matched controls; |
| Functional activity derived from HD-EEG in subjects with FRDA. | From enrollment to the end of treatment at 3 to 4 weeks and after 1 year of follow-up | Evaluation of functional connectivity as a biomarker in the evolution of FRDA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between functional connectivity/activity and quantitative parameters derived from neuropsychological scales. Correlation between functional connectivity/activity and quantitative parameters derived from motor scales (SARA and mFARS). | From enrollment to the end of treatment at 3 to 4 weeks and after 1 year of follow-up | 1. acquisition of new knowledge about the neuronal basis of impaired neurocognitive functioning in FRDA; 2. evaluation of possible correlations with disease severity scales pre- and post-rehabilitation treatment. |
Countries
Italy
Contacts
Primary ContactGabriella Paparella, Medical Degree
Outcome results
None listed