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.

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.

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

Anonymized individual participant data will be shared with other researchers upon reasonable request

Start date: January 2028 End date: January 2038

Any researchers accredited by non-profit clinical and research center