PRIN 2022 Scorrimento - Prot. 2022348C9T - CUP J53C2400305000

Dravet Syndrome (DS) is the most prevalent genetic developmental and epileptic encephalopathy, characterized by drug-resistant seizures, cognitive, behavioral, and motor impairment. DS is caused by loss-of-function variants in SCN1A gene, leading to an excitatory/inhibitory imbalance and consequent predisposition to seizures. Seizures are the first manifestation of the disease, presenting often as febrile status epilepticus before the age of 12 months in infants with a previously normal development. Mild cognitive impairment become evident between ages 2 and 4 years but the learning difficulties become progressively more marked and 80% of adult patients show moderate to severe intellectual disability. Motor features of DS have been less clearly characterized but were repeatedly strongly associated with cognitive performance and quality of life, similarly to what is seen in ageing and neurodegenerative disorders. Moreover, pilot studies have shown a progressive increase of motor disability with ageing, with parkinsonian feature and crouch gait appearing as early as adolescence. Currently available medications for DS have all been licensed for their efficacy against seizure while they have never been tested for their effect on cognitive and motor outcomes. Because of their excitability reducing mechanism of action many antiseizure medication have the potential to significantly affect motor circuits and adverse motor function effects have been observed clinically.

Here, we hypothesize that the lack of a specific motor scale has greatly impaired clinical research on DS by 1) preventing an objective measurement of motor function at different stages of disease; 2) limiting the possibility to detect motor adverse effects of antiseizure medications and 3) impeding reproducibility and sharing of clinical observations across different centers. Therefore, we propose to describe the features, prevalence, and evolution of motor impairment in DS at different disease stages. Subsequently, we will develop a DS-specific motor scale adjusted to be administrable at all ages, as a feasible, validated and reliable new tool. This project will be the first step in the development of the scale. We will assess motor features of patients with DS of different ages, studying both motor function and movement disorders. Motor function will be defined with tasks representative of daily function activities (i.e. manual dexterity in zipping/unzipping, walking speed, etc.) and adapted to be administered at all ages. Ataxia, parkinsonism and hyperkinetic movement disorders will then be separately assessed. We expect this study to have a significant impact on the quality of life of patients by increasing the emphasis on motor function in DS both as a direct measure of ability and independence and as an indirect measure of cognitive and behavioral comorbidities. Importantly, this will help to assess the efficacy of new drugs and novel non-pharmacologic treatments.

Working group:

• Domenica Immacolata Battaglia - Responsabile scientifico UCSC

Partners:

• Università di Pisa

Procedure di selezione:

Procedure chiuse:

• BANDO 679_2025_Battaglia_PRIN 2022 Scorrimento - prot. 679 - Scadenza: 31 luglio 2025 h. 12:00
• Allegato A
• Verbale riunione in presenza