Badanie markerów choroby mózgu, plastyczności synaps i zapalenia w zespole Dravet

Dravet syndrome (DS) is a developmental and epileptic encephalopathy, usually caused by de novo pathogenic SCN1A variants, characterized by early-onset prolonged febrile seizures, subsequent drug-resistant polymorphic epilepsy, developmental impairment, and, in some patients, progressive motor, cognitive and behavioral decline. Despite the expanding therapeutic landscape, objective biomarkers for disease stratification, monitoring and treatment response are lacking. Blood-based markers of neurodegeneration, synaptic plasticity and neuroinflammation are promising candidates because they are minimally invasive and may capture biological processes involved in disease progression. TEMBO-DS is a prospective multicenter observational pilot study enrolling 60 individuals with DS and 30 age- and sex-matched healthy controls. DS participants will carry pathogenic or likely pathogenic SCN1A variants and fulfill ILAE clinical criteria, with no age limits. Individuals with epileptic spasms, SCN1A gain-of-function encephalopathy, structural causes of epilepsy, or systemic, oncological, autoimmune or neurodegenerative conditions potentially affecting biomarker levels will be excluded. At baseline, demographic and clinical variables will be collected, including age at seizure onset, seizure type and frequency, status epilepticus, SCN1A variant type, cognitive, motor, behavioral and sleep profiles, comorbidities and ongoing treatments. Blood samples obtained during routine clinical sampling will be analyzed for biomarkers of neurodegeneration and glial injury (NfL, GFAP, tau-related markers), synaptic plasticity (BDNF) and neuroinflammation. In a subgroup of DS participants, clinical assessment and blood sampling will be repeated after approximately 12 months. The study will assess whether biomarker levels differ between DS and controls and whether they correlate with clinically relevant measures of disease severity and longitudinal change. Particular emphasis will be placed on the relationship between NfL and Vineland adaptive functioning, including their changes over 12 months and the effect of treatment modifications. Group comparisons, correlation analyses and longitudinal mixed-effects models will be used, with adjustment for relevant covariates and multiple testing. The study is expected to identify one or more blood-based biomarkers, or biomarker combinations, associated with DS, disease severity and clinical evolution. These findings may provide objective measures for future natural-history studies and therapeutic trials, including the assessment of non-seizure outcomes.