SUDEP

…risk of sudden death, known as SUDEP. The DEPDC5 gene is a common factor in familial focal epilepsy, with or without cortical malformations, and its pathogenic variants increase the susceptibility to SUDEP. This study aims to gain a mechanistic understanding of DEPDC5-related epilepsy and SUDEP, identify biomarkers for high-risk patients, and develop preventive interventions.Methods involved the targeted deletion of Depdc5 in nucleus tractus solitarius (NTS) neurons in the mouse brainstem, followed by the administra

…sudden unexpected death in epilepsy (SUDEP). The disease is caused by haploinsufficiency of SCN1A gene, encoding the alpha subunit of the voltage-gated sodium channel Nav1.1. While DS onset is triggered by interneuron (IN) hypoexcitability, alterations in glutamatergic neurons contribute to its progression. Current gene therapy strategies aim to boost SCN1A gene expression in INs, prompting this study to investigate whether targeting them alone at various disease stages is suffici

Sudden unexpected death in epilepsy (SUDEP) is a dramatic outcome for epileptic patients, with a prevalence of 1 per 1000. Stiripentol (STP, Diacomit©) is an antiseizure medication indicated for Dravet syndrome, a rare developmental and epileptic encephalopathy with high mortality rate (15 per 1000), in which SUDEP accounts for about 2/3. Here, we evaluate the effects of STP on seizures and death using audiogenic seizure in a preclinical model of SUDEP.In the DBA/2 SUDEP model, audiogenic seizures were induced, and different concentrations of STP were tested at various timings between administ

…Sudden unexplained death in epilepsy (SUDEP) is strongly associated with sleep. The biological mechanisms underlying this relationship between seizures and sleep are poorly understood,

The long-term goal of our research is to understand the mechanisms of SUDEP, defined as Sudden, Unexpected, witnessed or unwitnessed, nontraumatic and non-drowning Death in patients with EPilepsy, excluding cases of documented status epilepticus. The majority of SUDEP patients die during sleep. SUDEP is the most devastating consequence of epilepsy, yet little is understood about its causes and no biomarkers exist to identify at risk patients. While SUDEP accounts for 7.5-20% of all epilepsy deaths, SUDEP risk in the genetic epilepsies varies with affected genes. Patients with ion channel gene

Dravet syndrome is a severe epileptic encephalopathy that begins during the first year of life and leads to severe cognitive and social interaction deficits. It is mostly caused by heterozygous loss-of-function mutations in the SCN1A gene, which encodes for the alpha-subunit of the voltage-gated sodium channel (Nav1.1) and is responsible mainly of GABAergic interneuron excitability. While different therapies based on the upregulation of the healthy allele of the gene are being developed, the dynamics of reversibility of the pathology are still unclear. In fact, whether and to which extent the

Dravet syndrome (DS) is a neurodevelopmental disorder caused by heterozygous loss-of-function of the gene SCN1A encoding the voltage-gated sodium channel subunit Nav1.1, and is defined by treatment-resistant epilepsy, intellectual impairment, and sudden death. However, disease mechanisms remain unclear, as previously-identified deficiency in action potential generation of Nav1.1-expressing parvalbumin-positive fast-spiking GABAergic interneurons (PV-INs) in DS (Scn1a+/-) mice normalizes during development. We used a novel approach that facilitated the assessment of PV-IN function at both early