Multicentre prospective study in patients affected by Dravet Syndrome.

Dravet syndrome (DS) is a rare and severe form of epilepsy, associated with mutations of SCN1A gene, encoding for the sodium channel voltage-dependent Nav.1.1. Epilepsy appears in the first year of life in an otherwise healthy infant. The disease is progressive and during its course neurological signs change, comorbidities appear and cognitive deficits become highly disabling. Nowadays, only few prospective longitudinal studies have been reported. Aims of this study are to perform a multicentre prospective evaluation of a group of Italian Dravet patients, carrying a SCN1A mutation, followed from the first year of life, in order to: Describe the epileptological onset and evolution, Describe neurological features, Identify the onset of a neurodevelopmental impairment, Evaluate the presence of associated behavioural disorders, Perform a correlation analysis between genetic determinants and cognitive evolution, Perform a correlation analysis between the cognitive evolution and epileptological variables. Aims of the second part of the study are to perform a prospective evaluation of a sample of Dravet patients and a control group followed in a tertiary neurological centre, followed from seizure onset in order to: Compare clinical and electrophysiological features during the first years of life, Define etiologic determinants in the control group to reach an early diagnosis and to give targeted treatment. In the first part of the study 17 Dravet patients, all carrying a mutation in SCN1A, were enrolled. The analysis of the data collected, allowed us to highlight the following remarks: the onset of febrile and/or prolonged seizures within the 6th month in a previously healthy child represents one of the typical features of Dravet Syndrome: in our series the first seizure occurred within the sixth month in 88% of the infants. Most of patients of the sample (75%), presented one or more convulsive status within the 12th month of age. Interictal myoclonus represents a common neurological sign: in our sample this already appeared at the 12th month. The association of these early findings, in an otherwise healthy patient, especially when associated with a normal EEG, can be considered a useful tool to recognize early the disease. We performed neuropsychological assessments, from the first months of the disease in order to follow its evolution. A progressive slowing appeared between the 12th and the 18th month in most of the patients. The correlation analysis between genetic determinants and cognitive evolution did not provide any evidence for a correlation between the type of mutation and the cognitive outcome. The correlation between the epilepsy course and the cognitive outcome highlighted that an early onset of seizures represents a negative prognostic factor for cognitive evolution. It’s conceivable that epileptic phenotype may play a role in determining the final cognitive outcome, but, it does not seem that a more early and targeted treatment can really modify the natural history of the disease. So other genetic and environmental factors need to be considered. In the second part of the study we performed a prospective evaluation of a sample of Dravet patients with a control group. These observations confirm what we stated above: The early onset of the seizures may lead the clinical diagnosis towards Dravet Syndrome, in our control group, only 2 patients out of 9 experienced their first seizures within the 6th month of age. The occurrence of the seizures and the status epilepticus during the first years of life can be observed in Dravet Syndrome and in other forms of genetic epilepsy, but the persistence of polymorphic, drugs-resistant seizures is more common in Dravet Syndrome. A steep decrease in the General Quotient is usually observed in Dravet Syndrome, whereas patients with other forms of genetic epilepsy show a milder decrease despite often presenting a lower GQ from the beginning.