Abstracts

Rationale: SMEI,or Dravet syndrome,is an epileptic encephalopathy, frequently resulting from a de novo mutation of the SCN1A gene. The seizures onset is in the first year of life, but diagnosis is often delay at the age of 2-3 years when the electroclinical picture is enriched by cognitive deterioration, myoclonus and ataxia. Aims of our study were a)to identify the early electroclinical manifestations of SMEI that can prompt an early diagnosis, genetic investigation and targeted treatment b)to evaluate the cognitive outcome in relation with the epileptic phenotype. Methods: The case series includes 22 patients (present age, 11 months-27 years) that met the diagnostic criteria of SMEI, according to the ILAE classification. The patients have been followed at our Institute for a mean period of 6 years (range 2 months-18 years). The follow-up included clinical and EEG examinations, as well as standardized cognitive evaluation. Alpha-subunit type A of voltage-gated sodium channel (SCN1A) mutational screening was performed by DHPLC and multiplex ligation probe amplification (MLPA)Results: A positive family history for epilepsy and/or febrile convulsions was reported in 55% of cases. All the infants were normal before the onset of epilepsy. The mean age at the first seizure was 5.4 months (range 3-11 months). In 9 cases, the first symptom was an isolated focal, hemigeneralized or generalized clonic seizures, that occurred during a febrile illness in 4. In the 12 remaining patients the onset was marked by epileptic status, in the course of hyperthermia in 9. The first EEG was normal in all cases. During the second year of life, the disease course was characterized by recurrence of polymorphic, difficult to treat, seizures, that, in most cases were triggered by fever, bathing with hot water, and intermittent lights. At this age epileptic activity and/or EEG photosensitivity also appeared. From the second year of life a slowing or arrest of psychomotor development was evident in 20 patients, followed in 15 cases by the appearance of behaviour disorders. Cognitive skills and behaviour disorders usually worsened in the periods of higher seizure frequency. During the follow-up the neurologic examination revealed deficits in 14 patients, characterized by ataxia, pyramidal symptoms, and myoclonus. The genetic analysis detected mutations of SCN1A gene in 16 cases, including a truncate mutation in 11 cases and a missense mutation in 5. In 3 patients genetic analysis is still ongoing. Conclusions: A tentative diagnosis of SMEI may be proposed by the end of the first year of life in an infant presenting with febrile status, or recurrent focal seizures and normal EEG, particularly in presence of a positive family history. A definite diagnosis can be established during the second year based on the peculiar seizure-favouring factors, EEG photosensitivity and psychomotor slowing. The temporal correlation between the high frequency of seizures and the onset of neurologic and cognitive impairment support the role of epileptic activity in the final outcome.