Abstracts

Rationale: Dravet syndrome (DS) is a rare and severe infantile onset developmental epileptic encephalopathy characterised by intractable multiple seizure type including prolonged febrile seizures and progressive cognitive and motor impairment. It is associated with mutations in SCN1A in > 80%, MRI studies are normal in the majority of patients and there is no evidence of a histopathological hallmark. However, mesial temporal sclerosis (MTS) has been described even though results regarding the prevalence differ significantly between the studies. While it has been now demonstrated that prolonged febrile seizures can result in hippocampal injury, it is still unclear why not a greater proportion of DS patients show hippocampal abnormalities. It is also unknown whether the hippocampal changes are due to the prolonged febrile seizures or if the sodium channel dysfunction itself plays a role. Methods: We reviewed retrospectively a cohort of patients with a clinical pattern of DS and proven SCN1A mutation and compared our findings with previous reports. Results: We identified 31 children (16 females and 15 males) with a median age of 12.5 years (min 17 months, max 19.9 years). Seizure onset was in 94% (29/31) before 12 months of age; one patient experienced the first seizure at 13m and another at 18m of age. Prolonged febrile seizures were present in 24/31 (77%) and a similar proportion of patients, 22/31 (71%), experienced prolonged afebrile seizures. Early development was unremarkable in the majority of the patients (24/31), 6 had a borderline-mild developmental delay and 1 patient with concomitant diagnosis of malonic aciduria had a global developmental delay prior onset of epilepsy disorder. All but two patients presented then with cognitive impairment of various degree. 29/31 underwent a brain MRI study at a median age of 19 months (min 4-max 130months). Only one patient presented with definite unilateral MTS, diagnosed at the age of 11 years and confirmed by subsequent repeat MRI. Another patient showed a volume reduction of the body of the left hippocampus without signal abnormality at the age of 35 months and had normal follow-up MRI 2 years later (57months). Conclusions: Our clinical data provide evidence that MTS is indeed not frequent in children with DS despite of 77% presenting with prolonged febrile seizures. A protective role of the sodium channel mutation modulating the excitotoxicity-associated increase in NMDA-induced calcium influx during prolonged febrile seizures has been hypothesised but has yet to be confirmed. However, MRI control at a later stage might reveal hippocampal damage as shown by Siegler et al even though not confirmed by a more recent study in a cohort of 22 adult patients with DS. More data are required to confirm a difference regarding incidence of MTS between SCN1A positive and negative patients and prospective studies to determine if MTS appears in adulthood. Funding: None