Clinical and genetic features of acute deterioration with resulting neurological regression in children with Dravet Syndrome

Objectives: To investigate the clinical and genetic features of acute deterioration with resulting neurological regression in children with Dravet syndrome.

Methods: Case-notes of children with Dravet syndrome with a history of acute deterioration leading to neurological regression were gathered from 2 tertiary centres in London. Clinical features prior to, during and after their acute deterioration were reviewed, including demographics, baseline anti-seizure medication, seizure frequency, seizure duration, rescue medication, neuroimaging and EEG findings. In addition, analysis of each variant within SCN1A using CLINVAR and SCN portal was undertaken including, where applicable, a review of previously reported identical variants. Data was analysed, alongside literature review, to identify ‘risk factors’ predictive of acute deteriorations and resulting neurological regression.

Results: 18 children were identified. 17/18 had an episode of status epilepticus; 2/17 had a cardiac arrest during status epilepticus and survived whilst 4/16 had a cardiac arrest and died. One patient had sepsis without status epilepticus leading to sustained regression. All 18 patients had SCN1A variants located in functional locations/domains within Nav1.1. On initial analysis, no variables were predictive of an acute decompensation and persisting neurological regression.

Conclusion: This case series demonstrated no patient characteristics, including SCN1A variants, associated with episodes of acute deterioration and neurologic regression to further inform the management or prognosis for children with Dravet Syndrome. Further analysis is ongoing including comparison to children with Dravet syndrome without acute neurological deterioration.