Rationale:
Dravet syndrome (DS) is a severe and progressive developmental and epileptic encephalopathy that begins in the first year of life and is characterized by high seizure frequency and severity, intellectual disability, and a high risk of sudden unexpected death in epilepsy. There remains a significant need for therapy to reduce seizure frequency and improve non-seizure comorbidities in DS patients. Limited prospective long-term data exist regarding the course of non-seizure comorbidities in DS patients. This observational study aims to evaluate the course of neurodevelopmental status, adaptive functioning, gait performance, quality of life, seizure frequency, and sleep in DS patients over 2 years. Baseline data obtained in this study will be presented.
Method:
This ongoing multicenter, longitudinal, prospective study includes patients aged 2-18 years with genetically confirmed DS whose seizures were not controlled by their current antiepileptic drug (AED) regimen. Patients are assessed at 6 study visits up to 24 months. Primary endpoints assess neurodevelopment and change from baseline to 24 months according to the following scales: VABS-3 and BSID-III or WPPSI-IV. Other secondary and exploratory endpoints will look at the frequency of convulsive seizures, change in clinical status, change in executive function, total sleep time, seizure frequency, and ambulation and gait, all of which will be reported.
Results:
At the time of this analysis, 14 of 36 patients (mean age at baseline 11.1 years, 64% females, and 86% white) have been enrolled. The top 5 concomitant medications used for seizure treatment at the time of screening were clobazam, cannabidiol, levetiracetam, stiripentol, and valproic acid/valproate, and patients were using 2-10 AEDs at time of enrollment. At baseline, 10 patients completed the BSID-III and 11 patients the WPPSI-IV. BSID-III age equivalent mean scores for cognitive (22.44), language (expressive 15.71, receptive 18.75), and motor (fine 23.00, gross 20.29) showed severe developmental delays. WPPSI-IV scores demonstrated that the majority of pre-school-aged patients had average cognitive ability, but the school-aged patients were significantly impaired. VABS-3 age equivalent scores varied but revealed significant delays from age equivalent peer groups in adaptive functioning (Fig 1).
Conclusion:
The patients enrolled to date in this observational study are representative of patients with DS. Importantly, the data collected indicate that the selected cognition measures are valid and appropriate for use in patients with DS, as all patients were able to complete either the BSID-III or WPPSI-IV. There is evidence of heterogeneity and large variability between patients, and substantially decreased abilities in comparison to children at the same chronological age level. The data collected in this long-term prospective study will provide valuable insights on the course of non-seizure comorbidities in people with DS.
Funding:
:Sponsored by Stoke Therapeutics
FIGURES
Figure 1