Abstracts

Rationale: The aim of this study was to develop an understanding of the association between time to diagnosis, seizure frequency, management and co-morbidities in a large survey cohort of Dravet syndrome (DS) patients and their caregivers in Europe and test the hypothesis that higher seizure burden in DS is associated with increased co-morbidities and lower quality of life (QoL). Methods: Current seizure frequency, co-morbidities, emergencies, management (pharmacological treatment, therapy for co-morbidities), time to diagnosis and quality of life data from DISCUSS, a pan-European survey of caregivers of patients with DS, were summarised statistically by age groups. Patient characteristics were ranked by current seizure frequency, time to diagnosis, co-morbidities and EQ5D-5L index score and subgroups with the highest and lowest burden were defined. Difference between patient subgroups were assessed in a z test for proportions. Results: The DISCUSS survey cohort consists of 584 caregivers of paediatric (93%) and adult (17%) patients with DS ( < 1 year – 48 years old, mean age 10 years, median 9 years), of which over 90% reside in Europe. Despite broadly following clinical guidance, less than 10% of all patients were seizure free in the previous three months. Half of patients required at least one emergency admission and 46% at least one ambulance call in the past 12 months. Nearly all (99.6%) patients five years or older experienced at least one or more motor, speech, learning or behavioural impairment. More males than females older than two years had a speech impairment (84% vs 76.5%, p=0.035), autism (40% vs 31%, p=0.028) and ADHD (28% vs 14%, p < 0.0001). Patients in the highest seizure frequency subgroup reported more co-morbidities (4.08 +-0.97) than in the lowest (3.41 +-1.28). More patients two years or older in the highest seizure frequency subgroup reported a motor (83% vs 53.8%, p < 0.0001) and speech impairment (89.4% vs 71.4%, p < 0.005). Those in the highest compared to the lowest seizure frequency subgroup more frequently reported one or more emergency admission (56% vs 36%, p < 0.006) or ambulance call (55% vs 30%, p < 0.0001). Less than 3% of patients in the lowest EQ5D-5L index score subgroup, compared to 15% in the highest was seizure free (p < 0002). Patients older than five years using a high number of non-anti-epileptic drug treatments tended to have a higher disease burden: patients with the highest use reported more motor (87% vs 64%, p < 0.0001) and speech impairments (85% vs 69%, p < 0.01) than those not using any non-AED treatments. Conclusions: Families caring for a member with DS must manage multiple impairments in addition to epilepsy symptoms. DS patients with a high current seizure frequency suffer from more co-morbidities, reported more emergency treatments and have a lower QoL compared to patients with a low current seizure frequency. Therefore, more effective anti-epileptic treatment options are still needed for DS patients. Funding: This research was sponsored by Zogenix International Ltd.