Abstracts

Rationale: The Human Epilepsy Study (HEP) is a prospective observational study that aims to identify markers of treatment response in newly treated focal epilepsy. We evaluated seizure frequency, imaging, EEG and demographic characteristics in participants with >=80% adherence to an electronic seizure diary. We sought to compare those with debilitating seizures - focal unaware - to participants with no seizures after enrollment. Methods: We recruited participants from 33 sites in the US, Australia, Austria and Finland. Inclusion criteria included: focal epilepsy, age 12-60 years, within 4 months of treatment initiation, and no major progressive neurological condition. 450 participants were enrolled. All received an electronic diary to track seizure frequency, and seizure types were adjudicated by a panel of epileptologists. We selected participants enrolled for >=6 months with >=80% seizure diary compliance. We excluded all focal aware seizures or other event types for which adjudication was inconclusive. We did not include AED usage in this analysis. We then compared participants with >= 1 focal unaware seizure recorded in the diary to those with no seizures recorded after enrollment. We also analyzed adjudicated EEG and MRI results, derived from a mix of clinical and research studies. Results: Sixty-two participants recorded no seizures while 68 participants recorded ≥1 focal unaware seizure. Mean duration of enrollment was 35.2 months (range 17-73) for the no-seizure (NS) group, and 35.3 (9.9-66.8) for the focal unaware seizure (FUS) group. 48.4% of NS were women, while the FUS group was 68.7% female. More participants in the NS group had a postgraduate degree (23.8% vs 8.6%).We evaluated 10,425 seizure diary entries. Participants in the FUS group averaged 1.5 seizures per month (all types; median 0.3), of which nearly half were FUS (mean 0.7; median 0.2). Participants in this group averaged at least one FUS in 20.7% of the months enrolled; this increased to 29.1% if all seizure types were included.  A greater percentage of the NS group had a normal MRI (63.3%) or normal EEG (51.6%) than the FUS group (54.5% and 38.5%, respectively). 45.5% of FUS EEGs had epileptiform discharges recorded, compared with only 23.3% of those in the NS group.  Conclusions: This is the first comprehensive report of seizure frequencies from HEP, the largest prospective study of newly treated focal epilepsy to date. A nearly equal proportion of diary-adherent participants had no seizures post-enrollment as had >=1 focal unaware seizures. This is not equivalent to treatment resistance, as there was variable exposure to AEDs at enrollment. The FUS group may therefore include participants who later became seizure-free on an AED. Those with FUS had seizures roughly once for every five months enrolled, were more likely to be women, less likely to have a postgraduate degree, and were more likely to have an abnormal EEG and MRI. Future directions include analyses of AED usage, psychiatric comorbidities, and blood samples from these cohorts, as well as analyses of less-adherent diary users. Funding: The HEP study is supported by the Epilepsy Study Consortium (ESCI), a non-profit organization dedicated to accelerating the development of new therapies in epilepsy to improve patient care. The funding provided to ESCI to support HEP comes from industry, philanthropy and foundations (UCB Pharma, Eisai, Pfizer, Lundbeck, Sunovion, The Andrews Foundation, The Vogelstein Foundation, Finding A Cure for Epilepsy and Seizures (FACES), Friends of Faces and others).