Abstracts

Rationale: Little is known about brain structure changes close to the onset of focal epilepsy. The Human Epilepsy Project was designed to address this gap in knowledge and build a profile of epilepsy patients early in the course of their epilepsy that may be used to predict intractability. In this study we present the preliminary results of qualitative and quantitative inspection of MRI acquired early in the course of new onset focal epilepsy. Methods: Whole brain 1 mm isotropic MRI scans were acquired from HEP sites using a standardized MRI protocol. Qualitative analysis consisted of detailed, systematic visual inspection of HEP MRI scans by an expert epileptologist (RK). Quantitative analyses were conducted using Freesurfer v5.3 to determine if there were any differences in: (i) cortical thickness, (ii) brain volume, (iii) gray matter volume, (iv) white matter volume, and (v) ventricle volume. Differences between epilepsy participants and healthy controls, and differences between MRI-negative and MRI-positive cases were examined. Normative quantitative values were derived from a large multisite dataset of 1mm isotropic MRI scans of healthy controls acquired as part of the ABIDE autism study. Results: 27% (n=24) of HEP participants had MRI scans classified as abnormal, 63% (n=56) classified as normal and 10% (n = 9) had MRI abnormalities that were classified as incidental findings. The most common visual findings were bilaterally enlarged or asymmetric ventricles (n = 11). For the quantitative analysis, 59 new onset epilepsy cases (age 32 ± 13.3 years, 40 female) were compared with 216 healthy controls (age 18.9 ± 9.7 years, 35 female). HEP subjects had reduced overall brain volume, GM volume and WM volume (Fig 1, 10 - 12%, p << 0.05); marginally significant increased brain volumes were observed in MRI+ve relative to MRI-ve subjects (4%, p = 0.09). Ventricle volume was significantly increased in MR+ve relative to MR-ve cases, providing quantitative support for the visual findings (64% increase, p = 8.4 × 10-11). No other differences were observed. Age was included as a covariate in all statistical analyses. Conclusions: Approximately one third of the HEP participants imaged to date had qualitatively abnormal MRI. These abnormalities were subtle and the overall impression was of general brain atrophy that was more than expected for the subjects age. Quantitative findings of reduced brain volume & increased ventricle volume support these observations. The HEP study will prospectively track these individuals to determine if they are at greater risk of intractability; if this is the case, MRI-based methods may be a useful marker for intractability. Funding: 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, Finding A Cure for Epilepsy and Seizures, Pfizer, Lundbeck, The Andrews Foundation, Friends of Faces and others).