PhD Candidate Geisel School of Medicine at Dartmouth
Rationale: Certain subject-specific factors were shown to influence interictal epileptiform discharge (IED) rates. However, the relative importance of these factors remains unknown, as most previous studies assessed specific factors in isolation. In this study, we aim to systematically evaluate the influence that subject-specific factors have on IED rates in persons with refractory epilepsy.
Methods: One hundred fifty subjects with intracranial electrodes performed multiple sessions of a free recall memory task; this standardized task controlled for subject attention levels and other unmeasured confounders. We utilized a dominance analysis to rank the importance of subject-specific factors based on their relative influence on IED rates. Linear mixed-effects models were employed to comprehensively examine factors with high ranked importance. Results: Seizure onset zone (SOZ) location, time of testing, and antiseizure medication (ASM) status were highly associated with IED rates. The global IED rate of electrodes in SOZs was 34% higher than the global IED rate of electrodes outside of SOZs (Non-SOZ) (p < 0.001). However, Non-SOZ electrodes had similar averaged IED rates regardless of their anatomical locations (p = 0.99). Subjects on older generation (p < 0.001) and combined generation (p < 0.001) ASM regimens had significant IED rate reductions relative to the group taking no ASMs; newer generation ASM regimens demonstrated a nonsignificant association with IED rates (p = 0.13). Of the ASMs included in this study, the following ASMs significantly reduced IED rates: levetiracetam (p < 0.001), carbamazepine (p < 0.001), lacosamide (p = 0.03), zonisamide (p = 0.01), lamotrigine (p = 0.03), phenytoin (p = 0.03), and topiramate (p = 0.01). Conclusions: We ranked the relative influence that subject-specific factors have on IED rates. Our findings confirmed, with intracranial recordings, that IED rates were higher in regions near SOZs relative to regions distant from SOZs. They also suggest that IED rates may be a new metric to consider when assessing ASM efficacy. In all, we revealed the importance of considering specific factors, such as SOZ location and medication status, when analyzing IEDs for either clinical or research purposes. Funding: Please list any funding that was received in support of this abstract.: This work was supported by the NIH (05-T32LM012204-03; U01NS113198-01), the National Science Foundation (Award #1632738), and a Diamond Foundation Research Development Award.
