Abstracts

Rationale: Interictal epileptiform discharges (IEDs) are a pathological signature of hyperexcitability in focal human epilepsy. Modulation of IEDs by sleep-wake states has been well documented. Previous studies have demonstrated that non-REM sleep has been associated with increased IED frequency, whereas REM sleep has been associated with decreased IED frequency compared to an awake state. Deep brain stimulation (DBS) is a proven treatment for drug-resistant focal epilepsy and has been shown to decrease seizure frequency; however, its effects on IEDs are poorly understood. Novel DBS devices now enable local field potential (LFP) sensing and IED tracking in ambulatory subjects.


Methods: Continuous LFP recordings were taken in five ambulatory subjects implanted with the Medtronic RC+STM device. IEDs were counted in five-minute bins and saved with the corresponding sleep-wake state. To account for differences in time spent in each sleep-wake state (awake, non-rem and rem sleep) these rates were averaged per one hour of a given sleep-wake state. IED rates were standardized by calculating the Z-score. These standardized scores were then used to compare the effects of sleep-wake state and stimulation pattern on IED rates for all subjects.


Results: Comparison of IED rates in both hemispheres by sleep-wake state reveal decreased IED rates in Awake and REM sleep states compared to non-REM sleep. No statistical significance was observed between Awake and REM sleep IED rates. This pattern held when looking at individual patients, hemispheres, and brain regions. Both high and low frequency stimulation was associated with increased IED rates compared to no stimulation in all sleep-wake states regardless of hemisphere. In the left hemisphere, high frequency stimulation correlated with decreased IED rates compared to low frequency stimulation in all sleep-wake states. Similar effects were seen in the right hemisphere during both awake and REM states.


Conclusions: We demonstrate that, in accordance with previous reports, IED activity is increased in non-REM sleep compared to awake and REM sleep states; however, in contrast, we did not find significantly reduced IED activity in REM sleep compared to an awake state. Additionally, we show that both high and low frequency correlates with increased IED frequency in all sleep-wake states.


Funding: This research was supported by National Institutes of Health (UH2&3-NS95495, R01-NS092882), LQ1605 from the National Program of Sustainability II (MEYS CR, Czech Republic), and institutional resources from Mayo Clinic, Rochester MN USA, Medtronic Plc, Minneapolis, MN, USA.