Abstracts

Rationale:
Slow wave activity during sleep (SWA) is a marker of synaptic strength that can track neuronal plastic changes. Recently, we identified increased SWA during sleep in patients with focal epilepsy, which correlated with the frequency of seizures recorded in the Epilepsy Monitoring Unit. In the present study, we wished to confirm and extend our previous findings by correlating sleep SWA with the frequency of seizures of different severity, and compare the effect of secondary generalized seizures (sGTC) vs primary generalized seizures (PGS) on the sleep EEG. 
Method:
47 drug-refractory epileptic patients (32 focal (FE) -25 with temporal foci - and 13 primary generalized (PGE)) underwent 256-electrode overnight high-density EEG recordings (HDEEG) in the Epilepsy Monitoring Unit of the University of Wisconsin, Madison. Patient data were compared to HDEEG sleep data from 47 age- and gender-matched healthy volunteers. EEG recordings were sleep scored using standard AASM criteria then filtered between 0.5-40 Hz. Custom Matlab scripts were used to reject bad channels and bad epochs. HDEEG topographies of whole-night SWA power (i.e. delta power, 1-4 Hz) were computed from clean epochs of stage 2 and 3 sleep then converted to 2D images. Statistical analyses used a random effects approach as implemented in Statistical Parametric Mapping (SPM). First, a 3-level factorial design compared SWA between patient groups and controls. Second, the number of seizures per hour of EMU (either PGS, or for focal patients focal aware [FA], focal with impaired awareness [FIA], and sGTC) were used as covariates in the analysis. A first analysis investigated differences in correlation between SWA and frequency of FA, FIA vs sGTC. A second analysis investigated correlation between SWA and PGS. A third analysis investigated differences in correlation between SWA and frequency of sGTC vs PGS. Results were thresholded at family-wise-error (FWE) correction p< 0.05 in SPM.
Results:
Compared to controls, both patients with FE and PGE displayed widespread increases in sleep SWA in bilateral scalp areas. Compared to FE, PGE patients showed higher increases in sleep SWA in midline areas. In patients with FE, increased seizure frequency (all seizures pooled together) correlated with increased SWA in bilateral temporal areas; frequent sGTC induced higher increases in frontal SWA compared to FA and FIA. In patients with PGE, no significant correlation was seen between PGS frequency and sleep SWA. Direct comparison showed that sGTC frequency in FE was more strongly correlated with increased sleep SWA than frequency of PGS in PGE.
Conclusion:
Our results confirm and extend prior findings suggesting that an abnormal increase in sleep SWA may be a biomarker for epilepsy. Additionally, our results suggest frequent sGTC may lead to the strongest maladaptive changes in patients with FE. Differences in correlation with sleep SWA also suggest that sGTC might have different underlying mechanisms compared to PGS.
Funding:
:Tiny Blue Dot Foundation & Lily's Fund for Epilepsy Research