Study Objectives To compare estimated epileptic source localizations from 5 sleep-wake states (SWS): wakefulness (W), rapid eye movement sleep (REM), and non-REM 1-3. Methods Electrical source localization (sLORETA) of interictal spikes from different SWS on surface EEG from the epilepsy monitoring unit at spike peak and take-off, with results mapped to individual brain models for 75% of patients. Concordance was defined as source localization voxels shared between 2-5 SWS, and discordance as those unique to 1 SWS against 1-4 other SWS. Results 563 spikes from 16 prospectively recruited focal epilepsy patients across 161 day-nights. SWS exerted significant differences at spike peak but not take-off. Source localization size did not vary between SWS. REM localizations were smaller in multifocal than unifocal patients (28.8% vs. 54.4%, p=0.0091). All 5 SWS contributed about 45% of their localizations to converge onto 17.0±15.5% voxels. Against any one other SWS, REM was least concordant (54.4% vs. 66.9%, p=0.0006) and most discordant (39.3% vs. 29.6%, p=0.0008). REM also yielded the most unique localizations (20.0% vs. 8.6%, p=0.0059). Conclusions REM was best suited to identify candidate epileptic sources. sLORETA proposes a model in which an “omni-concordant core” of source localizations shared by all 5 SWS is surrounded by a “penumbra” of source localizations shared by some but not all SWS. Uniquely, REM spares this core to “move” source voxels from the penumbra to unique cortex not localized by other SWS. This may reflect differential intra-spike propagation in REM, which may account for its reported superior localizing abilities.
Refractory status epilepticus (RSE) is a life-threatening emergency with high mortality and poor functional outcomes in survivors. Treatment is typically limited to intravenous anesthetic infusions and multiple anti-seizure medications. While ongoing seizures can cause permanent neurological damage, medical therapies also pose severe and life-threatening side effects. We tested the feasibility of using high-definition transcranial direct current stimulation (hd-tDCS) in the treatment of RSE. We conducted 20-min hd-tDCS sessions at an outward field orientation, intensity of 2-mA, 4 + 1 channels, and customized for deployment over the electrographic maximum of epileptiform activity (“spikes”) determined by real-time clinical EEG monitoring. There were no adverse events from 32 hd-tDCS sessions in 10 RSE patients. Over steady dosing states of infusions and medications in 29 included sessions, median spike rates/patient fell by 50% during hd-tDCS on both automated ( p = 0.0069) and human ( p = 0.0277) spike counting. Median spike rates for any given stimulation session also fell by 50% during hd-tDCS on automated spike counting ( p = 0.0032). Immediately after hd-tDCS, median spike rates/patient remained down by 25% on human spike counting ( p = 0.018). Compared to historical controls, hd-tDCS subjects were successfully discharged from the intensive care unit (ICU) 45.8% more often ( p = 0.004). When controls were selected using propensity score matching, the discharge rate advantage improved to 55% ( p = 0.002). Customized EEG electrode targeting of hd-tDCS is a safe and non-invasive method of hyperacutely reducing epileptiform activity in RSE. Compared to historical controls, there was evidence of a cumulative chronic clinical response with more hd-tDCS subjects discharged from ICU. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-022-01317-5.
Background: Subclinical seizures are common in hospitalized patients and require electroencephalography (EEG) for detection and intervention. At our institution, continuous EEG (cEEG) is not available, but intermittent EEGs are subject to constant live interpretation. As part of quality improvement (QI), we sought to estimate the residual missed seizure rate at a typical quaternary Canadian health care center without cEEG. Methods: We calculated residual risk percentages using the clinically validated 2HELPS2B score to risk-stratify EEGs before deriving a risk percentage using a MATLAB calculator which modeled the risk decay curve for each recording. We generated a range of estimated residual seizure rates depending on whether a pre-cEEG screening EEG was simulated, EEGs showing seizures were included, or repeat EEGs on the same patient were excluded. Results: Over a 4-month QI period, 499 inpatient EEGs were scored as low (n = 125), medium (n = 123), and high (n = 251) seizure risk according to 2HELPS2B criteria. Median recording duration was 1:00:06 (interquartile range, IQR 30:40–2:21:10). The model with highest residual seizure rate included recordings with confirmed electrographic seizures (median 20.83%, IQR 20.6–26.6%), while the model with lowest residual seizure rate was in seizure-free recordings (median 10.59%, IQR 4%–20.6%). These rates were significantly higher than the benchmark 5% miss-rate threshold set by 2HELPS2B (p<0.0001). Conclusions: We estimate that intermittent inpatient EEG misses 2–4 times more subclinical seizures than the 2HELPS2B-determined acceptable 5% seizure miss-rate threshold for cEEG. Future research is needed to determine the impact of potentially missed seizures on clinical care.
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