Comparing Seizures Captured by Rapid Response EEG and Conventional EEG Recordings in a Multicenter Clinical Study.

Objective: A recent multicenter prospective study (DECIDE trial) examined the use of Ceribell Rapid Response EEG (Rapid-EEG) in the emergent evaluation and management of critically ill patients suspected to have non-convulsive seizures. We present a detailed, patient-level examination of seizures detected either on initial Rapid-EEG or subsequent conventional EEG within 24 h to investigate whether seizures were missed on Rapid-EEG due to the exclusion of midline/parasagittal coverage. Methods: We identified from 164 patients studied in the DECIDE trial those who had seizures detected on Rapid-EEG but not conventional EEG (n = 6), conventional EEG but not Rapid-EEG (n = 4), or both Rapid-EEG and conventional EEG (n = 9). We examined the electrographic characteristics of ictal and interictal findings on both devices, especially their detection in lateral or midline/parasagittal chains, and patient clinical histories to identify contributors toward discordant seizure detection. Results: Seizures detected on both EEG systems had similar electrographic appearance and laterality. Seizures detected only on conventional EEG (within 24 h following Rapid-EEG) were visible in the temporal chains, and external clinical factors (e.g., treatment with anti-seizure medications, sedation, and duration of recordings) explained the delayed presentation of seizures. Patients with seizures detected only by Rapid-EEG were treated with anti-seizure medications, and subsequent conventional EEG detected interictal highly epileptiform patterns with similar laterality. Conclusions: Our case series demonstrates that electrographic data obtained from initial Rapid-EEG and subsequent conventional EEG monitoring are largely concordant relative to morphology and laterality. These findings are valuable to inform future investigation of abbreviated EEG systems to optimize management of suspected non-convulsive seizures and status epilepticus. Future, larger studies could further investigate the value of Rapid-EEG findings for forecasting and predicting seizures in long-term EEG recordings.

Effect of rapid EEG on anti-seizure medication usage

Objective: To study how early diagnoses from rapid EEG (rEEG) during the initial evaluation of patients with suspected non-convulsive seizures correlates with changes in anti-seizure medication (ASM) use. Methods: We performed a retrospective chart review of 100 consecutive adult patients at an academic medical center who underwent rEEG monitoring for suspected non-convulsive seizures. We collected information on the timing of ASM administration and categorized EEG diagnoses as seizures (SZ), highly epileptiform patterns (HEP), or normal or slow activity (NL/SL). We used a χ² test to determine whether the use of ASMs was significantly different between SZ/HEP and NL/SL cases. Results: Of 100 patients, SZ were found in 5%, HEP in 14%, and no epileptiform/ictal activity in 81%. Forty-six percent of patients had received ASM(s) before rEEG. While 84% of HEP/SZ cases were started or continued on ASMs, only 51% of NL/SL cases were started or continued on ASMs after rEEG (χ² [1, n=100] = 7.09, p=0.008). Thirty-seven patients had received sedation (i.e., propofol or dexmedetomidine) prior to rEEG. In 15 patients (13/30 NL/SL, 2/7 HEP/SZ), sedation was discontinued following rEEG. Significance: Our study demonstrates that seizures were rapidly ruled out with rEEG in 81% of patients while 19% of patients were rapidly identified as having seizures or being at higher risk for seizures. The rapid evaluation of patients correlated with a significant reduction in ASM treatment in NL/SL cases compared to HEP/SZ cases. Thus, early access to EEG information may lead to more informed and targeted management of patients suspected to have nonconvulsive seizures.

Introduction of pathogenic mutations into the mouse Psen1 gene by Base Editor and Target-AID.

Base Editor (BE) and Target-AID (activation-induced cytidine deaminase) are engineered genome-editing proteins composed of Cas9 and cytidine deaminases. These base-editing tools convert C:G base pairs to T:A at target sites. Here, we inject either BE or Target-AID mRNA together with identical single-guide RNAs (sgRNAs) into mouse zygotes, and compare the base-editing efficiencies of the two distinct tools in vivo. BE consistently show higher base-editing efficiency (10.0-62.8%) compared to that of Target-AID (3.4-29.8%). However, unexpected base substitutions and insertion/deletion formations are also more frequently observed in BE-injected mice or zygotes. We are able to generate multiple mouse lines harboring point mutations in the mouse presenilin 1 (Psen1) gene by injection of BE or Target-AID. These results demonstrate that BE and Target-AID are highly useful tools to generate mice harboring pathogenic point mutations and to analyze the functional consequences of the mutations in vivo.