Stefan Wolking

Objective Electroencephalography (EEG) microstate analysis seeks to cluster the scalp's electric field into semistable topographical EEG activity maps at different time points. Our study aimed to investigate the features of EEG microstates in subjects with focal epilepsy and psychogenic nonepileptic seizures (PNES). Methods We included 62 adult subjects with focal epilepsy or PNES who received video‐EEG monitoring at the epilepsy monitoring unit. The subjects (mean age = 42.8 ± 21.2 years) were distributed equally between epilepsy and PNES groups. We extracted microstates from a 4.4 ± 1.0‐min, 21‐channel resting‐state EEG. We excluded subjects with interictal epileptiform discharges during resting‐state EEGs. After preprocessing, we derived five main EEG microstates—MS1 to MS5—for the full frequency band (1–30 Hz) and frequency subbands (delta, 1–4 Hz; theta, 4–8 Hz; alpha, 8–12 Hz; beta, 12–30 Hz), using the MATLAB‐based EEGLAB toolkit. Statistical features of microstates (duration, occurrence, contribution, global field power [GFP]) were compared between the groups, using logistic regression corrected for age and sex. Results We detected no differences in microstate parameters in the full frequency band. We found a longer duration (delta: B = −7.680, p = .046; theta: B = −16.200, p = .043) and a higher contribution (delta: B = −7.414, p = .035; theta: B = −7.509, p = .031) of MS4 in lower frequency bands in the epilepsy group. The PNES group showed a higher occurrence of MS5 in the delta subband ( B = 3.283, p = .032). In the theta subband, a higher GFP of MS1 was associated with the PNES group ( B = 5.674, p = .025), whereas a higher GFP of MS2 was associated with the epilepsy group ( B = −6.579, p = .026). Significance Microstate features show differences between patients with focal epilepsy and PNES. EEG microstates could be a promising parameter, helping to understand changes in brain dynamics in subjects with epilepsy, and should be explored as a potential biomarker.

Objective Microdeletions are associated with different forms of epilepsy but show incomplete penetrance, which is not well understood. We aimed to assess whether unmasked variants or double CNVs could explain incomplete penetrance. Methods We analyzed copy number variants (CNVs) in 603 patients with four different subgroups of epilepsy and 945 controls. CNVs were called from genotypes and validated on whole‐genome (WGS) or whole‐exome sequences (WES). CNV burden difference between patients and controls was obtained by fitting a logistic regression. CNV burden was assessed for small and large (>1 Mb) deletions and duplications and for deletions overlapping different gene sets. Results Large deletions were enriched in genetic generalized epilepsies (GGE) compared to controls. We also found enrichment of deletions in epilepsy genes and hotspots for GGE. We did not find truncating or functional variants that could have been unmasked by the deletions. We observed a double CNV hit in two patients. One patient also carried a de novo deletion in the 22q11.2 hotspot. Interpretation We could corroborate previous findings of an enrichment of large microdeletions and deletions in epilepsy genes in GGE. We could also replicate that microdeletions show incomplete penetrance. However, we could not validate the hypothesis of unmasked variants nor the hypothesis of double CNVs to explain the incomplete penetrance. We found a de novo CNV on 22q11.2 that could be of interest. We also observed GGE families carrying a deletion on 15q13.3 hotspot that could be investigated in the Quebec founder population.