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Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.

Background and purpose: Infection with COVID‐19 can lead to persistent sequelae, such as fatigue, daytime sleepiness or disturbed sleep, that can remain for more than 12 weeks and that are summarized as post‐COVID syndrome. The causes remain unclear. The present study investigated the presence of sleep disorders in patients with post‐COVID syndrome using polysomnography. Methods: Thirty‐four patients with post‐COVID syndrome and new‐onset fatigue and sleepiness after a SARS‐CoV2 infection underwent polysomnography in accordance with American Association of Sleep Medicine (AASM) standards as part of their clinical workup. Analysis was performed visually based on AASM criteria (scoring manual version 2.6, 2020). Results: Polysomnography revealed a sleep efficiency of <80% in 50% of patients and a mean respiratory disturbance index (RDI) of 9.9 ± 15.4/h. Excluding central apneas, 12 patients (35%) had an RDI of ≥5/h, pointing to obstructive sleep apnea syndrome (OSAS; AASM 2014). Patients with a high RDI were significantly older (p = 0.01) and showed a trend towards a higher body mass index (p = 0.08) than patients with a normal RDI but had no other risk factors for OSAS. Six patients agreed to long‐term treatment of their OSAS and all reported discontinuation of daytime symptoms. Conclusions: Post‐COVID symptoms such as daytime sleepiness, fatigue and memory and concentration problems may in part be a result of reduced sleep efficiency and sleep apnea in a relevant percentage of patients. This possibly treatable cause of the symptoms should be kept in mind in patients presenting with post‐COVID syndrome. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4-0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM-related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology-specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.

Population transmembrane currents and neuronal firing in different layers of the human entorhinal cortex (ER) were recorded during semantic and episodic memory processes using a linear array of 24 laminar microelectrodes. Both measures, as well as local broadband spectral power, increased during retrieval of newly-learned character istics, especially in superficial layers. No differences were observed in the activity evoked by remembering people as compared to places Semantic retrieval evoked similar activity. In contrast, intentional encoding of declarative memory evoked relatively little activity. it double-dissociation of these responses with simultaneously recorded lateral inferotemporal recordings suggests that entorhinal cortex may be specifically engaged during retrieval, across multiple memory types and materials. (c) 2007 Elsevier Inc. All rights reserved.

Aim: Language lateralization with functional transcranial Doppler sonography (fTCD) and lexical word generation has been shown to have high concordance with the Wada test and functional magnetic resonance imaging in adults. We evaluated a nonlexical paradigm to determine language dominance in children. Method: In 23 right-handed children (12 females, 11 males; age range 6-11y; mean age 8y 4mo, SD 1y 7mo) and in 22 adolescents (14 females, 8 males; age range 12-18y; mean age 14y 8mo, SD 2y 5mo) cerebral blood flow velocity (CBFV) was measured in both middle cerebral arteries during picture description and in adolescents additionally during lexical word generation. For each individual/paradigm a lateralization index (LI; side difference in CBFV during mental activity) and its standard error of the mean (SEM; representing variability of the LI throughout task repetition) were computed. Results: Fourteen of 23 children (mean LI = 0.74, SD 4.22; SEM 1.05, SD 0.51) and 14 of 21 adolescents (LI = 2.35, SD 4.65; SEM 1.09, SD 0.61) showed left hemispheric dominance during picture description compared with 20 of 21 adolescents during word generation (LI = 3.72 SD 1.93; SEM 0.99, SD 0.41). Indicated by similarity in mean SEM, variability of the LI throughout task repetition did not differ between age groups or paradigms. Interpretation: Functional TCD proved to be well tolerated in children, with similar data quality as in adolescents. However, the picture description paradigm failed to show left hemispheric dominance in a substantial number of participants. This emphasizes the need to evaluate further paradigms for fTCD language lateralization in children.

Objective: This study was performed to identify coexisting structural lesions in patients with epilepsy and known temporal encephaloceles (TEs). Methods: Forty‐seven structural magnetic resonance imaging (MRI) scans of patients with epilepsy and radiologically diagnosed TEs were retrospectively reviewed visually and using an automated postprocessing software, the Morphometric Analysis Program v2018 (MAP18), to depict additional subtle, potentially epileptogenic lesions in the 3D T1‐weighted MRI data. All imaging findings were evaluated in the context of clinical and electroencephalographical findings. Results: The study population consisted of 47 epilepsy patients (38.3% female, n = 18). The median age at the time of the scan was 40 years (range 12–81 years). Twenty‐one out of 47 MRI scans (44.7%) showed coexisting lesions in the initial MRI evaluation; in 38.3% (n = 18) of patients, those lesions were considered probably epileptogenic. After postprocessing, probable epileptogenic lesions were identified in 53.2% (n = 25) of patients. Malformations of cortical development had initially been reported in 17.0% (n = 8) of patients with TEs, which increased to 38.3% (n = 18) after postprocessing. TEs and other epileptogenic lesions were considered equally epileptogenic in 21.3% (n = 10) of the cases in the initial MR reports and 25.5% (n = 12) of the cases after postprocessing. Significance: Temporal encephaloceles are a potential cause of MRI‐negative temporal lobe epilepsy. According to our data, TEs can occur with other lesions, suggesting that increased awareness is also required in patients with lesional epilepsy. TEs may not always be epileptogenic; hence, their occurrence with other structural pathologies may influence the presurgical evaluation and surgical approach. Finally, TEs can be associated with malformations of cortical development, which may indicate a common developmental etiology of those lesions. [ABSTRACT FROM AUTHOR]

Objective: Despite increased awareness of the serious epilepsy complication sudden unexpected death in epilepsy (SUDEP), a substantial population of people with epilepsy (PWE) remain poorly informed. Physicians indicate concern that SUDEP information may adversely affect patients' health and quality of life. We examined SUDEP awareness and the immediate and long‐term effects of providing SUDEP information to PWE. Methods: Baseline knowledge and behaviors among PWE and behavioral adjustments following the provision of SUDEP information were evaluated in a prospective, multicenter survey using the following validated scales: Neurological Disorders Depression Inventory for Epilepsy for depression symptoms, the EuroQoL five‐dimension scale for health‐related quality of life (HRQoL), a visual analog scale for overall health, the revised Epilepsy Stigma Scale for perceived stigma, and the Seizure Worry Scale for seizure‐related worries. The prospective study collected data through semiquantitative interviews before (baseline), immediately after, and 3 months after the provision of SUDEP information. Results: In total, 236 participants (mean age = 39.3 years, range = 18–77 years, 51.7% women) were enrolled, and 205 (86.9%) completed long‐term, 3‐month follow‐up. One patient died from SUDEP before follow‐up. No worsening symptoms from baseline to 3‐month follow‐up were observed on any scale. At baseline, 27.5% of participants were aware of SUDEP. More than 85% of participants were satisfied with receiving SUDEP information. Three quarters of participants were not concerned by the information, and >80% of participants recommended the provision of SUDEP information to all PWE. Although most patients reported no behavioral adjustments, 24.8% reported strong behavioral adjustments at 3‐month follow‐up. Significance: The provision of SUDEP information has no adverse effects on overall health, HRQoL, depressive symptoms, stigma, or seizure worry among PWE, who appreciate receiving information. SUDEP information provision might improve compliance among PWE and reduce but not eliminate the increased mortality risk. [ABSTRACT FROM AUTHOR]