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Objective: Despite the availability of pharmacological treatment for seizures, people with epilepsy (PwE) commonly experience impairments in quality of life (QoL). Given the limited access to psychosocial treatments for PwE, digital interventions could bridge treatment gaps and help improve QoL. The objective of this study was to examine the effectiveness of emyna, a fully automated digital intervention based on cognitive behavioral therapy (CBT) techniques, in improving health‐related QoL among PwE who reported impairments in QoL. A previous trial showed that emyna was effective in improving depressive symptoms among PwE with a comorbid depressive disorder, but its effects on QoL among PwE without comorbid depression remain unknown. Methods: A pragmatic randomized controlled trial was conducted with N = 438 PwE (mean age = 37.5, 70.3% women, physician‐verified diagnoses) who were assigned to the intervention group (n = 216), which used emyna alongside treatment as usual (TAU), or the control group (n = 222), which received TAU only. QoL and secondary outcomes such as general self‐efficacy, medication adherence, general distress, and epilepsy‐related work and social adjustment were assessed at baseline, 3 months, and 6 months. The primary outcome was QoL assessed with the Quality of Life in Epilepsy [QOLIE‐31] total score at 3 months post‐randomization. Results: Findings from the intent‐to‐treat analyses showed that after 3 months, participants in the intervention group experienced significant and clinically relevant improvements in health‐related QoL compared to the control group (baseline‐adjusted group difference = 4.5; 95% CI = [2.0, 6.9], p < 0.001; Cohen's d = 0.32). Effects on secondary outcomes did not reach statistical significance. Significance: This study extends previous research by demonstrating that emyna facilitates improvements in QoL in a diverse group of PwE treated in routine care settings. This CBT‐based digital intervention therefore presents a convenient and cost‐effective addition to healthcare providers' treatment repertoire. Plain Language Summary: In our study, we tested a digital program called emyna, which conveys cognitive behavioral therapy (CBT) techniques to help improve the quality of life for people living with epilepsy. We found that those who used emyna alongside their usual treatments felt better about their quality of life compared to those who did not use the program. Emyna offers a new, convenient way for people with epilepsy to manage their condition, which can be used alongside currently available treatments. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to analyze whether the rate of breakthrough seizures in patients taking antiseizure medication (ASM) who have been seizure‐free for at least 12 months varies among different types and etiologies of epilepsy. Given the relative ease of achieving seizure freedom with ASM in patients with post‐ischemic stroke epilepsy, we hypothesized that this etiology is associated with a reduced risk of breakthrough seizures. Methods: We defined a breakthrough seizure as an unprovoked seizure occurring while the patient was taking ASM after a period of at least 12 months without seizures. Data were analyzed retrospectively from a tertiary epilepsy outpatient clinic. Patients were eligible for inclusion if they either had a breakthrough seizure at any time or a seizure‐free interval of at least 2 years. Our primary endpoint was rate of breakthrough seizures. We conducted univariable and multivariable analyses to identify variables associated with breakthrough seizures. Results: Of 521 patients (53% females, median age = 49 years) included, 29% had a breakthrough seizure, which occurred after a median seizure‐free interval of 34 months (quartiles = 22, 62). When controlling for clinically relevant covariates, breakthrough seizures were associated with post‐ischemic stroke epilepsy (odds ratio [OR] =.267, 95% confidence interval [CI] =.075–.946), genetic generalized epilepsy (OR =.559; 95% CI =.319–.978), intellectual disability (OR = 2.768, 95% CI = 1.271–6.031), and the number of ASMs previously and currently tried (OR = 1.203, 95% CI = 1.056–1.371). Of the 151 patients with breakthrough seizures, 34.3% did not reachieve terminal 12‐month seizure freedom at the last visit. Significance: This is the first study to show an association between type and etiology of epilepsy and risk of breakthrough seizures. Our data suggest that epilepsies in which seizure freedom can be obtained more easily also exhibit a lower risk of breakthrough seizures. These findings may help to better counsel seizure‐free patients on their further seizure prognosis. [ABSTRACT FROM AUTHOR]

Background: Epilepsy and other seizure disorders account for a high disease burden in Germany. As a timely diagnosis and accurate treatment are crucial, improving the management of these disorders is important. Outside of Germany, outpatient long-term video EEGs (ALVEEGs) have demonstrated the potential to support the diagnosis and management of epilepsy and other seizure disorders. This study aims to evaluate the implementation of ALVEEGs as a new diagnostic pathway in eastern parts of Germany to diagnose epilepsy and other seizure disorders and to assess if ALVEEGs are equally effective as the current inpatient-monitoring gold standard, which is currently only available at a limited number of specialized centers in Germany. Methods: ALVEEG is a prospective, multicenter, randomized controlled equivalence trial, involving five epilepsy centers in the eastern states of Germany. Patients will be randomized into either intervention (IG) or control group (CG), using a permuted block randomization. The sample size targeted is 688 patients, continuously recruited over the trial. The IG will complete an ALVEEG in a home setting, including getting access to a smartphone app to document seizure activity. The CG will receive care as usual, i.e., inpatient long-term video-EEG monitoring. The primary outcome is the proportion of clinical questions being solved in the IG compared to the CG. Secondary outcomes include hospital stays, time until video EEG, time until diagnosis and result discussion, patients' health status, quality of life and health competence, and number and form of epilepsy-related events and epileptiform activity. Alongside the trial, a process implementation and health economic evaluation will be conducted. Discussion: The extensive evaluation of this study, including an implementation and health economic evaluation, will provide valuable information for health policy decision-makers to optimize future delivery of neurological care to patients affected by epilepsy and other seizure disorders and on the uptake of ALVEEG into standard care in Germany. Trial registration: German Clinical Trials Register (DRKS00032220), date registered: December 11, 2023. [ABSTRACT FROM AUTHOR]

Objective: In temporal lobe epilepsy (TLE), a taxonomy classifying patients into 3 cognitive phenotypes has been adopted: minimally, focally, or multidomain cognitively impaired (CI). We examined gray matter (GM) thickness patterns of cognitive phenotypes in drug‐resistant TLE and assessed potential use for predicting postsurgical cognitive outcomes. Methods: TLE patients undergoing presurgical evaluation were categorized into cognitive phenotypes. Network edge weights and distances were calculated using type III analysis of variance F‐statistics from comparisons of GM regions within each TLE cognitive phenotype and age‐ and sex‐matched healthy participants. In resected patients, logistic regression models (LRMs) based on network analysis results were used for prediction of postsurgical cognitive outcome. Results: A total of 124 patients (63 females, mean age ± standard deviation [SD] = 36.0 ± 12.0 years) and 117 healthy controls (63 females, mean age ± SD = 36.1 ± 12.0 years) were analyzed. In the multidomain CI group (n = 66, 53.2%), 28 GM regions were significantly thinner compared to healthy controls. Focally impaired patients (n = 37, 29.8%) showed 13 regions, whereas minimally impaired patients (n = 21, 16.9%) had 2 significantly thinner GM regions. Regions affected in both multidomain and focally impaired patients included the anterior cingulate cortex, medial prefrontal cortex, medial temporal, and lateral temporal regions. In 69 (35 females, mean age ± SD = 33.6 ± 18.0 years) patients who underwent surgery, LRMs based on network‐identified GM regions predicted postsurgical verbal memory worsening with a receiver operating curve area under the curve of 0.70 ± 0.15. Interpretation: A differential pattern of GM thickness can be found across different cognitive phenotypes in TLE. Including magnetic resonance imaging with clinical measures associated with cognitive profiles has potential in predicting postsurgical cognitive outcomes in drug‐resistant TLE. ANN NEUROL 2024;95:984–997 [ABSTRACT FROM AUTHOR]

Background and purpose: In patients with epilepsy and sustained seizure freedom, guidelines recommend considering discontinuation of antiseizure medication (ASM) based on shared decision‐making. This study aims to identify factors associated with non‐discontinuation of ASM in seizure‐free patients. Methods: Retrospective data from three sites of an academic outpatient clinic were analyzed. Adult patients with epilepsy who have been seizure‐free for ≥24 months on ASM monotherapy were included. The primary end‐point was non‐discontinuation of ASM, defined as no discontinuation or no dose reduction of ≥25% at the last outpatient clinic visit in the ultimate seizure‐free interval. Secondary end‐points included frequency of discussion on discontinuation attempts between patients and physicians, adherence to ASM discontinuation decisions, and post‐discontinuation seizure outcomes. Results: Out of 338 included patients, 81.7% did not discontinue ASM and did not reduce its dose, 11.5% discontinued ASM and 6.8% had a significant dose reduction. Factors independently associated with non‐discontinuation of ASM were history of focal to bilateral or generalized tonic–clonic seizures (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.08–5.06), history of breakthrough seizures (OR 3.32, 95% CI 1.10–10.04), history of failed attempts to discontinue or reduce the ASM dose (OR 4.67, 95% CI 1.03–21.11) and higher ASM load at the index visit (OR 6.10, 95% CI 2.09–17.78). Discontinuation attempts were made during the entire period of seizure freedom and were most commonly undertaken ≥10 years after the last seizure. Conclusions: This study provides insights into factors associated with the shared decision‐making process regarding ASM discontinuation in seizure‐free patients and highlights the importance of considering individual patient characteristics and seizure history. [ABSTRACT FROM AUTHOR]

Neuroinflammation is highly influenced by microglia, particularly through activation of the NLRP3 inflammasome and subsequent release of IL-1β. Extracellular ATP is a strong activator of NLRP3 by inducing K+ efflux as a key signaling event, suggesting that K+-permeable ion channels could have high therapeutic potential. In microglia, these include ATP-gated THIK-1 K+ channels and P2X7 receptors, but their interactions and potential therapeutic role in the human brain are unknown. Using a novel specific inhibitor of THIK-1 in combination with patch-clamp electrophysiology in slices of human neocortex, we found that THIK-1 generated the main tonic K+ conductance in microglia that sets the resting membrane potential. Extracellular ATP stimulated K+ efflux in a concentration-dependent manner only via P2X7 and metabotropic potentiation of THIK-1. We further demonstrated that activation of P2X7 was mandatory for ATP-evoked IL-1β release, which was strongly suppressed by blocking THIK-1. Surprisingly, THIK-1 contributed only marginally to the total K+ conductance in the presence of ATP, which was dominated by P2X7. This suggests a previously unknown, K+-independent mechanism of THIK-1 for NLRP3 activation. Nuclear sequencing revealed almost selective expression of THIK-1 in human brain microglia, while P2X7 had a much broader expression. Thus, inhibition of THIK-1 could be an effective and, in contrast to P2X7, microglia-specific therapeutic strategy to contain neuroinflammation. [ABSTRACT FROM AUTHOR]

• Focal electroclinical features at onset of generalized seizure are well-known. • In contrary, knowledge on generalized onset seizures with focal evolution is sparse. • We report detailed ictal EEG and semiological characteristics of five such patients. • As focal signs may be prominent, risk of misclassification as focal seizure is high. • In generalized onset seizures, focal electroclinical features seem to be a variant. At onset of generalized seizures, focal electroclinical features are commonly seen, while generalized onset seizures with focal evolution (GOFE) are largely unknown bearing the risk of misclassification. In two German epilepsy-centers, patients with GOFE documented by video-EEG monitoring (VEM) between 2017 and 2022 were identified retrospectively. In addition to analysis of ictal electroclinical features, detailed epilepsy and family history, response to antiseizure medication (ASM), and findings from neuroimaging were considered. We identified five patients with GOFE, three females, age 14 to 22 years. All patients developed genetic generalized epilepsy in childhood or adolescence, each presenting with two or three generalized seizure types. In each of the five patients, one GOFE was recorded by VEM. At onset, EEG seizure patterns were characterized by generalized spike-wave discharges at 2.5 to 3.5/ sec for 9 to 16 s followed by focal evolution of the discharges. Interictally, all patients presented with generalized spike-wave discharges without focal abnormalities. Semiology at onset was behavioral arrest in two patients and generalized increase in tone in one, while two onsets were clinically inapparent. Semiological signs during focal evolution were variable, comprising head and body version, figure 4 sign, unilateral arm clonic activity, and staring with oral automatisms. In one case, focality involved both hemispheres successively. Prominent focal semiological features in GOFE carry a high risk of misclassification as focal seizures and epilepsy and thus wrong choice of ASM. This calls for low-threshold VEM if any doubts of focal genesis of seizures exist. [ABSTRACT FROM AUTHOR]