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Background: The epileptogenic properties of white matter lesions (WML) in cerebral small vessel disease (CSVD) are not yet understood. The aim of our systematic review and meta-analysis was to estimate the association between the extent of WML in CSVD and epilepsy, analyze whether these WML are associated with an increased risk of seizure recurrence, and evaluate if treatment with anti-seizure medication (ASM) is justified in first-seizure patients with WML and no cortical lesions. Methods: Following a pre-registered study protocol (PROSPERO-ID CRD42023390665), we systematically searched Pubmed and Embase for relevant literature comparing WML load between patients with epilepsy and controls as well as studies on seizure recurrence risk and ASM therapy in the presence vs. absence of WML. We calculated pooled estimates using a random effects model. Results: Eleven studies comprising 2983 patients were included in our study. Presence of WML (OR 2.14, 95% CI 1.38–3.33) and presence of relevant WML as assessed by visual rating scales (OR 3.96, 95% CI 2.55–6.16) but not WML volume (OR 1.30, 95% CI 0.91–1.85) were significantly associated with seizures. These results stayed robust in sensitivity analyses restricted to studies on patients with late-onset seizures/epilepsy. Only two studies assessed the association between WML and risk of seizure recurrence with conflicting results. Currently, there are no studies on the efficacy of ASM therapy in the presence of WML in CSVD. Conclusions: This meta-analysis suggests an association between presence of WML in CSVD and seizures. More research is needed addressing the association between WML and risk of seizure recurrence and ASM therapy focusing on a population of patients with a first unprovoked seizure. [ABSTRACT FROM AUTHOR]

Objective The need for alternative pharmacologic strategies in treatment of epilepsies is pressing for about 30% of patients with epilepsy who do not experience satisfactory seizure control with present treatments. In temporal lobe epilepsy ( TLE) even up to 80% of patients are pharmacoresistant, and surgical resection of the ictogenic tissue is only possible for a minority of TLE patients. In this study we investigate purinergic modulation of drug-resistant seizure-like events ( SLEs) in human temporal cortex slices. Methods Layer V/ VI field potentials from a total of 77 neocortical slices from 17 pharmacoresistant patients were recorded to monitor SLEs induced by application of 8 mM [K+] and 50 μ m bicuculline. Results Activating A1 receptors with a specific agonist completely suppressed SLEs in 73% of human temporal cortex slices. In the remaining slices, incidence of SLEs was markedly reduced. Because a subportion of slices can be pharmacosensitive, we tested effects of an A1 agonist, in slices insensitive to a high dose of carbamazepine (50 μ m). Also in these cases the A1 agonist was equally efficient. Moreover, ATP and adenosine blocked or modulated SLEs, an effect mediated not by P2 receptors but rather by adenosine A1 receptors. Significance Selective activation of A1 receptors mediates a strong anticonvulsant action in human neocortical slices from pharmacoresistant patients. We propose that our human slice model of seizure-like activity is a feasible option for future studies investigating new antiepileptic drug ( AED) candidates. [ABSTRACT FROM AUTHOR]

Purpose: Anxiety and depression are frequent comorbidities in people with epilepsy (PWE), but possible gender differences are often neglected. The aim of the present study was to analyze if men and women with epilepsy differ with regard to anxiety and depressive symptoms and to identify possible predictors.Methods: Adult consecutive PWE (N=302; 53% women) completed self-report questionnaires, including the depression module of the Patient Health Questionnaire (PHQ-9), the anxiety module of the Hospital Anxiety and Depression Scale (HADS-A) and the subscales "medication effects" and "seizure worry" of the Patient-weighted Quality of Life in Epilepsy Inventory-31-P (QOLIE-31-P).Results: There was no gender difference in extent of anxiety (p=.532), which was mainly due to higher anxiety levels in men compared to the general population. The gender difference in depressive symptoms was significant (p=.009), with female patients being more affected. The most important predictors for anxiety and depressive symptoms were detrimental effects of medication (QOL medication effects) and of seizure worry (QOL seizure worry). Moreover, these predictors were more closely associated with anxiety and depressive symptoms in men.Conclusion: Future intervention studies could show whether providing more information about the illness and medication effects may improve anxiety and depression. Our results suggest that such interventions should be tailored to the different needs of men and women. [ABSTRACT FROM AUTHOR]

New treatment approaches in epilepsy – such as novel antiepileptic drugs and neurostimulation – generally at first are assessed in animal models in regard to feasibility, efficacy and safety. The aim of this review was to elucidate and summarize the available literature on in vivo experimental studies on radiofrequency thermoablation and laser interstitial thermal therapy. We have found two in vivo studies on radiofrequency ablation of an acute seizure focus, one assessed the conventional transcranial and the other one a transvenous approach. All other studies focused on technical issues of functional ablation of brain structures assessing parameters such as maximal temperature and duration of thermal ablation as well as electrode devices. As the concept of functional ablation is evident – destruction of the epileptogenic focus as performed in “open” resective surgery – general “proof of concept” experiments do not seem to be necessary. [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: https://doi.org/10.1007/s00415-021-10634-2 [ABSTRACT FROM AUTHOR]

Drug resistant patients undergoing epilepsy surgery have a good chance to become sensitive to anticonvulsant medication, suggesting that the resected brain tissue is responsible for drug resistance. Here, we address the question whether P-glycoprotein (Pgp) and multidrug resistance-associated proteins (MRPs) expressed in the resected tissue contribute to drug resistance in vitro. Effects of anti-epileptic drugs [carbamazepine (CBZ), sodium valproate, phenytoin] and two unspecific inhibitors of Pgp and MRPs [verapamil (VPM) and probenecid (PBN)] on seizure-like events (SLEs) induced in slices from 35 hippocampal and 35 temporal cortex specimens of altogether 51 patients (161 slices) were studied. Although in slice preparations the blood brain barrier is not functional, we found that SLEs predominantly persisted in the presence of anticonvulsant drugs (90%) and also in the presence ofVPM and PBN (86%). Following subsequent co-administration of anti-epileptic drugs and drug transport inhibitors, SLEs continued in 63% of 143 slices. Drug sensitivity in slices was recognized either as transition to recurrent epileptiform transients (30%) or as suppression (7%), particularly by perfusion with CBZ in PBN containing solutions (43, 9%). Summarizing responses to co-administration from more than one slice per patient revealed that suppression of seizure-like activity in all slices was only observed in 7% of patients. Patients whose tissue was completely or partially sensitive (65%) presented with higher seizure frequencies than those with resistant tissue (35%). However, corresponding subgroups of patients do not differ with respect to expression rates of drug transporters. Our results imply that parenchymal MRPs and Pgp are not responsible for drug resistance in resected tissue. [ABSTRACT FROM AUTHOR]

Objective: Identifying factors associated with surgical decision‐making is important to understand reasons for underutilization of epilepsy surgery. Neurologists' recommendations for surgery and patients' acceptance of these recommendations depend on clinical epilepsy variables, for example, lateralization and localization of seizure onset zones. Moreover, previous research shows associations with demographic factors, for example, age and sex. Here, we investigate the relevance of patients' psycho‐social profile for surgical decision‐making. Methods: We prospectively studied 296 patients from two large German epilepsy centers. Multiple logistic regression analyses were used to investigate variables linked to neurologists' recommendations for and patients' acceptance of surgery or intracranial video‐electroencephalographic monitoring. Patients' psycho‐social profiles were assessed via self‐reports and controlled for various clinical–demographic variables. Model selection was performed using the Akaike information criterion. Results: As expected, models for neurologists' surgery recommendations primarily revealed clinical factors such as lateralization and localization of the seizure onset zone, load with antiseizure medication (ASM), and site of the epilepsy‐center. For this outcome, employment was the only relevant psycho‐social aspect (odds ratio [OR] =.38, 95% confidence interval [CI] =.13–1.11). In contrast, three of the five relevant predictors for patients' acceptance were psycho‐social. Higher odds were found for those with more subjective ASM adverse events (OR = 1.04, 95% CI =.99–1.00), more subjective seizure severity (OR = 1.12, 95% CI = 1.01–1.24), and lower subjective cognitive impairment (OR =.98, 95% CI =.96–1.00). Significance: We demonstrated the relevance of the patients' psycho‐social profile for decision‐making in epilepsy surgery, particularly for patients' decisions. Thus, in addition to clinical–demographic variables, patients' individual psycho‐social characteristics add to the understanding of surgical decision‐making. From a clinical perspective, this calls for individually tailored counseling to assist patients in finding the optimal treatment option. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake. [ABSTRACT FROM AUTHOR]

Several studies have suggested high predictive values of serum procalcitonin (PCT) for the discrimination of bacterial and viral meningitis in children and adults. Here, we report PCT serum concentrations in 12 adults suffering from bacterial meningitis. PCT on admission was normal (≤ 500 pg/ml) in 3 and between 500 and 1,000 pg/ml in 2 patients without evidence of concurrent bacterial infections. Conversely, in 5 patients with PCT concentrations between 2,268 and 38,246 pg/ml other infections were present. PCT concentrations were higher with typical meningitis agents (pneumococci and meningococci 12,679 ± 13,092 pg/ml vs. other bacteria 4048 ± 9187 pg/ml, p = 0.041) whilst in nosocomial bacterial meningitis after neurosurgery (n = 3) serum PCT remained normal. We believe that PCT is of limited diagnostic value in adults suffering from bacterial meningitis, especially in cases due to unusual agents or of nosocomial origin. Elevated PCT in bacterial meningitis may indicate the presence of bacterial inflammation outside the central nervous system. [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]

• The SES is important for cognition and mental distress in focal epilepsy. • Neuropsychology needs to consider individual and structural SES. • Successful treatment includes multidisciplinary work and addressing social issues. Epilepsy is often associated with low socioeconomic status (SES). People with epilepsy (PWE) also suffer from cognitive dysfunction and mental distress. In the general population, these constraints are related to individual and structural SES. However, in PWE, cognitive dysfunction and mental distress have been mainly attributed to biological factors such as brain lesions or pharmacological treatment, whereas comprehensive studies on possible social determinants are missing. Here, we study associations of individual and structural SES with cognition and mental distress in PWE. We retrospectively studied 340 adult patients with pharmacoresistant focal epilepsy from Berlin treated at a tertiary epilepsy center. Individual SES (education, employment, and income), structural SES (social index of district and neighborhood), and their interactions were examined. Associations between social variables and verbal learning, psychomotor speed, and mental distress were analyzed with multiple regression analyses, controlling for demographic and medical variables and intelligence. Our sample had lower educational levels and lived more frequently in low SES neighborhoods compared to the general population of Berlin. Thirty percent showed reduced verbal learning, 31% had deficits in psychomotor speed, and 20% revealed significant mental distress. Lower structural SES was related to lower psychomotor speed (Δ R 2 = 0.9%) and higher mental distress (Δ R 2 = 1.6%). Employment was related to verbal learning (Δ R 2 = 0.7%) and psychomotor speed (Δ R 2 = 1.2%). Income and education were linked to mental distress (Δ R 2 = 5%). Neighborhood and individual SES covered more than half of the explained variance in mental distress. Furthermore, interactions between individual and structural SES were identified. We confirm cognitive deficits, significant mental distress, and individual and structural social disadvantage in PWE. Our findings indicate that individual and structural SES are related to cognitive and emotional well-being beyond demographic and medical characteristics. As a clinical implication, individual and structural SES should be considered when interpreting neuropsychological findings. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance 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.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.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.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]

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]

The computational capabilities of neuronal networks are fundamentally constrained by their specific connectivity. Previous studies of cortical connectivity have mostly been carried out in rodents; whether the principles established therein also apply to the evolutionarily expanded human cortex is unclear. We studied network properties within the human temporal cortex using samples obtained from brain surgery. We analyzed multineuron patch-clamp recordings in layer 2-3 pyramidal neurons and identified substantial differences compared with rodents. Reciprocity showed random distribution, synaptic strength was independent from connection probability, and connectivity of the supragranular temporal cortex followed a directed and mostly acyclic graph topology. Application of these principles in neuronal models increased dimensionality of network dynamics, suggesting a critical role for cortical computation. [ABSTRACT FROM AUTHOR]

Background: Electroencephalography (EEG) significantly contributes to the neuroprognostication after resuscitation from cardiac arrest. Recent studies suggest that the prognostic value of EEG is highest for continuous recording within the first days after cardiac arrest. Early continuous EEG, however, is not available in all hospitals. In this observational study, we sought to evaluate the predictive value of a 'late' EEG recording 5–14 days after cardiac arrest without sedatives. Methods: We retrospectively analyzed EEG data in consecutive adult patients treated at the medical intensive care units (ICU) of the Charité—Universitätsmedizin Berlin. Outcome was assessed as cerebral performance category (CPC) at discharge from ICU, with an unfavorable outcome being defined as CPC 4 and 5. Results: In 187 patients, a 'late' EEG recording was performed. Of these patients, 127 were without continuous administration of sedative agents for at least 24 h before the EEG recording. In this patient group, a continuously suppressed background activity < 10 µV predicted an unfavorable outcome with a sensitivity of 31% (95% confidence interval (CI) 20–45) and a specificity of 99% (95% CI 91–100). In patients with suppressed background activity and generalized periodic discharges, sensitivity was 15% (95% CI 7–27) and specificity was 100% (95% CI 94–100). GPDs on unsuppressed background activity were associated with a sensitivity of 42% (95% CI 29–46) and a specificity of 92% (95% CI 82–97). Conclusions: A 'late' EEG performed 5 to 14 days after resuscitation from cardiac arrest can aide in prognosticating functional outcome. A suppressed EEG background activity in this time period indicates poor outcome. [ABSTRACT FROM AUTHOR]

• We report the co-normalized reliability of psycho-social measures. • Reference values for reliable change in a German population are provided. • Psycho-social constructs in PWE have common but also unique variance. • We recommend the weighted QOLIE-31-P scales and the Total score as indicator of QoL. People with epilepsy (PWE) not only suffer from seizures but also from various psycho-social issues containing facets such as social functioning, anxiety, depression or stigmatization, and consequently quality of life. (1) Assessing reliable change of these issues is crucial to evaluate their course and potential treatment effects. As most psycho-social self-report questionnaires have been validated in separate samples, their clinical-socio-demographic differences may limit the comparability and generalizability of the scales' internal consistency, which is important for the reliable change index (RCI). Using a co-normalized approach, we provide the internal consistency and RCIs for a large set of questionnaires targeting quality of life (QOLIE-31-P), depressive symptoms (NDDI-E), anxiety (GAD-7), seizure severity (LSSS), subjective antiseizure medication adverse events (LAEP), stigma, epilepsy-related fear, and restrictions in daily life (PESOS), and subjective cognition (FLei). As for some German versions of these measures, psychometric data is still missing, we also add important information for the German language area. (2) In addition, knowledge about intercorrelations of these constructs is needed to shape questionnaire usage and treatment approaches. We thus investigate associations of these scales and compare weighted and unweighted subscales of the QOLIE-31-P. In our prospective study, 202 adult in-patients of the Epilepsy-Center Berlin-Brandenburg with a reliable diagnosis of epilepsy filled out a set of self-report questionnaires between 03/2018 and 03/2021. We calculated Cronbach's α, RCIs, and bivariate intercorrelations and compared the respective correlations of weighted and unweighted scales of the QOLIE-31-P. For most of the scales, good to excellent internal consistency was identified. Furthermore, we found intercorrelations in the expected directions with strong links between scales assessing similar constructs (e.g., QOLIE-31-P Cognition and FLei), but weak relationships between measures for different constructs (e.g., QOLIE-31-P Seizure worry and FLei). The QOLIE-31-P Total score was highly correlated with most of the other scales. Some differences regarding their correlational patterns for weighted and unweighted QOLIE-31-P scales were identified. Psycho-social constructs share a large amount of common variance, but still can be separated from each other. The QOLIE-31-P Total score represents an adequate measure of general psycho-social burden. [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]

Objective: Epilepsy with generalized tonic–clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients. Methods: In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors. Results: We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13–22) and a median follow‐up duration of 10 years (IQR = 5–20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2‐year remission was 24 months (IQR = 24–46.5) with a median number of 1 (IQR = 1–2) ASM. During the long‐term follow‐up (i.e., 202 patients followed ≥5‐years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no‐remission and relapsing–remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic–clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12‐month follow‐up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression. Significance: GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations. [ABSTRACT FROM AUTHOR]

Highlights • Meaningful mental distress was present in about one fifth of patients with TLE. • Severity of mental distress highly correlated with symptoms of depression (r s = 0.80). • Mental distress and depression were not related to cognitive impairment in TLE. • Depression and cognitive impairment may have different pathogenic mechanisms in TLE. Abstract Objective Cognitive impairment and depression often co-exist among patients with epilepsy. However, there is still debate whether depression and cognition are related in patients with temporal lobe epilepsy (TLE). Even if they were related, it is still unclear whether symptoms of depression specifically, or rather symptoms of mental distress in general, have a negative impact on cognition in patients with TLE. In the present study, we examined whether self-rated symptoms of mental distress and of depression are related to different cognitive functions in unilateral TLE. Methods We retrospectively studied 162 patients undergoing preoperative evaluation for epilepsy surgery (95 patients with left TLE (LTLE) and 67 patients with right TLE (RTLE)). Severity of mental distress and symptoms of depression were measured with the Symptom Checklist-90-Revised (SCL-90-R) and the Beck Depression Inventory (BDI), respectively. Bivariate correlations were calculated between these two measures and neuropsychological measures of verbal recall, figural learning, psychomotor speed, and phonemic word fluency. Due to multiple testing, a corrected level of p < 0.0063 was regarded as significant, only. Results Seventeen and 19% of patients reported meaningful mental distress and meaningful symptoms of depression, respectively. Mental distress highly correlated with symptoms of depression (r s = 0.80). We found no significant correlations of either mental distress or symptoms of depression with measures of cognitive function. Conclusions In contrast to some former studies with smaller sample sizes, the present study could not detect a relationship of depression with cognitive impairment in patients with unilateral TLE. Likewise, mental distress and cognition were unrelated in our sample of patients. Our results may argue against theoretical models claiming a causal link between depression and cognitive impairment or a common pathogenic mechanism for these conditions in patients with TLE. [ABSTRACT FROM AUTHOR]

Background: Acute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications. It was hypothesized that after a first acute symptomatic seizure of structural etiology, the cumulative 12-month risk of unprovoked seizure relapse is ≤ 25%. Methods: Inclusion criteria were age ≥ 18 and acute symptomatic first-ever epileptic seizure; patients with status epilepticus were excluded. Using telephone and mail interviews, participants were followed for 12 months after the acute symptomatic first seizure. Primary endpoint was the occurrence and timing of a first unprovoked seizure relapse. In addition, neuro-intensivists in Germany were interviewed about their antiseizure treatment strategies through an anonymous online survey. Results: Eleven of 122 participants with structural etiology had an unprovoked seizure relapse, resulting in a cumulative 12-month risk of 10.7% (95%CI, 4.7%–16.7%). None of 19 participants with a non-structural etiology had a subsequent unprovoked seizure. Compared to structural etiology alone, combined infectious and structural etiology was independently associated with unprovoked seizure relapse (OR 11.1; 95%CI, 1.8–69.7). Median duration of antiseizure treatment was 3.4 months (IQR 0–9.3). Seven out of 11 participants had their unprovoked seizure relapse while taking antiseizure medication; longer treatment durations were not associated with decreased risk of unprovoked seizure relapse. Following the non-representative online survey, most neuro-intensivists consider 3 months or less of antiseizure medication to be adequate. Conclusions: Even in case of structural etiology, acute symptomatic seizures bear a low risk of subsequent unprovoked seizures. There is still no evidence favoring long-term treatments with antiseizure medications. Hence, individual constellations with an increased risk of unprovoked seizure relapse should be identified, such as central nervous system infections causing structural brain damage. However, in the absence of high-risk features, antiseizure medications should be discontinued early to avoid overtreatment. [ABSTRACT FROM AUTHOR]

Objective: Many people with epilepsy report subjective cognitive impairment (SCI), i.e., problems with memory, attention, or executive functions, reducing quality of life. Nevertheless, overlap with objective cognitive impairment (OCI) is often weak. One reason may be a domain‐specific mismatch between subjective reports and objective tests. We aimed to evaluate relations between SCI and OCI of corresponding domains and to assess whether these differ between persons who over‐ or underestimate their performance. Methods: In this prospective, cross‐sectional sample of 104 adult inpatients with epilepsy, we performed multiple regression analyses predicting SCI in the domains attention, memory, and executive functions. We tested relationships with measures of psychomotor speed, short‐term memory, verbal learning, verbal delayed recall, and word fluency while controlling for age, sex, seizure frequency, structural lesions, mono‐ versus polytherapy and adverse events of antiseizure medication (ASM), depressive and anxiety symptoms, level of education, and employment status. Furthermore, we tested whether these relationships differed between realistic raters and over‐ and underestimators. Results: We found domain‐specific relations for attention and executive functions for the full sample, explaining a small proportion of variance of SCI (general dominance index =.03 and.004), whereas ASM adverse events and psychological variables were more important predictors. When dividing the sample according to the concordance of SCI and OCI, we found high frequencies of both over‐ (23%–46%) and underestimation (31%–35%) depending on the domain. The explanatory power of OCI for SCI was stronger within the subgroups compared to the full sample, suggesting nonlinear relationships and different underlying mechanisms for realistic raters, underestimators, and overestimators. Significance: Domain‐specific SCI and OCI are related, and both should be assessed with standardized instruments. These relationships differ between over‐ and underestimators as well as realistic raters. Based on the concordance of self‐ratings and objective measures, tailored counseling and treatment should be offered. [ABSTRACT FROM AUTHOR]

Women show better performance than men on a range of episodic memory tasks. Evidence regarding a neuroanatomical localization of this effect remains ambiguous. It has been suggested that anterior temporal lobe structures are responsible for sex differences in verbal memory, yet temporal lobe epilepsy (TLE) and TLE surgery do not affect women’s verbal memory advantage. Instead, frontal lobe regions may be relevant for female verbal memory superiority, i.e. by enabling more efficient encoding and retrieval strategies in women. The aim of the present study was to investigate whether women’s verbal memory advantage can be found in patients with frontal lobe epilepsy (FLE), and how patients with FLE and those with TLE differ with regard to sex differences in verbal memory. Fifty patients with unilateral FLE (26 women, 24 men) were compared with 183 patients with unilateral TLE (90 women, 93 men) on both verbal learning and delayed memory. We found that women showed better verbal memory than men in the TLE group, but not in the FLE group. In addition, we found that patients with TLE showed worse verbal learning than those with FLE. Our findings support the idea that women’s advantage in verbal memory may be related to frontal lobe function. [ABSTRACT FROM AUTHOR]

Background: In patients with drug-resistant focal epilepsy, resective surgery is the most successful treatment option to achieve seizure freedom. However, a surprisingly high rate of patients declines their physicians' recommendation to undergo removal of the seizure focus or—if necessary—further video-EEG monitoring (VEM). Methods: In this prospective study, consecutive patients in presurgical assessment with at least one scalp VEM between 2016 and 2018 were included. We assessed both epilepsy-related and psychosocial variables as well as decision-making of physicians and patients, including reasons for decline in the latter. Results: Out of 116 patients with a total of 165 VEM, 20 patients were eventually found to be ineligible for resection, 51 declined, and 45 agreed on recommendations for resection or further VEM diagnostics. Patients most frequently declined due to general fear of brain surgery (n = 30, 59%) and currently lower seizure frequency (n = 11, 22%). An independent predictor of patients' decline was less epilepsy-related fear (OR 0.43; p = 0.02) assessed in a standardised questionnaire. Conclusion: Half of the patients potentially eligible for resective surgery decline the operation or further VEM procedures. Patients who decline are more fearful of brain surgery than of ongoing disabling seizures. More insight is needed to improve counselling of patients. [ABSTRACT FROM AUTHOR]