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Background: Depression is the most common mental illness worldwide and generates an enormous health and economic burden. Furthermore, it is known to be associated with an elevated risk of arteriosclerotic cardiovascular diseases (ASCVD), particularly stroke. However, it is not a factor reflected in many ASCVD risk models, including SCORE2. Thus, we analysed the relationship between depression, ASCVD and SCORE2 in our cohort. Methods: We analysed 9350 subjects from the Paracelsus 10,000 cohort, who underwent both a carotid artery ultrasound and completed a Beck Depression Inventory (BDI) screening. Patients were categorised binomially based on the BDI score. Atherosclerotic carotid plaque or absence was dichotomised for logistic regression modelling. Odds ratios and adjusted relative risks were calculated using Stata. Results: Subjects with an elevated BDI (≥14) had higher odds for carotid plaques compared to subjects with normal BDI, especially after adjusting for classical risk factors included in SCORE2 (1.21; 95%CI 1.03–1.43, p = 0.023). The adjusted relative risk for plaques was also increased (1.09; 95%CI 1.01–1.18, p = 0.021). Subgroup analysis showed an increased odds of plaques with increases in depressive symptoms, particularly in women and patients ≤55 yrs. Conclusions: In our cohort, the BDI score is associated with subclinical atherosclerosis beyond classical risk factors. Thus, depression might be an independent risk factor which may improve risk stratification if considered in ASCVD risk prediction models, such as SCORE2. Furthermore, reminding clinicians to take mental health into consideration to identify individuals at increased atherosclerosis risk may provide added opportunities to address measures which can reduce the risk of ASCVD. [ABSTRACT FROM AUTHOR]

Background: Use of cannabis-based products is becoming more frequent, and it is important that healthcare professionals are informed and confident about them when making evidence-based decisions about their use. This study aimed to gain an international perspective on the attitudes, knowledge, and confidence of healthcare professionals about cannabis-based products. Methods: An online questionnaire regarding these products was completed by 1580 healthcare professionals (neurologists, psychiatrists, general practitioners, pharmacists and nurses) from 16 countries across Asia, Europe, Oceania, South America, and the Middle East. Results: Respondents expressed a high level of interest in cannabis-based products (median score 9 out of 10) and reported that they felt knowledgeable about them (median score 6 out of 7). They reported a high level of confidence when providing patients with information on cannabis-based products, returning median scores of 6 and 5 out of 7 for their legality and regulations, and their benefits and risks, respectively. Despite this, healthcare professionals sought further information on cannabis-based products across areas including legality, neurobiology, and scientific evidence. Finally, 59% (n = 930) of respondents considered robust clinical trial evidence as the most important factor to ensure patient safety in the context of these products. Few nominally significant differences emerged between healthcare professionals from different specialities or regions. Conclusion: In conclusion, this large survey of attitudes held by healthcare professionals towards cannabis-based products revealed a high level of interest and a demand for more information. Limitations of this study include potential sample bias and limited external validity. [ABSTRACT FROM AUTHOR]

Epilepsies are a group of heterogeneous brain disorder, and antiseizure medications (ASMs) are the mainstay of treatment. Despite the availability of more than 30 drugs, at least one third of individuals with epilepsy are drug-resistant. This emphasizes the need for novel compounds that combine efficacy with improved tolerability. A literature review on the pharmacology, efficacy, tolerability, and safety of azetukalner (XEN1101), a second-generation opener of neuronal potassium channels currently in Phase 3 development as ASM. Results from the phase 2b clinical trial strongly support the ongoing clinical development of azetukalner as a new ASM. Its pharmacokinetic properties support convenient once-daily dosing, eliminating the need for titration at initiation or tapering at the conclusion of treatment. CYP3A4 is the main enzyme involved in its metabolism and drug-drug interactions can affect the drug exposure. Preliminary analysis of an ongoing open-label study reveals no reported pigmentary abnormalities. The upcoming Phase 3 clinical trials are expected to provide further insight into the efficacy, tolerability, and safety of azetukalner in treating focal-onset and primary generalized tonic-clonic seizures. Structurally distinct from currently marketed ASMs, azetukalner has the potential to be the only-in-class Kv7.2/7.3 opener on the market upon regulatory approval. [ABSTRACT FROM AUTHOR]

Objective: Status epilepticus (SE) may lead to long‐term consequences. This study evaluated the risk and predictors of seizure occurrence after SE, with a focus on SE due to acute symptomatic etiologies. Methods: Prospectively collected data about adults surviving a first non‐hypoxic SE were reviewed. The outcome was the occurrence of unprovoked seizures during the follow‐up. Kaplan–Meier survival curve analysis and log‐rank test were used to analyze the time to seizure occurrence and determine the statistical significance between etiological groups. Three subcategories within acute etiology were considered according to the presence of the following: (1) structural lesion (acute‐primary); (2) brain involvement during systemic disorders (acute‐secondary); and (3) drug or alcohol intoxication/withdrawal (acute‐toxic). Cox proportional hazards model was adopted to estimate hazard ratios (HRs) with the 95% confidence intervals (CIs). Results: Two hundreds fifty‐seven individuals were included. Fifty‐four subjects (21.0%) developed seizures after a median of 9.9 (interquartile range 4.3–21.7) months after SE. The estimated 1‐, 2‐, and 5‐year rates of seizure occurrence according to acute SE etiologies were 19.4%, 23.4%, and 30.1%, respectively, for acute‐primary central nervous system (CNS) pathology; 2.2%, 2.2%, and 8.7%, respectively, for acute‐secondary CNS pathology; and 0%, 9.1%, and 9.1%, respectively, for acute‐toxic causes. Five‐year rates of seizure occurrence for non‐acute SE causes were 33.9% for remote, 65.7% for progressive, and 25.9% for unknown etiologies. In multivariate Cox regression model, progressive etiology (adjusted HR [adjHR] 2.27, 95% CI 1.12–4.58), SE with prominent motor phenomena evolving in non‐convulsive SE (adjHR 3.17, 95% CI 1.38–7.25), and non‐convulsive SE (adjHR 2.38, 95% CI 1.16–4.90) were independently associated with higher hazards of unprovoked seizures. Older people (adjHR.98, 95% CI.96–.99) and people with SE due to acute‐secondary CNS pathology (adjHR.18, 95% CI.04–.82) were at decreased risk of seizure occurrence. Significance: SE carries a risk of subsequent seizures. Both the underlying cause and epileptogenic effects of SE are likely to contribute. [ABSTRACT FROM AUTHOR]

Background: The transmission of amyloid β (Aβ) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing. Aims: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients. Methods: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review. Results: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4–18, range = 0–26 years) years. The median symptom latency was 39 years (IQR = 34–41, range = 28–49). The median age at symptom onset was 49 years (IQR = 43–55, range = 32–70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures. Conclusions: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients. [ABSTRACT FROM AUTHOR]

The International League Against Epilepsy (ILAE) introduced a classification for seizure types in 2017 and updated the classification for epilepsy syndromes in 2022. These classifications aim to improve communication among healthcare professionals and help patients better describe their condition. So far, regulatory agencies have used different terminology. This paper stresses the crucial need for consistently adopting ILAE terminology in both regulatory processes and clinical practice. It highlights how language plays a significant role in healthcare communication and how standardized terminology can enhance patient comprehension. The ongoing review of guidelines by regulatory bodies offers a timely opportunity. Aligning regulatory terminologies holds the potential to facilitate discussions on future drug development and harmonize practices across diverse regions, ultimately fostering improved care and research outcomes in epilepsy treatment. [ABSTRACT FROM AUTHOR]

Objectives: Although in epilepsy patients the likelihood of becoming seizure‐free decreases substantially with each unsuccessful treatment, to our knowledge this has been poorly investigated in status epilepticus (SE). We aimed to evaluate the proportion of SE cessation and functional outcome after successive treatment steps. Methods: We conducted a post hoc analysis of a prospective, observational, multicenter cohort (Sustained Effort Network for treatment of Status Epilepticus [SENSE]), in which 1049 incident adult SE episodes were prospectively recorded at nine European centers. We analyzed 996 SE episodes without coma induction before the third treatment step. Rates of SE cessation, mortality (in ongoing SE or after SE control), and favorable functional outcome (assessed with modified Rankin scale) were evaluated after each step. Results: SE was treated successfully in 838 patients (84.1%), 147 (14.8%) had a fatal outcome (36% of them died while still in SE), and 11 patients were transferred to palliative care while still in SE. Patients were treated with a median of three treatment steps (range 1–13), with 540 (54.2%) receiving more than two steps (refractory SE [RSE]) and 95 (9.5%) more than five steps. SE was controlled after the first two steps in 45%, with an additional 21% treated after the third, and 14% after the fourth step. Likelihood of SE cessation (p < 0.001), survival (p = 0.003), and reaching good functional outcome (p < 0.001) decreased significantly between the first two treatment lines and the third, especially in patients not experiencing generalized convulsive SE, but remained relatively stable afterwards. Significance: The significant worsening of SE prognosis after the second step clinically supports the concept of RSE. However, and differing from findings in human epilepsy, RSE remains treatable in about one third of patients, even after several failed treatment steps. Clinical judgment remains essential to determine the aggressiveness and duration of SE treatment, and to avoid premature treatment cessation in patients with SE. [ABSTRACT FROM AUTHOR]

Limited guidelines exist regarding osteoporosis prevention in the general population. Despite being a subject of controversy, the majority of research suggests that decreased vitamin D levels correlate with increased bone turnover, that is, an important risk factor for osteoporosis development. In most guidelines, daily vitamin D supplementation is recommended. In persons with epilepsy (PWE), the situation is more complex, as other factors can increase the chance of being vitamin D deficient. Currently, there are no internationally accepted guidelines regarding monitoring bone health in PWE. Our aim was to review the existing evidence in PWE on: (1) risk factors for vitamin D deficiency, (2) the identification of higher risk groups, and (3) the optimal ways to monitor bone health. Our narrative review shows that: (1) anti‐seizure medication (ASM) use, especially enzyme‐inducing ASM (EIASM) and valproic acid, is identified as an important risk factor for impaired bone health (e.g., increased risk for osteoporosis/fractures and/or vitamin D deficiency); (2) higher risk groups within the PWE population are present: intellectual or physical disability, institutionalized patients, puberty, early onset epilepsy and developmental epileptic encephalopathies, postmenopausal women, and use of multiple ASM/concomitant drugs (e.g. corticosteroids); and (3) a monitoring scheme can be suggested including laboratory tests, bone density measurements, managing of risk factors, and/or vitamin D supplementation. Overall, regular vitamin D measurement in PWE is a cost‐effective and practical method for monitoring vitamin D deficiency, whereas in high‐risk patients the combination of vitamin D measurement and bone densitometry is recommended. There is not enough evidence to advocate continuous vitamin D supplementation in all PWE. Children with epilepsy should receive the recommended daily intake of vitamin D for age and additional monitoring and supplementation if at higher risk of deficiency. There is a need for prospective trials exploring the potential benefit of vitamin D supplementation in PWE. [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of patients are subsequently not operated as no focal non-eloquent SOZ can be identified. The 5-SENSE Score is a 5-point score to predict whether a focal SOZ is likely to be identified by SEEG. This study aims to validate the 5-SENSE Score, improve score performance by incorporating auxiliary diagnostic methods and evaluate its concordance with expert decisions., Methods and Analysis: Non-interventional, observational, multicentre, prospective study including 200 patients with drug-resistant epilepsy aged ≥15 years undergoing SEEG for identification of a focal SOZ and 200 controls at 22 epilepsy surgery centres worldwide. The primary objective is to assess the diagnostic accuracy and generalisability of the 5-SENSE in predicting focality in SEEG in a prospective cohort. Secondary objectives are to optimise score performance by incorporating auxiliary diagnostic methods and to analyse concordance of the 5-SENSE Score with the expert decisions made in the multidisciplinary team discussion., Ethics and Dissemination: Prospective multicentre validation of the 5-SENSE score may lead to its implementation into clinical practice to assist clinicians in the difficult decision of whether to proceed with implantation. This study will be conducted in accordance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (2014). We plan to publish the study results in a peer-reviewed full-length original article and present its findings at scientific conferences., Trial Registration Number: NCT06138808., Competing Interests: AA-R has no conflict of interest related to this work. Outside of the submitted work, she acted as a paid consultant for Epilog and received travel support and speaker's honoraria from Eisai. PP has received speaker honoraria or consultancy fees to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus and UCB Pharma, outside the submitted work. He is an Associate Editor for Epilepsia Open. Furthermore, he is supported by an Emerging Leadership Investigator Grant from the Australian National Health and Medical Research Council (APP2017651), The University of Melbourne, Monash University, the Austin Medical Research Foundation and the Norman Beischer Medical Research Foundation. VV has participated in advisory boards and symposium organised by Angellini, Bial, Biocodex, Eisai, Jazz Pharmaceuticals, Novartis, Paladin, Takeda, UCB, Xenon. AU has served as a consultant for Neuropace. JC serves on the scientific advisory board at NeuroOne Medical Technologies. SS received speaker honoraria and consultancy fees from Greenwich, Neurelis, SK Life Science, Bioserenity, Monteris and UCB outside the submitted work. ASM has received speaker honoraria and consultancy fees from Paladin and Jazz Pharmaceuticals, outside the submitted work. GZ gratefully acknowledges the support of the WISS 2025 project ‘IDA-Lab Salzburg’ (20204-WISS/225/197-2019 and 20102-F1901166-KZP). ET reports personal fees from EVER Pharma, Marinus, Argenix his institution has received grants from Biogen, UCB Pharma, Eisai, Red Bull, Merck, Bayer, the European Union, FWF Österreichischer Fond zur Wissenschaftsforderung, Bundesministerium für Wissenschaft und Forschung and Jubilaumsfond der Österreichischen Nationalbank outside the submitted work. BF has no conflict of interest in relation to this work. Outside of this work, she received honoraria for speaking engagements/advisory board meetings from UCB, UNEEG, Paladin labs, Eisai and Natus. Furthermore, she received a project grant from the Canadian Institutes of Health Research (PJT-175056) as well as Start-up Funding from Duke University. All other coauthors report no conflict of interest related to this work., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Scalp-EEG incompletely covers the frontal lobe cortex. Underrepresentation of frontobasal or frontomesial structures, fast ictal spreading, and false lateralization impede scalp-EEG interpretation. Hence, we investigated the significance of scalp-EEG in the presurgical workup of frontal lobe epilepsy., Methods: Using descriptive statistical methods and Pearson chi-squared test for group comparisons, we retrospectively investigated postsurgical outcome, interictal epileptiform discharges (iiEDs), and electrographic seizure patterns on scalp-EEG in 81 consecutive patients undergoing resective epilepsy surgery within the margins of the frontal lobe., Results: Postoperatively, patients with frontopolar iiEDs (n = 7) or concordant frontopolar iiED focus and seizure-onset (n = 2) were seizure free (n = 7/7, Engel Ia). MRI-positive patients with frontopolar iiEDs or frontopolar seizure-onset (n = 1/8 Engel Id, n = 7/8 Engel Ia) underwent surgery without stereo-EEG. Thirteen of 16 patients with frontolateral (n = 8/10, Engel Ia), or left frontobasal (n = 5/6, Engel Ia) seizure-onset undergoing further stereo-EEG, were seizure-free postoperatively. Seizure-onset prevalent over one electrode (n = 37/44 Engel I, p = 0.02), fast activity (FA)/flattening at seizure-onset (n = 29/33 Engel I, p = 0.02), FA/flattening during the seizure (n = 38/46 Engel I, p = 0.05), or focal rhythmic sharp-/spike-/polyspike-and-slow waves during the seizure (n = 24/31, Engel Ia, p = 0.05) were favorable prognostic markers. Interictal polyspike waves (p = 0.006 for Engel Ia) and interictal paroxysmal FA (p = 0.02 for Engel I) were unfavorable prognostic markers., Conclusions: Frontopolar scalp-EEG findings serve as biomarkers for predicting favorable surgical outcome in lesional frontal lobe epilepsy. Consequently, careful analysis of scalp-EEG assists in bypassing stereo-EEG in these patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Clinical Neurophysiology Society.)

Background: Juvenile myoclonic epilepsy (JME) is associated with cortical thinning of the motor areas. The relative contribution of antiseizure medication to cortical thickness is unknown. We aimed to investigate how valproate influences the cortical morphology of JME., Methods: In this cross-sectional study, individuals with JME with and without valproate, with temporal lobe epilepsy (TLE) with valproate and controls were selected through propensity score matching. Participants underwent T1-weighted brain imaging and vertex-wise calculation of cortical thickness., Results: We matched 36 individuals with JME on valproate with 36 individuals with JME without valproate, 36 controls and 19 individuals with TLE on valproate. JME on valproate showed thinning of the precentral gyri (left and right, p<0.001) compared with controls and thinning of the left precentral gyrus when compared with JME not on valproate (p<0.01) or to TLE on valproate (p<0.001). Valproate dose correlated negatively with the thickness of the precentral gyri, postcentral gyri and superior frontal gyrus in JME (left and right p<0.0001), but not in TLE., Conclusions: Valproate was associated with JME-specific and dose-dependent thinning of the cortical motor regions. This suggests that valproate is a key modulator of cortical morphology in JME, an effect that may underlie its high efficacy in this syndrome., Competing Interests: Competing interests: BCP was supported by a scholarship from the Austrian Society of Epileptology, which was not directly related to this project. ET reports personal fees from EVER Pharma, Marinus, Argenx, Arvelle/Angelini, Medtronic, Bial-Portela and Cª, NewBridge, GL Pharma, GlaxoSmithKline, Hikma, Boehringer Ingelheim, LivaNova, Eisai, UCB, Biogen, Genzyme Sanofi, GW Pharmaceuticals/Jazz and Actavis outside the submitted work; his institution has received grants from Biogen, UCB Pharma, Eisai, Red Bull, Merck, Bayer, the European Union, FWF Osterreichischer Fond zur Wissenschaftsforderung, Bundesministerium für Wissenschaft und Forschung and Jubilaumsfond der Österreichischen Nationalbank outside the submitted work. MK has received honoraria from Biocodex, Bial, GE, GSK, LivaNova, Eisai, UCB, Jazz Pharmaceuticals, and research funding from MRC, the Wellcome Trust, ER-UK, the Henry Smith Foundation and the Epilepsy Society. BW received salary support from the German Research Foundation (WA3135/1-1). The remaining authors have no conflicts of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy., Methods: We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep electroencephalography (EEG) and/or video-polygraphy and brain magnetic resonance imaging were collected. Antiseizure medication response was retrospectively assessed by the referring clinician., Results: A large variety of seizure types was reported, although focal seizures were the most common. Encephalopathy related to status epilepticus during slow-wave sleep (ESES)/developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in >25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype-phenotype relationship even between individuals with the same DLG4 variants., Significance: Our study shows that a subgroup of individuals with DLG4-related synaptopathy have DEE, and approximately one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requires proper investigation with sleep EEG., (© 2023 International League Against Epilepsy.)

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English-language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease-modifying" effects. A more-refined terminology to describe precisely these actions needs to be developed., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)