Search

Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive. There is a critical need for effective inhibitory optogenetic tools that are highly light-sensitive and capable of suppressing neuronal activity in deep brain tissue. In this study, we developed a highly sensitive moderately K + -selective channelrhodopsin (HcKCR1-hs) by molecular engineering of the recently discovered Hyphochytrium catenoides kalium (potassium) channelrhodopsin 1. Transcranial activation of HcKCR1-hs significantly prolongs the time to the first seizure, increases survival, and decreases seizure activity in several status epilepticus mouse models. Our approach for transcranial optogenetic inhibition of neural hyperactivity may be adapted for cell type-specific neuromodulation in both basic and preclinical settings., Competing Interests: Competing interests: K.S., X.D. C.Z. and Y.W. have filed a patent application related to this work. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Introduction: The seizures in Lennox-Gastaut syndrome are typically resistant to treatment. Seven antiseizure medications (ASMs) in the US (six in the UK/EU) are licensed for the treatment of seizures in LGS: lamotrigine, topiramate, rufinamide, clobazam, felbamate (not licensed in the UK/EU), cannabidiol and fenfluramine. Other options include neurostimulation, corpus callosotomy and dietary therapies, principally the ketogenic diet and its variants. New treatments and therapeutic strategies are needed to improve management of both seizures and cognitive/behavioral comorbidities in LGS., Areas Covered: Embase and Medline were searched for articles published between 1 January 2014 and 21 August 2024 reporting efficacy data for pharmacological, neurostimulation, surgical and dietary interventions in individuals with LGS focusing on recent advances. Ongoing and prospective studies were identified from the National Library of Medicine register of clinical trials., Expert Opinion: LGS remains a difficult-to-treat epilepsy. Although no major breakthroughs have been reported, several established and novel ASMs, some surgical strategies and other treatment approaches are of benefit or are showing promise. Progress remains incremental but any improvements in the management of this resistant epilepsy syndrome are worthwhile.

Objective: This study aimed to investigate the effect of a walking program based on the COM-B Behavior Change Model on self-management, anxiety, stress, depression, quality of life, and seizure frequency in individuals with epilepsy., Methods: A prospective, parallel-group controlled experimental design and mixed methods were used. A total of 78 individuals with epilepsy were included in the study and randomly assigned to the intervention (n = 38) and control (n = 40) groups. The intervention group participated in a weekly, twice-a-week, walking program for 12 weeks. The program was based on the COM-B model, focusing on increasing individuals' capability, opportunity, and motivation levels. The control group received standard treatment. Self-management, anxiety, stress, depression, and quality of life were measured using scales. Seizure frequency was measured using daily logs. Qualitative data was collected through semi-structured interviews with 10 participants to understand barriers to walking in individuals with epilepsy., Results: Qualitative data revealed time constraints, lack of motivation, and safety concerns as barriers to walking participation. After a 12-week intervention, a significant increase in self-management levels, a significant decrease in anxiety, stress, and depression levels, a significant improvement in quality of life, and a significant reduction in seizure frequency were observed in the intervention group. No significant changes were observed in these variables in the control group., Conclusion: This study demonstrated that a walking program based on the COM-B Behavior Change Model had a positive impact on self-management, mental health, and quality of life in individuals with epilepsy and may help reduce seizure frequency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) has been shown to be effective in treating some patients with medically refractory epilepsy. However, it remains unknown how seizures spread through the ANT relative to other thalamic nuclei. This study aimed to investigate, through simultaneous recordings from both ANT and pulvinar (PLV) nucleus, their roles in seizure propagation. Our goal was to determine whether the ANT is the primary site of seizure propagation in the human thalamus, especially for focal seizure originating in the medial temporal lobe., Methods: In a retrospective design, we studied EEGs and clinical notes of patients with refractory epilepsy who were implanted with stereo-EEG (sEEG) electrodes across cortical regions, some of which were extended to reach various sites of the thalamus (i.e., multisite thalamic recordings). We selected patients from the Stanford Comprehensive Epilepsy Center with both ANT and PLV electrodes and collected information about the timing and anatomy of seizure activity in the seizure onset zones, usually temporal, and the 2 thalamic sites., Results: We recruited 17 (5 female, mean age 32 years) adult patients with simultaneous ipsilateral ANT and PLV recordings. In all patients, the procedure was safe without any complications. In 100% of patients, the thalamus was involved during seizures (in 88% both ANT and PLV and in 82% first the PLV). In patients with confirmed hippocampal or amygdalar onset seizures, 62% had initial involvement and 100% had subsequent involvement of the PLV nucleus. Only 31% showed initial propagation to ANT. All focal-to-bilateral tonic-clonic seizures and most of the focal impaired awareness seizures had early involvement of both ANT and PLV, with rapid spread to the contralateral nuclei., Discussion: sEEG of thalamic nuclei simultaneously provides an opportunity to understand propagation patterns of seizures with respect to each thalamic subdivision at the individual level. The patterns of seizure propagation, as we report here, provide insights about the prominent involvement of the PLV nucleus during seizure propagation. This may motivate future prospective work in larger cohorts of patients to understand how thalamic propagation may predict response to resective/ablative surgery or whether personalization of DBS (for instance, PLV instead of, or together with, ANT) could improve clinical outcomes.

Background: Patients with convulsive seizures constitute a significant group in acute neurology. No common European clinical practice guidelines on prehospital seizure management exist, and today most patients are brought to hospital for seizure treatment, with great variation in which prehospital treatment is provided. Only 33 % of status epilepticus patients receive a benzodiazepine as first anti-seizure medication (ASM). The aim of this study is to assess the prehospital seizure control protocols in the Emergency Medical Services (EMS) in Norway, and compare these with current evidence for acute management., Method: We performed a descriptive analysis of the 18 regional EMS protocols in Norway and compared the findings with recent evidence on prehospital treatment. We analysed recommended drug and dosage, route of medication administration, number of additional rescue doses permitted, requirements for registration of type of seizures and seizure duration., Results: The protocols vary in terms of preferred medication, administration method, dosage and recommendations regarding first- and second-line therapies. 33 % of protocols explicitly define status epilepticus according to contemporary guidelines, and 16.7 % have an operational definition of when to administer benzodiazepines. All protocols showed variations in dosing and administration instructions and only 28 % had a clearly stated first line treatment., Conclusion: There are disparities in the prehospital seizure management protocols within the Norwegian healthcare system, a system comparable to other European countries. To improve seizure management there is a need for standardised guidelines for prehospital treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Treatment trials for functional seizure (FS) help improve functioning and reduce disability in affected individuals. Clinical trials have prioritized clinician-defined outcomes, but no studies have directly asked adults with FS what they hope to accomplish. This study examined patient-defined goals for treatment in a consecutive cohort of 826 adults with FS referred for outpatient treatment. Goals were reviewed and sorted into 6 categories with 32.5% of goals related to seizure management, 21.8% to abstract functional improvement, 20.3% to concrete functional improvement, 14.8% to seizure education, 10.1% to psychiatry tools, and 0.5% to Other. Although treatment trials have prioritized reduced event frequency as a primary outcome, people with FS most frequently prioritize goals for functional improvement. Data suggests that rehabilitation metrics of FS treatment outcome may be just as, or more important to adults with FS than what medical providers prioritize for outcome success. Study findings have implications for how to define FS treatment success and suggest equal prioritization of patient-centered goals to medically-defined goals in trial design., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The optimal rate of rewarming after therapeutic hypothermia is unclear. Slow rewarming may reduce cardiovascular instability and rebound seizures, but there is little controlled evidence to support this. The present study aimed to determine whether slow rewarming can improve neuroprotection after 72 h of hypothermia. Fetal sheep (0.85 gestation) received sham occlusion (n = 8) or 30 min of global cerebral ischaemia followed by normothermia (n = 7), or hypothermia from 3 to 72 h with either fast, spontaneous rewarming within 1 h (n = 8) or slow rewarming at 0.5°C h -1 over 10 h (n = 8). Hypothermia improved EEG and spectral edge recovery, with no significant difference between fast and slow rewarming. Hypothermia reduced the number of seizures, with no significant difference in seizure activity between fast and slow rewarming. Hypothermia improved neuronal survival in the cortex, CA1, CA3, CA4 and dentate gyrus regions of the hippocampus, with no significant difference between fast and slow rewarming. Hypothermia attenuated microglia counts in the cortex, with no significant difference between fast and slow rewarming. The rate of rewarming after a clinically relevant duration of hypothermia did not affect neurophysiological recovery, neuronal survival or attenuation of microglia after global cerebral ischaemia in term-equivalent fetal sheep. KEY POINTS: The rate of rewarming after 72 h of hypothermia did not affect recovery of EEG or spectral edge. There was no difference in the occurrence of seizures as a result of the rate of rewarming after hypothermia. The rate of rewarming after 72 h of hypothermia did not affect neuronal survival in the cortex or hippocampus., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Objectives: To evaluate the effect of vagus nerve stimulation (VNS) on seizure control, cognitive functions, and quality of life in individuals with drug-resistant epilepsy., Methods: An extensive search of electronic databases was carried out in order to carry out this systematic review. The databases Google Scholar, Embase, PubMed, and the Cochrane Library were searched first to carryout gray literature. To reduce the quantity of pointless studies in the advanced search, the search is limited to "human studies" and "English language" publications only. Combining keywords and Medical Subject Headings (MeSH) terms like ("Vagus Nerve Stimulation" OR "VNS") AND ("Epilepsy" OR "Seizure Control") AND ("Cognitive Function" OR "Quality of Life"). Studies that have been published up to November 30/2023 were included., Results: The search strategy yielded a total of 392 relevant studies. The mean age of participant's ranges from 11 years to 33 years. The duration of follow-up ranging from 6 to 36 months. Eleven studies were included in the review. The mean≥50% response rate after VNS therapy was 56.94% ranged from 48.90% to 83.00%. Four and three studies provided information about Quality of Life in Epilepsy Inventory (QOLIE-31) and The Liverpool Seizure Severity Scale (LSSS) questionnaires respectively., Significance: Epilepsy is a chronic disease characterized by sudden abnormal discharge of brain neurons, which leads to transient brain dysfunction and the presence of spontaneous recurrent seizures. Vagus nerve stimulation has recently been proposed as a potential tool in the treatment of seizure, depressive symptoms, and cognitive impairments. There has been variation in the effects of VNS treatment on seizure control, cognitive functions, and quality of life among patients with drug-resistant epilepsy. So, a comprehensive review of exciting literature is important to see the pooled effect. Previous systematic review and meta-analysis papers were mostly randomized control trial type with specific diseases. The use of a wider variety of study designs than only randomized controlled trials is important. So, we included retrospective and prospective cohort studies in addition to randomized control trials. This enables a more thorough assessment of the connection between quality of life, cognitive function, and vagus nerve stimulation. In addition, the paper looks at a wide range of disease kinds and patterns. We have established a uniform and comprehensive approach throughout the selected studies by mandating the inclusion of all three crucial parameters: vagus nerve stimulation, cognitive function, and quality of life., Plain Language Summary: This systematic review examined 392 relevant studies on vagus nerve stimulation (VNS) therapy, with participants ranging from 11 to 33 years old and follow-up durations of 6-36 months. Eleven studies were included, and the mean response rate after VNS therapy was 56.94%, ranging from 48.90% to 83.00%. The review also reported on quality of life and cognitive function, and seizure severity frequency result from several studies., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Deep brain stimulation, particularly low-frequency stimulation (LFS) targeting fiber tracts, has emerged as a potential therapy for drug-resistant epilepsy (DRE) and for generalized epilepsy, both of which pose significant treatment challenges. LFS diffusely suppresses seizures in the cortex when applied to fiber tracts like the corpus callosum (CC). Nevertheless, the specific processes responsible for suppressing epileptic activity in the cortex induced by LFS remain unclear. This study investigates the mechanisms underlying the antiepileptic effect in the cortex of LFS of the CC in coronal rodent brain slices., Methods: An in vitro 4-aminopyridine (4-AP) seizure model of cortical seizures was generated. LFS stimulation parameters were optimized to provide the largest antiepileptic effect in the cortex when applied to the CC. Changes to tissue excitability and percent time spent seizing were measured due to LFS in artificial cerebrospinal fluid, 4-AP, and in the presence of various specific and nonspecific γ-aminobutyric acid type B (GABA B ) and slow afterhyperpolarization (sAHP) antagonists., Results: LFS significantly suppressed seizure activity in the cortex, with an optimal frequency of 5 Hz (76.5%). Tissue excitability during LFS reduces across a wide range of interstimulus intervals, with a maximum reduction at 200 ms. Notably, the tissue excitability remains depressed at 1000 ms. LFS, in the presence of GABA B antagonists, had diminished seizure reduction (<15%) and failed to reduce tissue excitability in the 50-400-ms range. Tissue excitability measured with paired pulses in the 600-1000-ms range was depressed in the presence of GABA B antagonists, suggesting a different antiepileptic mechanism was active. Upon administering sAHP antagonists, seizure reduction was once again diminished (<15%). Upon administration of both sAHP and GABA B antagonists, LFS failed to provide any meaningful seizure reduction (<5%)., Significance: LFS of the CC provides an antiepileptic effect in the cortex with well-understood mechanisms and could be an alternative to surgical intervention for patients suffering from DRE., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Patients with traumatic brain injury (TBI) often present with seizures (functional and/or epileptic), but treatments for patients with TBI and seizures are limited. We examined treatment phase and 1-year post-enrollment outcomes following neurobehavioral therapy (NBT) for patients with TBI + functional seizures (FS) and TBI + epilepsy., Methods: In this multicenter, prospective, three-group, nonrandomized, controlled trial, with 1-year post-enrollment follow-up, three cohorts of adults were recruited: TBI + video-electroencephalography (EEG)-confirmed FS (n = 89), TBI + EEG-confirmed epilepsy (n = 29), and chart/history-confirmed TBI without seizures (n = 75). Exclusion criteria were recent psychotic or self-injurious behavior, current suicidal ideation, pending litigation or long-term disability, active substance use disorder, and inability to participate in study procedures. TBI + FS and TBI + epilepsy groups completed NBT for seizures, an evidence-based, 12-session, multimodal psychotherapy, whereas TBI without seizures participants received standard medical care. The primary outcome was change in seizure frequency; secondary outcomes were changes in mental health, TBI-related symptoms, disability, and quality of life., Results: Reductions in average monthly seizures occurred during treatment in TBI + FS participants (p = .002) and were significant from baseline (mean = 16.75; 95% confidence interval [CI] = 11.44-24.53) to 12 months post-enrollment (mean = 7.28, 95% CI = 4.37-12.13, p = .002, d = .38). Monthly seizures decreased during treatment in TBI + epilepsy participants (p = .002); reductions were not statistically significant from baseline (mean = 2.38, 95% CI = 1.12-5.04) to 12-month postenrollment (mean = .98, 95% CI = .40-2.42, p = .07, d = .22). Regarding treatment-phase changes in secondary outcome measures, TBI + FS participants improved significantly on 10 of 19 variables (52.6%), TBI + epilepsy participants improved on five of 19 (26.3%), and TBI-only comparisons improved on only one of 19 (5.3%)., Significance: NBT benefited patients with TBI + FS and TBI + epilepsy. Improvements were demonstrated at 1 year post-enrollment in those with TBI + FS. NBT may be a clinically useful treatment for patients with seizures., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Neonatal seizures (NS) represent an important clinical manifestation among critically ill infants and are often the first sign of underlying brain injury. Early recognition and treatment are essential to reduce morbidity and mortality. The present study investigated the NS management and treatment approaches employed by level II/III neonatal intensive care units (NICUs) across the United States to identify areas of consensus and variability., Methods: Personnel associated with level II/III NICUs were directly surveyed with an electronic questionnaire. Access to neurology specialists, on-site electroencephalography (EEG) monitoring, and use of antiseizure medications was directly queried. A total of 51 NICUs participated in this survey., Results: Twenty-five percent of the surveyed NICUs reported having an established clinical practice pathway available for treating NS. Twenty-four percent endorsed having written guidelines that provided a formal definition for the concept of "neonatal seizures." Although the majority of NICUs reported having phenobarbital available for rapid seizure management, most NICUs lacked access to additional antiseizure medications for treatment escalation. Twenty-four percent of the surveyed NICUs had no access to EEG monitoring available to them on-site. Daytime and overnight access to neurology consultants was limited and variable., Conclusions: Findings were consistent with a lack of equitable access for NS treatment. Areas of potential improvement include development and implementation of a protocol for rapidly treating NS that emphasizes enhanced access to EEG and rapid neurology consultation, acknowledging and improving upon resource limitations. These developments may eventually provide earlier detection, evaluation, and treatment of seizures in newborns, contributing to improved long-term outcomes., Competing Interests: Declaration of competing interest The authors declare no known conflicts of interest associated with this publication., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study aims to understand diagnosis communication experiences and preferences of youths with functional seizures and their parents., Methods: Semistructured interviews with youths and their parents from a tertiary care children's hospital were conducted separately. We confirmed the diagnosis of functional seizures with the youth's treating providers. All interviews were audio recorded and professionally transcribed. Two coders performed thematic analysis and determined themes., Results: Thirteen youths (aged 12 to 18) and 13 parents completed interviews separately. Themes included the following: (1) both parents and youths reported substantial fear about their symptoms, diagnosis, prognosis, and treatment options; (2) good communication skills highlighted included providing reassurance, listening, and allowing time for questions, with different preferences between youths and parents in the mode of communication; (3) poor communication for both youths and parents included use of medical jargon, brevity of communication especially with the youth, minimization of youth's symptoms, lack of apparent compassion, and lack of written materials to supplement discussions; (4) perspectives on the role of mental health in functional seizures were heterogeneous, yet concrete treatment plans were desired including access to behavioral therapy; and (5) youths and parents wanted practical guidance including plans for school and how to respond to functional seizures in all settings., Conclusions: Youths and parents provided concrete recommendations for optimal diagnosis communication. Study findings will inform the future development of an educational intervention to improve communication and create a supportive environment for youths with functional seizures., Competing Interests: Declaration of Competing Interest Dr. Kerr writes paid review articles for Medlink Neurology on topic; is a paid consultant for SK Lifesciences, Biohaven Pharmaceuticals, Cerebral Therapeutics, UCB, EpiTel, and the Epilepsy Study Consortium; and has collaborative or data use agreements with Eisai, Janssen, Radius Health, GlaxoSmithKline (GSK), Johnson & Johnson, and Jazz Pharmaceuticals. The remaining authors have no conflicts of interest to declare. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This article examines the value of medical technology through the case of electroencephalograms (EEGs), devices used to visualize brain activity and diagnose seizures. Drawing on ethnographic fieldwork, the article shows that EEGs are valued differently by patients and medical practitioners. While practitioners value EEGs for their clinical utility, i.e., ability to inform clinical decisions, patients value EEGs even in the absence of clinical utility. Indeed, patients derive long-lasting therapeutic effects from this diagnostic technology. These findings intervene in the utilitarian calculus of therapeutic value-a mode of reasoning that equates value with clinical utility-commonly deployed in biomedicine and engineering and call for a recognition of alternative notions such as the therapeutic value of being witnessed and cared for by medical experts via EEGs and other technologies that require time to work. Expansive notions of therapeutic value are imperative for including marginalized patients-especially low-income, disabled, and women patients-in debates on automation and the future of healthcare. Studying how multiple stakeholders value a medical technology provides insight into valuation, objectification, expertise, and other concerns central to science and technology studies., Competing Interests: Declaration of conflicting interestsThe author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective. This study proposes a closed-loop brain-machine interface (BMI) based on spinal cord stimulation to inhibit epileptic seizures, applying a semi-supervised machine learning approach that learns from Local Field Potential (LFP) patterns acquired on the pre-ictal (preceding the seizure) condition. Approach. LFP epochs from the hippocampus and motor cortex are band-pass filtered from 1 to 13 Hz, to obtain the time-frequency representation using the continuous Wavelet transform, and successively calculate the phase lock values (PLV). As a novelty, the Z -score-based PLV normalization using both modified k -means and Davies-Bouldin's measure for clustering is proposed here. Consequently, a generic seizure's detector is calibrated for detecting seizures on the normalized PLV, and enables the spinal cord stimulation for periods of 30 s in a closed-loop, while the BMI system detects seizure events. To calibrate the proposed BMI, a dataset with LFP signals recorded on five Wistar rats during basal state and epileptic crisis was used. The epileptic crisis was induced by injecting pentylenetetrazol (PTZ). Afterwards, two experiments without/with our BMI were carried out, inducing epileptic crisis by PTZ in Wistar rats. Main results. Stronger seizure events of high LFP amplitudes and long time periods were observed in the rat, when the BMI system was not used. In contrast, short-time seizure events of relative low intensity were observed in the rat, using the proposed BMI. The proposed system detected on unseen data the synchronized seizure activity in the hippocampus and motor cortex, provided stimulation appropriately, and consequently decreased seizure symptoms. Significance. Low-frequency LFP signals from the hippocampus and motor cortex, and cord spinal stimulation can be used to develop accurate closed-loop BMIs for early epileptic seizures inhibition, as an alternative treatment., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objectives: With a projected rise in care home residency and the disproportionate impact of epilepsy and seizures on older adults, understanding seizure-related needs in this population is crucial. Data silos and inconsistent recording of residence status make this challenging. We thus leveraged ambulance data to investigate seizure call-out incidence, characteristics, management and costs in care homes compared with the wider community., Design: Retrospective analysis of dispatch data from a regional English ambulance service over four 9-month periods between 2014/2015 and 2021/2022. Suspected seizures in adults (≥16 years) were identified, with data on location, patient age, severity and management extracted. Incidence rates, trends over time and case characteristics were compared. Costs of ambulance response were estimated, and factors influencing emergency department (ED) conveyance were analysed using logistic regression., Setting: North West Ambulance Service National Health Service Trust, serving an adult population of ~5.5 million., Participants: Dispatch data for 98 752 suspected seizure cases., Results: Care homes, accommodating ~0.8% of the regional population, accounted for 7.2% of seizure call-outs. Incidence was higher in care homes than the wider community (55.71 vs 5.97 per 1000 person/year in 2021/2022) and increased over time. Care home cases peaked around 8:00-9:00. Despite similar or lower severity, they had a higher ED conveyance rate (78.3% vs 70.6%). Conveyance likelihood was influenced by factors beyond severity: reduced in homes specialising in learning disabilities (adjusted OR=0.649) and increased in homes with nursing provision (adjusted OR=1.226). Care homes accounted for 7.26% of the £24 million cost., Conclusions: This study highlights the growing seizure-related needs in care homes. Despite similar severity, most cases result in ED conveyance. Future research should examine the appropriateness and implications of these transfers, ensuring specialist services support the care home population effectively., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Transcranial direct current stimulation (tDCS) has garnered significant interest for its potential to enhance cognitive functions and as a therapeutic intervention in various cognitive disorders. However, the clinical application of tDCS has been hampered by significant variability in its cognitive outcomes. Furthermore, the widespread use of tDCS has raised concerns regarding its safety and efficacy, particularly in light of our limited understanding of its underlying neural mechanisms at the cellular level. We still do not know 'where', 'when' and 'how' tDCS modulates information encoding by neurons, in order to lead to the observed changes in cognitive functions. Without elucidating these fundamental unknowns, the root causes of its outcome variability and long-term safety remain elusive, challenging the effective application of tDCS in clinical settings. Addressing this gap, our study investigates the effects of tDCS, applied over the dorsolateral prefrontal cortex, on cognitive abilities and individual neuron activity in macaque monkeys performing cognitive tasks. Like humans performing a delayed match-to-sample task, monkeys exhibited practice-related slowing in their responses (within-session behavioural adaptation). Concurrently, there were practice-related changes in simultaneously recorded activity of prefrontal neurons (within-session neuronal adaptation). Anodal tDCS attenuated both these behavioural and neuronal adaptations when compared with sham stimulation. Furthermore, tDCS abolished the correlation between response time of monkeys and neuronal firing rate. At a single-cell level, we also found that following tDCS, neuronal firing rate was more likely to exhibit task-specific modulation than after sham stimulation. These tDCS-induced changes in both behaviour and neuronal activity persisted even after the end of tDCS stimulation. Importantly, multiple applications of tDCS did not alter burst-like firing rates of individual neurons when compared with sham stimulation. This suggests that tDCS modulates neural activity without enhancing susceptibility to epileptiform activity, confirming a potential for safe use in clinical settings. Our research contributes unprecedented insights into the 'where', 'when' and 'how' of tDCS effects on neuronal activity and cognitive functions by showing that modulation of the behaviour of monkeys by the tDCS of the prefrontal cortex is accompanied by alterations in prefrontal cortical cell activity ('where') during distinct trial phases ('when'). Importantly, tDCS led to task-specific and state-dependent alterations in prefrontal cell activities ('how'). Our findings suggest a significant shift from the view that the effects of tDCS are merely attributable to polarity-specific shifts in cortical excitability and instead propose a more complex mechanism of action for tDCS that encompasses various aspects of cortical neuronal activity without increasing burst-like epileptiform susceptibility., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

DIAGNOSTIC MANAGEMENT OF FIRST SEIZURE AND EPILEPSY. Diagnosis of a first seizure and epilepsy is complex. It is a source of error, with a risk of over or under-diagnosis. A clear understanding of the stages in the diagnostic process is essential, particularly for practitioners dealing with patients in acute situations where the diagnosis has not yet been made: general practitioners, paediatricians, geriatricians, emergency physicians, intensive care specialists... The French National Authority for Health has recently proposed an update of these diagnostic management steps., Competing Interests: L’auteure déclare avoir participé à des interventions ponctuelles pour UCB, Eisai, Angelini Pharma, Neuraxpharm, Jazz et avoir été prise en charge, à l’occasion de déplacements pour congrès, par UCB, Eisai, Angelini Pharma.

Background and Objectives: The purpose of this study was to develop national consensus based on expert opinion on the optimal outpatient care model of pediatric psychogenic nonepileptic seizures (PNES)., Methods: A core working group (CWG) within the PNES special interest group of the Pediatric Epilepsy Research Consortium was established. The CWG developed a rigorous scoring rubric to select experts in pediatric PNES within the United States of America and a three-round Delphi study was conducted to assess consensus on key components of the management of pediatric PNES in the outpatient setting., Results: Eighteen experts representing neurology, psychology, psychiatry, social work and nursing participated in the study. Strong consensus was reached that the multidisciplinary clinic (MDC) model is the gold standard for the outpatient management of pediatric PNES. Consensus was obtained that a neurologist, psychologist and social worker are essential members of the MDC and in the setting of unlimited resources, psychiatry and nursing are also recommended. Further consensus was established on the roles of specific personnel, structure of the clinic, billing practices, trainee inclusion, patient inclusion and exclusion, and end of visit management. While consensus was reached that a new term should be developed for this diagnosis, consensus was not reached on the ideal term., Discussion: Expert consensus was established for the multidisciplinary management of pediatric PNES in the outpatient setting. Specific recommendations were provided that can facilitate the development and implementation of MDCs in other institutions. Further prospective studies are warranted to validate this practice model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

EEG is useful for evaluation of pathophysiology and prognostication of neurocritically ill patients, as it provides non-invasive, real-time monitoring of cerebral function. There have been recently a lot of advances in research on critical care EEG according to the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. Based on the latest knowledge, this review discusses clinical utilization of EEG in neurocritically ill patients, including critical care continuous EEG monitoring, and key points of interpretation of critical care EEG, classifying main purposes into three points: detection of electrographic and electroclinical seizures, consideration of special encephalopathies, and evaluation and prognostication of cerebral function. Neurologists should have fundamental ability to read and interpret critical care EEG and support treating physicians in terms of therapeutic strategy.

Background: Electroconvulsive therapy (ECT) is an important treatment for several severe psychiatric conditions, yet its precise mechanism of action remains unknown. Increased inhibition in the brain after ECT seizures, mediated by γ-aminobutyric acid (GABA), has been linked to clinical effectiveness. Case series on epileptic patients report a postictal serum concentration increase of the GABA A receptor agonist allopregnanolone. Serum allopregnanolone remains unchanged after a full ECT series, but possible transient effects directly after a single ECT seizure remain unexplored. The primary aim was to measure serum concentrations of allopregnanolone and its substrate progesterone after one ECT seizure. Secondary aims were to examine whether concentrations at baseline, or postictal changes, either correlate with seizure generalization or predict clinical outcome ratings after ECT., Methods: A total of 130 participants (18-85 years) were included. Generalization parameters comprised peak ictal heart rate, electroencephalographic (EEG) seizure duration, and prolactin increase. Outcome measures were ratings of clinical global improvement, perceived health status and subjective memory impairment. Non-parametric tests were used for group comparisons and correlations. The prediction analyses were conducted with binary logistic and simple linear regression analyses., Results: Allopregnanolone and progesterone remained unchanged and correlated neither with seizure generalization nor with clinical outcome. In men (n = 50), progesterone increased and allopregnanolone change correlated negatively with EEG seizure duration. In a subgroup analysis (n = 62), higher baseline allopregnanolone and progesterone correlated with postictal EEG suppression., Conclusions: ECT seizures have different physiologic effects than generalized seizures in epilepsy. Progesterone might have implications for psychiatric illness in men., (© 2024. The Author(s).)

Objective: To assess the impact of vagus nerve stimulation (VNS) on quality of life contributors such as rescue medications., Methods: Using the seizure diary application SeizureTracker™ database, we examined trends in rescue administration frequency before and after the first recorded VNS magnet swipe in patients with drug-resistant epilepsy who had 1) At least one VNS magnet swipe recorded in the diary, and 2) Recorded usage of a benzodiazepine rescue medication (RM) within 90 days prior to the first swipe. A paired Wilcoxon rank-sum test was used to assess changes in RM usage frequency between 30-, 60-, 90-, 180- and 360-day intervals beginning 30 days after first magnet swipe. Longitudinal changes in RM usage frequency were assessed with a generalized estimating equation model., Results: We analyzed data of 95 patients who met the inclusion criteria. Median baseline seizure frequency was 8.3 seizures per month, with median baseline rescue medication usage frequency of 2.1 administrations per month (SD 3.3). Significant reductions in rescue medication usage were observed in the 91 to 180 day interval after first VNS magnet swipe, and at 181 to 360 days and at 361 to 720 days, with the magnitude of reduction increasing over time. Decreases in rescue medication usage were sustained when controlling for patients who did not record rescue medication use after the first VNS magnet swipe (N=91). Significant predictors of reductions in rescue medication included baseline frequency of rescue medication usage and time after first VNS magnet swipe., Significance: This retrospective analysis suggests that usage of rescue medications is reduced following the start of VNS treatment in patients with epilepsy, and that the magnitude of reduction may progressively increase over time., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [SW, CRM & PM reported personal fees (speakers bureau) from LivaNova outside the submitted work. R.M. is the cofounder/owner of Seizure Tracker, LLC, which has received funding from Courtagen, Engage Therapeutics, Greenwich Biosciences, Neurelis, UCB, Xenon Pharmaceuticals, and grants from TuberousSclerosis Alliance. SC is the co-founder/owner of EpilepsyAI, LLC, which has received funding from Neurelis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential Competing Interest.]., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Management of severe (drug-resistant) epilepsy and epilepsy in other serious illnesses is multidimensional and requires consideration of both physical symptoms and psychosocial distress that require individualized treatment. Palliative care offers a holistic approach to disease that focuses on all dimensions of suffering to maintain quality of life. Integration of a palliative care mind- and skillset in the management of severe epilepsy and epilepsy in other serious illnesses can provide person-centered care and support for families and caregivers., Competing Interests: A.-C.W. is a member of the “International Neuropalliative Society” (INPCS), the “Deutsche Gesellschaft für Neurologie” (DGN), “Deutsche Gesellschaft für Palliativmedizin” (DGP), and “Klinische DGN-Kommission für neurologische Palliativmedizin.” A.-C.W. received a research grant from DGfE. A.B.K. is the chair of the reference group neurology & palliative care of the European Association for Palliative Care, and a member of the INPCS, DGN, and DGfE., (Thieme. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: Although most cases of pediatric convulsive status epilepticus start in the prehospital setting, many patients do not receive treatment. The use of prehospital seizure rescue medications by caregivers is crucial, but studies suggest a lack of proper training on medication use., Methods: We created a novel proof of principle mannequin and simulation for training proper administration of rectal diazepam, with a scoring paradigm to standardize and assess the educational process., Results: Twenty-three health care providers (nurses and nurse practitioners, residents/fellows, and attending physicians) and 5 patient guardians/parents were included in the study. The rectal diazepam simulator displayed a high degree of physical and emotional realism (mean ≥ 4/5 on Likert scale survey) that effectively decreased time to treatment (-12.3 seconds; SD, 16.3) and improved the accuracy of medication delivery in a simulation setting (-4.2 points; SD, 3.1). The scoring technique had appropriate interrater reliability (≥86% on all but 2 prompts) and was a feasible instrument to assess the effectiveness of the educational intervention., Conclusions: A unique procedure-focused child simulator and rescue medication score offer an innovative and effective means to train caregivers on the use of lifesaving seizure rescue medications., Competing Interests: The other authors declare no conflict of interest., (Copyright © 2023 Society for Simulation in Healthcare.)

This study proposes a charge-mode neural stimulator for electrical stimulation systems that utilizes a capacitor-reuse technique with a residual charge detector and achieves active charge balancing simultaneously. The design is mainly used for epilepsy suppression systems to achieve real-time symptom relief during seizures. A charge-mode stimulator is adopted in consideration of the complexity of circuit design, the high voltage tolerance of transistors, and system integration requirements in the future. The residual charge detector allows users to understand the current stimulus situation, enabling them to make optimal adjustments to the stimulation parameters. On the basis of the information on actual stimulation charge, active charge balancing can effectively prevent the accumulation of mismatched charges on electrode impedance. The capacitor- and phase-reuse techniques help realize high integration of the overall stimulator circuit in consideration of the commonality of the use of a capacitor and charging/discharging phase in the stimulation circuit and charge detector. The proposed charge-mode neural stimulator is implemented in a TSMC 0.18 µm 1P6M CMOS process with a core area of 0.2127 mm 2 . Measurement results demonstrate the accuracy of the stimulation's functionality and the programmable stimulus parameters. The effectiveness of the proposed charge-mode neural stimulator for epileptic seizure suppression is verified through animal experiments.

Background: Randomized controlled clinical trials (RCTs) investigating cognitive-behavioral therapy (CBT) among adults with functional seizures (FS) have become increasingly available, prompting the opportunity to critically appraise the efficacy and safety of CBT in this population., Methods: We conducted a systematic review and meta-analysis including RCTs comparing CBT in addition to standardized medical treatment (SMT) versus SMT alone for adults with FS. The primary outcome was seizure freedom at the end of treatment. Secondary outcomes included measures of quality of life, anxiety and depression assessed via standardized clinical questionnaires., Results: Three RCTs were included comprising 228 participants treated with CBT and 222 with SMT. The intervention was significantly associated with seizure freedom (Odds Ratio [OR] 1.98; 95 % confidence interval [CI] 1.14, 3.46; p = 0.02; I2 = 0 %), reductions in anxiety (standardized mean difference [SMD] -0.21; 95 % CI -0.41, -0.003; p = 0.047; I2 = 0 %) and improvements in quality of life (SMD 0.34; 95 % CI 0.12, 0.57; p = 0.003; I2 = 0 %) at the end of treatment. Conversely, no significant differences between groups were observed in depression symptoms (SMD -0.19; 95 % CI -0.39, 0.02; p = 0.08; I 2  = 0 %). There was no statistically significant increase in the risk of suicidal ideation and self-harm with CBT (OR 2.11; 95 % CI 0.81, 5.48; p = 0.13; I 2  = 0 %) nor were there differences in terms of discontinuation rates during follow-up (OR 0.92; 95 % CI 0.49, 1.72; p = 0.79; I 2  = 7 %)., Conclusions: There is high-quality evidence supporting the efficacy and safety of CBT in treating FS. Future research should investigate whether combining CBT with other therapeutic methods could potentially enhance treatment efficacy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PM, SL and ECI report no disclosures relevant to this manuscript. CPB reports personal fees from UCB A/S (honorary scientific talks and teaching), personal fees from EISAI A/S (honorary for scientific talks and teaching), and other from Arvelle (honorary for scientific talks/teaching and travel support) outside the submitted work. CDB reports personal fees from UCB Pharma, personal fees from Eisai, personal fees from GW Pharmaceuticals, personal fees from Angelini Pharma, personal fees from Lusofarmaco, and personal fees from Ecupharma outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Epilepsy is a chronic neurological disorder affecting individuals globally, marked by recurrent and apparently unpredictable seizures that pose significant challenges, including increased mortality, injuries, and diminished quality of life. Despite advancements in treatments, a significant proportion of people with epilepsy continue to experience uncontrolled seizures. The apparent unpredictability of these events has been identified as a major concern for people with epilepsy, highlighting the need for innovative seizure forecasting technologies., Objective: The ATMOSPHERE study aimed to develop and evaluate a digital intervention, using wearable technology and data science, that provides real-time, individualized seizure forecasting for individuals living with epilepsy. This paper reports the protocol for one of the workstreams focusing on the design and testing of a prototype to capture real-time input data needed for predictive modeling. The first aim was to collaboratively design the prototype (work completed). The second aim is to conduct an "in-the-wild" study to assess usability and refine the prototype (planned research)., Methods: This study uses a person-based approach to design and test the usability of a prototype for real-time seizure precipitant data capture. Phase 1 (work completed) involved co-design with individuals living with epilepsy and health care professionals. Sessions explored users' requirements for the prototype, followed by iterative design of low-fidelity, static prototypes. Phase 2 (planned research) will be an "in-the-wild" usability study involving the deployment of a mid-fidelity, functional prototype for 4 weeks, with the collection of mixed methods usability data to assess the prototype's real-world application, feasibility, acceptability, and engagement. This phase involves primary participants (adults diagnosed with epilepsy) and, optionally, their nominated significant other. The usability study will run in 3 rounds of deployment and data collection, aiming to recruit 5 participants per round, with prototype refinement between rounds., Results: The phase-1 co-design study engaged 22 individuals, resulting in the development of a mid-fidelity, functional prototype based on identified requirements, including the tracking of evidence-based and personalized seizure precipitants. The upcoming phase-2 usability study is expected to provide insights into the prototype's real-world usability, identify areas for improvement, and refine the technology for future development. The estimated completion date of phase 2 is the last quarter of 2024., Conclusions: The ATMOSPHERE study aims to make a significant step forward in epilepsy management, focusing on the development of a user-centered, noninvasive wearable device for seizure forecasting. Through a collaborative design process and comprehensive usability testing, this research aims to address the critical need for predictive seizure forecasting technologies, offering a promising approach to improving the lives of individuals with epilepsy. By leveraging predictive analytics and personalized machine learning models, this technology seeks to offer a novel approach to managing epilepsy, potentially improving clinical outcomes, including quality of life, through increased predictability and seizure management., International Registered Report Identifier (irrid): DERR1-10.2196/60129., (©Emily E V Quilter, Samuel Downes, Mairi Therese Deighan, Liz Stuart, Rosie Charles, Phil Tittensor, Leandro Junges, Peter Kissack, Yasser Qureshi, Aravind Kumar Kamaraj, Amberly Brigden. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 19.09.2024.)

A new national treatment guideline from Danish Society of Anaesthesiology and Intensive Care Medicine (DASAIM) outlines the anaesthetic management of pre-eclampsia and eclampsia. Key principles involve blood pressure control, seizure treatment and prophylaxis, and restricted fluid therapy. Treatment algorithms, flow charts and checklists are provided. Anaesthetic recommendations for vaginal delivery and caesarean section are provided. Close monitoring, especially for patients with severe disease, organ dysfunction, or failure, is crucial, requiring a multidisciplinary approach, as argued in this review., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Rationale: The brain-computer interface (BCI) is core tasks in comprehensively understanding the brain, and is one of the most significant challenges in neuroscience. The development of novel non-invasive neuromodulation technique will drive major innovations and breakthroughs in the field of BCI. Methods: We develop a new noninvasive closed-loop acoustic brain-computer interface (aBCI) for decoding the seizure onset based on the electroencephalography and triggering ultrasound stimulation of the vagus nerve to terminate seizures. Firstly, we create the aBCI system and decode the onset of seizure via a multi-level threshold model based on the analysis of wireless-collected electroencephalogram (EEG) signals recorded from above the hippocampus. Then, the different acoustic parameters induced acoustic radiation force were used to stimulate the vagus nerve in a rat model of epilepsy-induced by pentylenetetrazole. Finally, the results of epileptic EEG signal triggering ultrasound stimulation of the vagus nerve to control seizures. In addition, the mechanism of aBCI control seizures were investigated by real-time quantitative polymerase chain reaction (RT-qPCR). Results: In a rat model of epilepsy, the aBCI system selectively actives mechanosensitive neurons in the nodose ganglion while suppressing neuronal excitability in the hippocampus and amygdala, and stops seizures rapidly upon ultrasound stimulation of the vagus nerve. Physical transection or chemical blockade of the vagus nerve pathway abolish the antiepileptic effects of aBCI. In addition, aBCI shows significant antiepileptic effects compared to conventional vagus nerve electrical stimulation in an acute experiment. Conclusions: Closed-loop aBCI provides a novel, safe and effective tool for on-demand stimulation to treat abnormal neuronal discharges, opening the door to next generation non-invasive BCI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: Although >30% of epilepsy patients have drug-resistant epilepsy (DRE), typically those with generalized or multifocal disease have not traditionally been considered surgical candidates. Responsive neurostimulation (RNS) of the centromedian (CM) region of the thalamus now appears to be a promising therapeutic option for this patient population. We present outcomes following CM RNS for 13 patients with idiopathic generalized epilepsy (IGE) and eight with multifocal onsets that rapidly generalize to bilateral tonic-clonic (focal to bilateral tonic-clonic [FBTC]) seizures., Methods: A retrospective review of all patients undergoing bilateral CM RNS by the senior author through July 2022 were reviewed. Electrodes were localized and volumes of tissue activation were modeled in Lead-DBS. Changes in patient seizure frequency were extracted from electronic medical records., Results: Twenty-one patients with DRE underwent bilateral CM RNS implantation. For 17 patients with at least 1 year of postimplantation follow-up, average seizure reduction from preoperative baseline was 82.6% (SD = 19.0%, median = 91.7%), with 18% of patients Engel class 1, 29% Engel class 2, 53% Engel class 3, and 0% Engel class 4. There was a trend for average seizure reduction to be greater for patients with nonlesional FBTC seizures than for other patients. For patients achieving at least Engel class 3 outcome, median time to worthwhile seizure reduction was 203.5 days (interquartile range = 110.5-343.75 days). Patients with IGE with myoclonic seizures had a significantly shorter time to worthwhile seizure reduction than other patients. The surgical targeting strategy evolved after the first four subjects to achieve greater anatomic accuracy., Significance: Patients with both primary and rapidly generalized epilepsy who underwent CM RNS experienced substantial seizure relief. Subsets of these patient populations may particularly benefit from CM RNS. The refinement of lead targeting, tuning of RNS system parameters, and patient selection are ongoing areas of investigation., (© 2024 International League Against Epilepsy.)

Background: Deep brain stimulation of the central thalamus (CT-DBS) has potential for modulating states of consciousness, but it can also trigger electrographic seizures, including poly-spike-wave trains (PSWT)., Objectives: To report the probability of inducing PSWTs during CT-DBS in awake, freely-moving mice., Methods: Mice were implanted with electrodes to deliver unilateral and bilateral CT-DBS at different frequencies while recording electroencephalogram (EEG). We titrated stimulation current by gradually increasing it at each frequency until a PSWT appeared. Subsequent stimulations to test arousal modulation were performed at the current one step below the current that caused a PSWT during titration., Results: In 2.21% of the test stimulations (10 out of 12 mice), CT-DBS caused PSWTs at currents lower than the titrated current, including currents as low as 20 μA., Conclusion: Our study found a small but significant probability of inducing PSWTs even after titration and at relatively low currents. EEG should be closely monitored for electrographic seizures when performing CT-DBS in both research and clinical settings., Competing Interests: Declaration of competing interest Emery N. Brown holds patents on anesthetic state monitoring and control; holds founding interest in PASCALL, a start-up developing physiological monitoring systems; receives royalties from intellectual property through Massachusetts General Hospital licensed to Masimo. The interests of Emery N. Brown were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. The rest of the authors do not have any interest to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Functional seizures (FS) account for 20%-25% of referrals to specialist epilepsy clinics. They are associated with major disability, increased mortality, and frequent and costly health care use. Current guidelines emphasize the importance of implementing clinical pathways to coordinate and deliver effective treatment, but there are few targeted evidence-based interventions that reliably improve patient outcomes, and treatment resources are limited. We conducted a retrospective evaluation of Re-PROGRAM, a novel, brief intervention for functional seizure patients, to assess its feasibility in an outpatient setting., Methods: Twenty-nine patients with FS undertook Re-PROGRAM between August 2020 and January 2022 at the Alfred Hospital Functional Seizures Clinic, Melbourne, Australia. The intervention comprised five 60-90-min consecutive weekly appointments via telehealth, where psychologists engaged patients in a structured program of seizure management skills, lifestyle modification, and behavioral activation strategies. Following the intervention, patient feedback was collected in routine clinical follow-up as well as with a 24-item self-report pre-/postintervention comparison questionnaire., Results: All 29 patients who enrolled in Re-PROGRAM completed the scheduled sessions. Of those who returned the postintervention questionnaire (n = 16), 15 reported a reduction in seizure frequency. Four patients were lost to follow-up. Of the remaining nine, eight reported seizure frequency reduction during clinical follow-up. Qualitative analysis of the feedback revealed the majority of patients reported reduced seizure duration, intensity, and bothersomeness, and patients felt improvements in their sense of control over seizures, confidence to use seizure control strategies, assertive communication, problem solving, coping skills, relationships with others, and their day-to-day functioning., Significance: This retrospective evaluation demonstrates the feasibility and acceptability of Re-PROGRAM as a brief intervention for individuals diagnosed with FS delivered in a clinical outpatient setting and warrants further investigation in larger scale, randomized controlled studies., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: With epilepsy increasingly affecting older adults, seizure-related care needs arise in new settings. Persons in these settings must receive optimal support and challenges identified for remediation. This may entail the epilepsy community researching in unfamiliar environments. One setting is care homes. Seizure-related ambulance incidents in them are common. We conducted the first qualitative study with care home staff to explore their experiences and challenges in managing suspected seizures., Methods: Three online focus groups were organised for January 2024 to explore ambulance calls, post-incident procedures, and challenges faced by care home staff when managing seizures. Persons were eligible to participate if they worked as a care assistant, nurse or manager in a care home in North-West England. Different recruitment pathways were employed including direct approach, a managers' network, social media and a register of research interested homes. Focus group audio recordings were transcribed and analysed using Hamilton's Rapid Analysis., Results: Recruitment was difficult; 13 care home staff from 12 different homes were ultimately recruited. Despite data saturation not being achieved, insights were gained regarding ambulance call decisions, paperwork navigation, and follow-up care challenges. Patients not having meaningful seizure action plans in place and regulatory restrictions were identified as factors that contributed to potentially avoidable calls for ambulance help being made., Conclusion: This study highlights systemic issues in care homes' seizure care, emphasizing the need for further research. The epilepsy community may need to innovate to better research within this increasingly important setting. This study offers insights into the effectiveness of different recruitment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ogden syndrome, also known as NAA10-related neurodevelopmental syndrome, is a rare genetic condition associated with pathogenic variants in the NAA10 N-terminal acetylation family of proteins. The condition was initially described in 2011 and is characterized by a range of neurologic symptoms, including intellectual disability and seizures, as well as developmental delays, psychiatric symptoms, congenital heart abnormalities, hypotonia, and others. Previously published articles have described the etiology and phenotype of Ogden syndrome, mostly with retrospective analyses; herein, we report prospective data concerning its progress over time. The current study involves a total of 58 distinct participants; of these, 43 caregivers were interviewed using the Vineland-3 and answered a survey regarding therapy and other questions, 10 of whom completed the Vineland-3 but did not answer the survey, and 5 participants who answered the survey but have not yet performed the Vineland-3 due to language constraints. The average age at the time of the most recent assessment was 12.4 years, with individuals ranging in age from 11 months to 40.2 years. Using Vineland-3 scores, we show decline in cognitive function over time in individuals with Ogden syndrome (n = 53). Sub-domain analysis found the decline to be present across all modalities. In addition, we describe the nature of seizures in this condition in greater detail, as well as investigate how already-available non-pharmaceutical therapies impact individuals with NAA10-related neurodevelopmental syndrome. Additional investigation between seizure and non-seizure groups showed no significant difference in adaptive behavior outcomes. A therapy investigation showed speech therapy to be the most commonly used therapy by individuals with NAA10-related neurodevelopmental syndrome, followed by occupational and physical therapy, with more severely affected individuals receiving more types of therapy than their less-severe counterparts. Early intervention analysis was only significantly effective for speech therapy, with analyses of all other therapies being non-significant. Our study portrays the decline in cognitive function over time of individuals within our cohort, independent of seizure status, and therapies being received, and highlights the urgent need for the development of effective treatments for Ogden syndrome., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Background: Epilepsy is a multifactorial neurological disorder, including parasitic infections of the brain such as neurocysticercosis (NCC). People with epileptic seizures (PWES) in low and middle-income countries often do not receive appropriate treatment, which besides epileptic seizures, may also lead to reduced quality of life and possibly death. The objective of this study was to describe gaps in treatment of epileptic seizures in a Zambian rural area., Methods: A cross-sectional study was conducted in Sinda district of Zambia between August and October 2018. PWES identified from clinic records and with the help of community healthcare workers were recruited. Two questionnaires, one to PWES and the other to local healthcare workers, were administered to describe the treatment gap., Results: A total of 146 PWES and 43 healthcare workers were interviewed. Of the 146 PWES, 131 had taken anti-seizure medication (ASM) at some point since their seizure onset, of which 49.6% were on current treatment. Only 18.3% were on continuous ASM, an overall treatment gap of 83.6%. Over 55% of healthcare workers did not know the relationship between epilepsy and NCC. The risk factors associated with lack of appropriate treatment were stock-outs of ASMs, lack of diagnostic equipment, poor patient follow-up, and PWES opting for traditional medicine., Conclusion: The treatment gap is substantial in Sinda district. The causes are multifactorial, involving shortcomings at the level of healthcare facilities, communities, and individuals. Directed training of healthcare workers and significant improvements in the supply and dispensing of ASMs will be key in substantially reducing the gap., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Objective: Deep brain stimulation (DBS) is a promising approach for the treatment of epilepsy. However, the optimal target for DBS and underlying mechanisms are still not clear. Here, we compared the therapeutic effects of DBS on distinct septal subregions, aimed to find the precise targets of septal DBS and related mechanisms for the clinical treatment., Methods: Assisted by behavioral test, electroencephalography (EEG) recording and analyzing, selectively neuronal manipulation and immunohistochemistry, we assessed the effects of DBS on the three septal subregions in kainic acid (KA)-induced mouse seizure model., Results: DBS in the medial septum (MS) not only delayed generalized seizure (GS) development, but reduced the severity; DBS in the vertical diagonal band of Broca (VDB) only reduced the severity of GS, while DBS in the horizontal diagonal band of Broca (HDB) subregion showed no anti-seizure effect. Notably, DBS in the MS much more efficiently decreased abnormal activation of hippocampal neurons. EEG spectrum analysis indicated that DBS in the MS and VDB subregions mainly increased the basal hippocampal low-frequency (delta and theta) rhythm. Furthermore, ablation of cholinergic neurons in the MS and VDB subregions blocked the anti-seizure and EEG-modulating effects of septal DBS, suggesting the seizure-alleviating effect of DBS was dependent on local cholinergic neurons., Significance: DBS in the MS and VDB, rather than HDB, attenuates hippocampal seizure by activation of cholinergic neurons-augmented hippocampal delta/theta rhythm. This may be of great therapeutic significance for the clinical treatment of epilepsy with septal DBS., Plain Language Summary: The optical target of deep brain stimulation in the septum is still not clear. This study demonstrated that stimulation in the medial septum and vertical diagonal band of Broca subregions, but not the horizontal diagonal band of Broca, could alleviate hippocampal seizure through cholinergic neurons-augmented hippocampal delta/theta rhythm. This study may shed light on the importance of precise regulation of deep brain stimulation therapy in treating epileptic seizures., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: The presented evidence-based clinical practice guideline (CPG) is proposed as a National CPG where we adapted the international recommendations for the emergency management of seizures in children beyond the neonatal period to suit the health care in Egypt. The quality of evidence and the strength of recommendations are indicated. This study aimed to standardize the treatment of acute epileptic seizures and to provide an easy-to-apply acute treatment protocol that will allow immediate and appropriate seizure control., Methods: This is part of a larger program by the Egyptian Pediatric Clinical Practice Guidelines Committee (EPG) in collaboration with the staff of pediatric departments of 15 Egyptian universities and the National Research Centre. EPG was affiliated later to the Supreme Council of the Egyptian University Hospitals aiming to define the topics of, assign authors to, and assist in the adaptation of pediatric evidence-based CPGs according to a national strategic plan (http://epg.edu.eg). The committee is guided by a formal CPG adaptation methodology: the "Adapted ADAPTE.", Results: The Egyptian Childhood Seizure Group (ECSG) reviewed the results of the Appraisal of Guidelines for Research and Evaluation II assessment and decided to adapt the recommendations of three source CPGs: American Epilepsy Society, Italian League Against Epilepsy, Neurocritical Care Society, and Neurologic & Psychiatric Society of Zambia. Eight implementation tools were included. A comprehensive set of multifaceted CPG implementation strategies was provided for the clinicians, patients, nurses, and other relevant stakeholders contextualized to the national settings., Conclusions: Our experience with this adaptation methodology provides useful insight into its national utilization in Egypt., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The management of prolonged seizures (PS) and seizure clusters (SC) is impeded by the lack of international, evidence-based guidance. We aimed to develop expert recommendations regarding consensus definitions of PS, SC, and treatment goals to prevent progression to higher-level emergencies such as status epilepticus (SE)., Methods: An expert working group, comprising 12 epileptologists, neurologists, and pharmacologists from Europe and North America, used a modified Delphi consensus methodology to develop and anonymously vote on statements. Consensus was defined as ≥75% voting "Agree"/"Strongly agree.", Results: All group members strongly agreed that termination of an ongoing seizure in as short a time as possible is the primary goal of rapid and early seizure termination (REST) and that an ideal medication for REST would start to act within 2 min of administration to terminate ongoing seizure activity. Consensus was reached on the terminology defining PS (with proposed thresholds of 5 min for prolonged focal seizures and 2 min for prolonged absence seizures and the convulsive phase of bilateral tonic-clonic seizures) and SC (an abnormal increase in seizure frequency compared with the individual patient's usual seizure pattern). All group members strongly agreed or agreed that patients who have experienced a PS should be offered a REST medication, and all patients who have experienced a SC should be offered an acute cluster treatment (ACT). Further, when prescribing a REST medication or ACT, a seizure action plan should be agreed upon in consultation with the patient and caregiver., Significance: The expert working group had a high level of agreement on the recommendations for defining and managing PS and SC. These recommendations will complement the existing guidance for the management of acute seizures, with the possibility of treating them earlier to potentially avoid progression to more severe seizures, including SE., (© 2024 The Author(s). Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Cognitive behavioural therapy (CBT) and other psychological approaches have a growing evidence base for treating Non-Epileptic Seizures (NES). However, communication about the diagnosis can be difficult for clinicians and is not always well received. It is thought that Psychoeducation about NES may improve engagement with treatment such as CBT and may contribute to reductions in the frequency of seizures and improvements in health related quality of life. However, psychoeducational components of treatment are often not evaluated in isolation meaning the specific benefit to patients is not currently well understood., Aims: The researchers aimed to examine the outcomes associated with psychoeducational interventions and the content of these programmes for NES., Method: A scoping review was undertaken across four databases with seventeen eligible studies identified which were charted to analyse the data., Results: Findings revealed that components and modalities of interventions varied as did methods of evaluating the interventions. A number of different outcome measures were used and not all studies reported the significance of findings. Results across studies were inconsistent; however, there was a general trend across the studies of symptom reduction and improvement in mental health., Conclusions: Findings illustrate that psychoeducation has potential benefits as an intervention in its own right. However, it may be best placed as a second step in a stepped care model, between initial diagnosis and further psychological treatment. The present literature needs replication and more robust studies for more certain conclusions to be drawn., Competing Interests: Declarations of competing interest We, the authors declare no conflicts of interests in submitting this article., (Copyright © 2024. Published by Elsevier Ltd.)

Previously known as Munchausen syndrome by proxy, medical child abuse is a form of child maltreatment whereby the caregiver creates an environment in which medical care harms or threatens the wellbeing of a child. Approximately 40-50 % of medical child abuse cases involve neurological symptoms, with fabricated or induced seizures accounting for a significant proportion. Identifying fictitious seizures is often difficult even for the most experienced clinicians. Therefore, having a low threshold for clinical suspicion is essential in the timely diagnosis of medical child abuse. This article provides a review of the epidemiology, diagnosis, and management of medical child abuse when it involves seizures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Importance: Electroconvulsive therapy (ECT), wherein a generalized epileptic seizure is induced, is a treatment for major depressive disorder (MDD). Currently, it is unclear whether there is an association between seizure length and treatment outcome., Objective: To explore the association between seizure duration, potential confounding variables, and ECT treatment outcome., Design, Setting, and Participants: This population-based cohort study obtained data from the Swedish National Quality Register for ECT. Patients treated for unipolar MDD with unilateral electrode placement between January 1, 2012, and December 31, 2019, were included. The electroencephalographic (EEG) seizure duration from the first ECT treatment session for each patient was used for analysis. Data analyses were performed between March 2021 and May 2024., Main Outcomes and Measures: The primary outcome was remission, defined as a cutoff score of less than 10 points on the self-assessment version of the Montgomery-Åsberg Depression Rating Scale within 1 week after ECT. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) between different seizure duration groups. Furthermore, the associations between concomitant use of pharmacological treatments, seizure duration, and remission rate were explored., Results: Among the 6998 patients included, 4229 (60.4%) were female and the mean (SD) age was 55.2 (18.6) years. Overall, 2749 patients (39.3%) achieved remission after ECT. Patients with EEG seizure duration of 60 to 69 seconds had the highest remission rates compared with patients with seizure duration of less than 20 seconds (OR, 2.17; 95% CI, 1.63-2.88; P < .001). Anticonvulsant medications were associated with shorter seizure duration (eg, lamotrigine: β coefficient [SE], -6.02 [1.08]; P < .001) and lower remission rates (eg, lamotrigine: adjusted OR, 0.67; 95% CI, 0.53-0.84; P < .001)., Conclusions and Relevance: This study found an association between seizure length and remission from MDD. Use of anticonvulsant medication during ECT was associated with shorter seizure duration and lower remission rates after ECT.

Objectives: A seizure action plan (SAP) is a powerful tool that provides actionable information for caregivers during seizures. Guidelines have expressed the need for individualized SAPs. Our quality improvement team aimed to increase implementation of an SAP within a pediatric tertiary center, initially among epilepsy providers and expanded to all neurology providers., Methods: Process changes were implemented using Plan-Do-Study-Act cycles and data were evaluated monthly using control charts. The team focused on tracking patients who received SAPs and identified opportunities for improvement, including reminders within the electronic medical record, and standardizing clinic processes. A secondary analysis was performed to trend emergency department (ED) use among our patient population., Results: The SAP utilization rate among epilepsy providers increased from a baseline of 39% to 78% by December 2019 and reached the goal of 85% by June 2020, with a further increase to 92% by February 2022 and maintained. The SAP utilization rate among general neurology providers increased from 43% in 2018 to 85% by July 2020, and further increased to 93% by February 2022 and maintained. ED visits of established patients with epilepsy decreased from a baseline of 10.2 per 1000 to 7.5 per 1000., Conclusions: Quality improvement methodologies increased the utilization of a standardized SAP within neurology outpatient care centers. The SAP is a simplified tool that allows patients and providers to navigate a complex health care system. The utility of an SAP may potentially extend to minimizing unnecessary ED visits., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Research has demonstrated that implementation of Nocebo Hypothesis Cognitive Behavioural Therapy (NH-CBT) achieved full symptom remission in 93% of people with Functional Neurological Symptoms Disorder (FNSD), most of them exhibiting motor symptoms. The basis for NH-CBT is consistent with a predictive coding aetiological model of FNSD. This idea is transparently shared with people with FNSD in the form of telling them that their symptoms are caused by a nocebo effect, usually followed by some physical activity that aims to change the person's belief about their body., Aims: To demonstrate that a version of NH-CBT can also be effective in eliminating or reducing non-epileptic seizures (assumed to be a sub-type of FNSD)., Method: A consecutive case series design was employed. Participants were treated with NH-CBT over a 12-week period. The primary outcome measure was seizure frequency. Numerous secondary measures were employed, as well as a brief qualitative interview to explore participants' subjective experience of treatment., Results: Seven out of the 10 participants became seizure free at least 2 weeks before their post-treatment assessment, and all stayed seizure-free for at least 5 months. Six of those seven remained seizure free at 6-month follow-up. There were large positive effect sizes for the majority of secondary measures assessed., Conclusions: This case series provides evidence of feasibility and likely utility of NH-CBT in reducing the frequency of non-epileptic seizures.

Background and Purpose: Primary mitochondrial diseases (PMDs) are common inborn errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders typically affect tissues with high energy requirements, including heart, muscle and brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and often represents a poor prognostic feature. The aim of this study was to develop guidelines and consensus recommendations on safe medication use and seizure management in mitochondrial epilepsy., Methods: A panel of 24 experts in mitochondrial medicine, pharmacology and epilepsy management of adults and/or children and two patient representatives from seven countries was established. Experts were members of five different European Reference Networks, known as the Mito InterERN Working Group. A Delphi technique was used to allow the panellists to consider draft recommendations on safe medication use and seizure management in mitochondrial epilepsy, using two rounds with predetermined levels of agreement., Results: A high level of consensus was reached regarding the safety of 14 out of all 25 drugs reviewed, resulting in endorsement of National Institute for Health and Care Excellence guidelines for seizure management, with some modifications. Exceptions including valproic acid in POLG disease, vigabatrin in patients with γ-aminobutyric acid transaminase deficiency and topiramate in patients at risk for renal tubular acidosis were highlighted., Conclusions: These consensus recommendations describe our intent to improve seizure control and reduce the risk of drug-related adverse events in individuals living with PMD-related epilepsy., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Psychological interventions are the most recommended treatment for functional/dissociative seizures (FDS); however, there is ongoing uncertainty about their effectiveness on seizure outcomes., Methods: This systematic review and meta-analysis synthesises the available data. In February 2023, we completed a systematic search of four electronic databases. We described the range of seizure-related outcomes captured, used meta-analytic methods to analyse data collected during treatment and follow-up; and explored sources of heterogeneity between outcomes., Results: Overall, 44 relevant studies were identified involving 1,300 patients. Most were categorised as being at high (39.5 %) or medium (41.9 %) risk of bias. Seizure frequency was examined in all but one study; seizure intensity, severity or bothersomeness in ten; and seizure duration and cluster in one study each. Meta-analyses could be performed on seizure freedom and seizure reduction. A pooled estimate for seizure freedom at the end of treatment was 40 %, while for follow-up it was 36 %. Pooled rates for ≥50 % improvement in seizure frequency were 66 % and 75 %. None of the included moderator variables for seizure freedom were significant. At the group level, seizure frequency improved during the treatment phase with a moderate pooled effect size (d = 0.53). FDS frequency reduced by a median of 6.5 seizures per month. There was also evidence of improvement of the other (non-frequency) seizure-related measures with psychological therapy, but data were insufficient for meta-analysis., Conclusions: The findings of this study complement a previous meta-analysis describing psychological treatment-associated improvements in non-seizure-related outcomes. Further research on the most appropriate FDS-severity measure is needed., Competing Interests: Declaration of competing interest Dr. Kerr writes paid review articles on this topic for Medlink Neurology; is a paid consultant for SK Life Sciences, Biohaven Pharmaceuticals (Data Management Committee), Cerebral Therapeutics (Scientific Advisory Board), EpiTel; and has collaborative or data use agreements with Eisai, Janssen, Johnson & Johnson, Radius Health, UCB, GlaxoSmithKline, and Jazz Pharmaceuticals. These companies had no part in the current work. We affirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with these guidelines., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)