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INTRODUCTION: Although prompt treatment of status epilepticus is standard of care, the effect of timing of rescue therapy administration for seizure clusters in epilepsy remains unknown. Seizure clusters are a rare but clinically important condition, and benzodiazepines are the cornerstone rescue therapy for seizure clusters in epilepsy. We characterized temporal patterns from a large dataset of treated seizure clusters in the safety study of diazepam nasal spray. METHODS: This post hoc analysis used timing data of treated seizure clusters recorded by care partners and patients in seizure diaries during a 1-year safety study. Data analysis used time from seizure start to administration of diazepam. RESULTS: From 4466 observations, 3225 had data meeting criteria for analysis. Overall, median times from seizure start to dose administration, dose administration to seizure termination, and total seizure duration were 2, 3, and 7 min, respectively. In seizure clusters treated in

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia.

ObjectiveDespite the overall success of responsive neurostimulation (RNS) therapy for drug-resistant focal epilepsy, clinical outcomes in individuals vary significantly and are hard to predict. Biomarkers that indicate the clinical efficacy of RNS-ideally before device implantation-are critically needed, but challenges include the intrinsic heterogeneity of the RNS patient population and variability in clinical management across epilepsy centers. The aim of this study is to use a multicenter dataset to evaluate a candidate biomarker from intracranial electroencephalographic (iEEG) recordings that predicts clinical outcome with subsequent RNS therapy.MethodsWe assembled a federated dataset of iEEG recordings, collected prior to RNS implantation, from a retrospective cohort of 30 patients across three major epilepsy centers. Using ictal iEEG recordings, each center independently calculated network synchronizability, a candidate biomarker indicating the susceptibility of epileptic brain networks to RNS therapy.ResultsIctal measures of synchronizability in the high-γ band (95-105 Hz) significantly distinguish between good and poor RNS responders after at least 3 years of therapy under the current RNS therapy guidelines (area under the curve = .83). Additionally, ictal high-γ synchronizability is inversely associated with the degree of therapeutic response.SignificanceThis study provides a proof-of-concept roadmap for collaborative biomarker evaluation in federated data, where practical considerations impede full data sharing across centers. Our results suggest that network synchronizability can help predict therapeutic response to RNS therapy. With further validation, this biomarker could facilitate patient selection and help avert a costly, invasive intervention in patients who are unlikely to benefit.

Genetic mutations to the Lamin A/C gene (LMNA) can cause heart disease, but the mechanisms making cardiac tissues uniquely vulnerable to the mutations remain largely unknown. Further, patients with LMNA mutations have highly variable presentation of heart disease progression and type. In vitro patient-specific experiments could provide a powerful platform for studying this phenomenon, but the use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) introduces heterogeneity in maturity and function thus complicating the interpretation of the results of any single experiment. We hypothesized that integrating single cell RNA sequencing (scRNA-seq) with analysis of the tissue architecture and contractile function would elucidate some of the probable mechanisms. To test this, we investigated five iPSC-CM lines, three controls and two patients with a (c.357-2A>G) mutation. The patient iPSC-CM tissues had significantly weaker stress generation potential than control iPSC-CM tissues demonstrating the viability of our in vitro approach. Through scRNA-seq, differentially expressed genes between control and patient lines were identified. Some of these genes, linked to quantitative structural and functional changes, were cardiac specific, explaining the targeted nature of the disease progression seen in patients. The results of this work demonstrate the utility of combining in vitro tools in exploring heart disease mechanics.

ObjectiveTo explore the perspectives of adult patients with epilepsy, caregivers, and health care professionals (HCPs) on treatment for seizures and treatment decisions, we developed and administered the STEP Survey (Seize the Truth of Epilepsy Perceptions).MethodsParticipants were recruited from online panel M3 and by Rare Patient Voice and completed the self-administered online STEP Survey. Analysis of variance and chi-square tests were used for group comparisons.ResultsThe STEP Survey was completed by 400 adult patients, 201 caregivers, and 258 HCPs. Patients estimated reporting 45% of their seizures to their HCP, whereas caregivers estimated 83% and HCPs estimated 73% were reported. The most common reason for not reporting seizures was that the seizures were not serious enough to mention (patients 57%; caregivers 66%). A minority of patients (25%) and caregivers (30%) were very or extremely likely to ask their HCP about changing antiseizure medication (ASM) in the next 12 months. The HCP was most frequently selected by patients, caregivers, and HCPs as the person who initiates discussion of changing ASMs (patients 73%/caregivers 66%/HCPs 75%) and increasing ASM dosage (patients 77%/caregivers 68%/HCPs 81%). A majority of patients (65%) and caregivers (68%) somewhat or strongly agreed that they do not change ASMs due to fear of getting worse. HCPs perceive this fear less often, stating that 50% of their patients feel afraid when a second ASM was added.ConclusionsImproved reporting of all seizures, discussion of treatment changes, and the impact of fear on treatment decisions provide opportunities to reduce complacency and optimize patient outcomes.

Some patients with epilepsy continue to have seizures despite daily treatment with antiseizure medications. This includes seizure clusters (also known as acute repetitive seizures), which are an increase in seizure frequency that is different from the usual seizure pattern for that patient. In the literature, the term "rescue" is used for pharmacologic treatment for seizure clusters, but clarity regarding timing or whether a caregiver or patient should wait until a moment of life-threatening urgency before administering the medication is lacking. Additionally, the concept of waiting 5 minutes to identify and initiate treatment of status epilepticus has been carried over to the treatment of seizure clusters, as well as the idea of waiting owing to safety concerns, without reevaluation in the context of the reported safety profiles for currently available as-needed therapies when administered as prescribed. Delaying treatment of seizure clusters may have negative outcomes, including injury, emergency room use, hospitalization, and progression to status epilepticus. Additionally, increased time for administration of benzodiazepines, the cornerstone therapies for seizure clusters, may lower the potency and effectiveness once administration takes place, because of physiologic changes. Thus, clarifying the importance of timing in the treatment terminology may be of benefit in the acute context. The term "immediate-use seizure medication" (ISM), meaning treatment that is administered as quickly as possible once a seizure cluster is recognized, may help to clarify the timing of as-needed treatment. This review examines the recognition and definitions of seizure clusters, the physiologic rationale for ISM for seizure clusters, and the effectiveness and safety of early treatment. Remaining knowledge gaps are also discussed. The findings of this review suggest that it may be time to revisit the terminology of "rescue", which implies waiting to administer treatment for seizure clusters, as doing so is not supported by pathophysiologic, effectiveness, or safety data. Plain Language Summary: Some people with epilepsy have seizures even if they take daily medication for their seizures. If they have more seizures than usual in a day, this may be called a seizure cluster. Drugs used to treat clusters are often said to be "rescue" medicines. But the word "rescue" may imply that the medication should only be administered when serious danger is present. Additionally, possibly because of previous instructions, people may think they have to wait to see if the seizure lasts more than 5 minutes to give the medicine, or they may be concerned about how safe the medicine will be if they give it. This older approach needs to be revisited and replaced. Waiting to give medicine could make it more likely that a person could get hurt or require a hospital or emergency room visit or their seizure condition could worsen. Waiting also may allow for changes in the body that may make a medicine less effective once it is given. Because of this, it may be better to say these medicines are for "immediate use" rather than for "rescue". That way, the people giving the medicine know that they should give it as soon as they see the patient needs it. This paper discusses how seizure clusters are described and what can happen if someone waits to give medicine versus giving it right away. The paper shows that waiting may not be needed. [ABSTRACT FROM AUTHOR]

Science relies on increasingly complex data sets for progress, but common data management methods such as spreadsheet programs are inadequate for the growing scale and complexity of this information. While database management systems have the potential to rectify these issues, they are not commonly utilized outside of business and informatics fields. Yet, many research labs already generate "medium sized", low velocity, multi-dimensional data that could greatly benefit from implementing similar systems. In this article, we provide a conceptual overview explaining how databases function and the advantages they provide in tissue engineering applications. Structural fibroblast data from individuals with a lamin A/C mutation was used to illustrate examples within a specific experimental context. Examples include visualizing multidimensional data, linking tables in a relational database structure, mapping a semi-automated data pipeline to convert raw data into structured formats, and explaining the underlying syntax of a query. Outcomes from analyzing the data were used to create plots of various arrangements and significance was demonstrated in cell organization in aligned environments between the positive control of Hutchinson-Gilford progeria, a well-known laminopathy, and all other experimental groups. In comparison to spreadsheets, database methods were enormously time efficient, simple to use once set up, allowed for immediate access of original file locations, and increased data rigor. In response to the National Institutes of Health (NIH) emphasis on experimental rigor, it is likely that many scientific fields will eventually adopt databases as common practice due to their strong capability to effectively organize complex data.

Smartphones have become synonymous with modern living, providing users with countless apps to perform endless functions. Harnessing mobile technology to help caregivers of Alzheimer's Disease patients offers users tools and resources to engage, organize and lessen the stress of caregiving. Medical Librarians, healthcare professionals, family and friends can all benefit from learning about four popular Alzheimer's Disease caregiver apps to enable them to provide thoughtful recommendations to implement their use in caregivers' daily lives. [ABSTRACT FROM AUTHOR]

Wearables like the Apple Watch, Fitbit Charge 6, Garmin vivoactive 4S, and the Samsung Galaxy Sport are popular devices that tell time, monitor sleep, count calories, and track steps. These devices are increasingly expanding their features to include a more specialized focus on fitness goals, health monitoring and management, and promoting physical activity in various ways. The question is: What is their impact on increasing physical activity? Comparing the features and costs of the most popular wearables helps determine whether users should invest in these devices. [ABSTRACT FROM AUTHOR]

The letter discusses a retrospective case series on the use of assisted reproductive technology (ART) in women with epilepsy (PWE) who desire pregnancy. The study found that seizure control can be maintained despite the use of exogenous hormones. The authors emphasize the need for interdisciplinary collaboration and further research to optimize care for PWE undergoing ART. They also provide a table outlining considerations for epilepsy during different stages of in vitro fertilization (IVF) protocols. [Extracted from the article]

Cognitive Outcomes at Age 3 Years in Children With Fetal Exposure to Antiseizure Medications (MONEAD Study) in the USA: A Prospective, Observational Cohort Study Meador KJ, Cohen MJ, Loring DW, Matthews AG, Brown C, Robalino CP, Birnbaum AK, Voinescu PE, Kalayjian LA, Gerard EE, Gedzelman ER, Hanna J, Cavitt J, Sam M, French JA, Hwang S, Pack AM, Pennell PB; MONEAD Investigator Group. Lancet Neurol. 2023;22(8):712-722. doi:10.1016/S1474-4422(23)00199-0 Background: The neurodevelopmental effects of fetal exposure to most antiseizure medications are unclear. We aimed to investigate the effects of fetal exposure to commonly used antiseizure medications on neuropsychological outcomes at age 3 years. Methods: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicenter cohort study at 20 specialty epilepsy centers in the USA. We have investigated pregnancy outcomes in women (aged 14-45 years) with and without epilepsy who were enrolled during pregnancy (≤20 weeks' gestational age), and their children. The primary outcome for children at age 3 years was a blindly assessed Verbal Index score, which was calculated by averaging scores on the Naming Vocabulary and Verbal Comprehension subtests of Differential Ability Scales-II, Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale-5, and Peabody Picture Vocabulary Test-4. Children of women with and without epilepsy were compared, and the associations of medication exposures to outcomes in exposed children were assessed. The MONEAD study is registered with ClinicalTrials.gov, NCT0730170, and is ongoing. Findings: Between Dec 19, 2012, and Jan 13, 2016, 456 pregnant women (351 with epilepsy and 105 without epilepsy) were enrolled into the study. 345 children were born to women with epilepsy and 106 children were born to women without epilepsy. Verbal Index scores at age 3 years did not differ for children of women with epilepsy (n = 284; adjusted least-square mean 102.7, 95% CI 101.4 to 103.9) versus those without epilepsy (n = 87; 102.3, 99.8 to 104.7). Significant risk factors for reduced Verbal Index scores included maternal intelligence quotient, maternal education, post-birth anxiety, gestational age at enrolment, child's sex, and child's ethnicity. For Verbal Index scores, antiseizure medication exposure effects were not seen for maximum third trimester blood concentrations (n = 258; adjusted parameter estimate −2.9, 95% CI −6.7 to 1·0). However, in secondary analyses, exposure-dependent effects were present on multiple cognitive measures, which varied by medication. Interpretation: We found no difference in neurodevelopmental outcomes between children with fetal exposure to newer antiseizure medications compared with unexposed children. However, some exposure-dependent antiseizure medication effects were seen in secondary analyses. The adverse effects of maternal post-birth anxiety emphasize the importance of screening mothers during pregnancy and postpartum and implementing interventions. Additional studies are needed to clarify the exposure-dependent effects. [ABSTRACT FROM AUTHOR]