Scoping review of disease-modifying effect of drugs in experimental epilepsy.

Objective: Epilepsy affects ~50 million people worldwide causing significant medical, financial, and sociologic concerns for affected patients and their families. To date, treatment of epilepsy is primarily symptomatic management because few effective preventative or disease-modifying interventions exist. However, recent research has identified neurobiological mechanisms of epileptogenesis, providing new pharmacologic targets to investigate. The current scientific evidence remains scattered across multiple studies using different model and experimental designs. The review compiles different models of anti-epileptogenic investigation and highlights specific compounds with potential epileptogenesis-modifying experimental drugs. It provides a platform for standardization of future epilepsy research to allow a more robust compound analysis of compounds with potential for epilepsy prevention. Methods: PubMed, Ovid MEDLINE, and Web of Science were searched from 2007 to 2021. Studies with murine models of epileptogenesis and explicitly detailed experimental procedures were included in the scoping review. In total, 51 articles were selected from 14,983 and then grouped by five core variables: (1) seizure frequency, (2) seizure severity, (3) spontaneous recurrent seizures (SRS), (4) seizure duration, and (5) mossy fiber sprouting (MFS). The variables were differentiated based on experimental models including methods of seizure induction, treatment schedule and timeline of data collection. Data was categorized by the five core variables and analyzed by converting original treatment values to units of percent of its respective control. Results: Discrepancies in current epileptogenesis models significantly complicate inter-study comparison of potential anti-epileptogenic interventions. With our analysis, many compounds showed a potential to reduce epileptogenic characteristics defined by the five core variables. WIN55,212-2, aspirin, rapamycin, 1400W, and LEV + BQ788 were identified compounds with the potential of effective anti-epileptic properties. Significance: Our review highlights the need for consistent methodology in epilepsy research and provides a novel approach for future research. Inconsistent experimental designs hinder study comparison, slowing the progression of treatments for epilepsy. If the research community can optimize and standardize parameters such as methods of seizure induction, administration schedule, sampling time, and aniMal models, more robust meta-analysis and collaborative research would follow. Additionally, some compounds such as rapamycin, WIN 55,212-2, aspirin, 1400W, and LEV + BQ788 showed anti-epileptogenic modulation across multiple variables. We believe they warrant further study both individually and synergistically.

Brain injuries can set up an epileptogenic neuronal network.

Development of epilepsy or epileptogenesis promotes recurrent seizures. As of today, there are no effective prophylactic therapies to prevent the onset of epilepsy. Contributing to this deficiency of preventive therapy is the lack of clarity in fundamental neurobiological mechanisms underlying epileptogenesis and lack of reliable biomarkers to identify patients at risk for developing epilepsy. This limits the development of prophylactic therapies in epilepsy. Here, neural network dysfunctions reflected by oscillopathies and microepileptiform activities, including neuronal hyperexcitability and hypersynchrony, drawn from both clinical and experimental epilepsy models, have been reviewed. This review suggests that epileptogenesis reflects a progressive and dynamic dysfunction of specific neuronal networks which recruit further interconnected groups of neurons, with this resultant pathological network mediating seizure occurrence, recurrence, and progression. In the future, combining spatial and temporal resolution of neuronal non-invasive recordings from patients at risk of developing epilepsy, together with analytics and computational tools, may contribute to determining whether the brain is undergoing epileptogenesis in asymptomatic patients following brain injury.

HIV post-exposure prophylaxis in the emergency department: An updated assessment and opportunities for HIV prevention identified.

OBJECTIVES: Research suggests nonoccupational post exposure prophylaxis (nPEP) is under prescribed for people seeking treatment within 72 h of human immunodeficiency virus (HIV) exposures in the emergency department (ED). This study is an assessment of ED prescribers' knowledge, attitudes and practices regarding administration of HIV nPEP. METHODS: This was an anonymous survey based on literature review and modified Delphi technique. We approached 153 ED participants at work over a 4-month period from 5 hospital-based and 2 freestanding EDs. There were 152 completed surveys: 80 attendings, 27 residents, and 44 physician assistants. RESULTS: The majority of those surveyed (133/149, 89.3%) believe it is their responsibility to provide HIV nPEP in the ED. Although 91% (138/151) and 87% (132/151) of participants are willing to prescribe nPEP for IV drug use and unprotected sex, respectively, only 40% (61/152) of participants felt they could confidently prescribe the appropriate regimen. Only 25% (37/151) of participants prescribed nPEP in the last year. Participants considered time (27%), connecting patients to follow-up (26%), and cost to patients (23%), as barriers to prescribing nPEP. CONCLUSIONS: This study identified perceived barriers to administration of nPEP and missed opportunities for HIV prevention in the ED. Although most ED prescribers were willing to prescribe nPEP and felt it is their responsibility to do so, the majority of prescribers were not confident in prescribing it. The most commonly cited barriers to prescribing nPEP were time and access to follow-up care.