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Item Implementation of an evidence-based seizure algorithm in intellectual disability nursing: A pilot study(2016) Auberry, Kathy; Cullen, DeborahBased on the results of the Surrogate Decision-Making Self Efficacy Scale (Lopez, 2009), this study sought to determine if nurses working in the field of intellectual disability experience increased confidence when they implemented the “American Association of Neuroscience Nurses Seizure Algorithm” during telephone triage. The results of the study indicated using the AANN Seizure Algorithm increased self-confidence for many of the nurses in guiding care decisions during telephone triage. The treatment effect was statistically significant -3.169, p, .01 for a small sample of study participants. This increase in confidence is clinically essential for two reasons. Many individuals with intellectual disability and epilepsy reside within community based settings. Intellectual disability nurses provide seizure guidance to this population living in community based settings via telephone triage. Nurses improved confidence is clinically essential and has implications for practice. Evidenced-based training tools provide a valuable mechanism by guiding nurses via best practices. Nurses may need to be formally trained for seizure management due to high epilepsy rates in this population.Item Recommendations for the design of therapeutic trials for neonatal seizures(Springer Nature, 2019-06) Soul, Janet S.; Pressler, Ronit; Allen, Marilee; Boylan, Geraldine; Rabe, Heike; Portman, Ron; Hardy, Pollyanna; Zohar, Sarah; Romero, Klaus; Tseng, Brian; Bhatt-Mehta, Varsha; Hahn, Cecil; Denne, Scott; Auvin, Stephane; Vinks, Alexander; Lantos, John; Marlow, Neil; Davis, Jonathan M.; Pediatrics, School of MedicineAlthough seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population.Item Seizures as an early symptom of autosomal dominant Alzheimer's disease(Elsevier, 2019-04) Vöglein, Jonathan; Noachtar, Soheyl; McDade, Eric; Quaid, Kimberly A.; Salloway, Stephen; Ghetti, Bernardino; Noble, James; Berman, Sarah; Chhatwal, Jasmeer; Mori, Hiroshi; Fox, Nick; Allegri, Ricardo; Masters, Colin L.; Buckles, Virginia; Ringman, John M.; Rossor, Martin; Schofield, Peter R.; Sperling, Reisa; Jucker, Mathias; Laske, Christoph; Paumier, Katrina; Morris, John C.; Bateman, Randall J.; Levin, Johannes; Danek, Adrian; Medical and Molecular Genetics, School of MedicineOur objective was to assess the reported history of seizures in cognitively asymptomatic mutation carriers for autosomal dominant Alzheimer's disease (ADAD) and the predictive value of seizures for mutation carrier status in cognitively asymptomatic first-degree relatives of ADAD patients. Seizure occurrence in the Dominantly Inherited Alzheimer Network observational study was correlated with mutation carrier status in cognitively asymptomatic subjects. Of 276 cognitively asymptomatic individuals, 11 (4%) had experienced seizures, and nine of these carried an ADAD mutation. Thus, in the Dominantly Inherited Alzheimer Network population, seizure frequency in mutation carriers was significantly higher than in noncarriers (p = 0.04), and the positive predictive value of seizures for the presence of a pathogenic mutation was 81.8%. Among cognitively asymptomatic ADAD family members, the occurrence of seizures increases the a priori risk of 50% mutation-positive status to about 80%. This finding suggests that ADAD mutations increase the risk of seizures.Item The Role of β4 Subunit in Epilepsy Susceptibility(2024-08) Fahim, Ahmed; Cummins, Theodore; Berbari, Nicolas F.; Mastracci, TeresaSeizure involves a sudden, uncontrolled electrical disturbance of the brain due to many different causes apart from epilepsy, for example, high fever, low level of blood sugar, alcohol withdrawal, and many more, including the infections in the brain. In fact, epilepsy is a group of chronic neurological disorders characterized by recurrent unprovoked sudden-onset seizures. It stands as one of the prevalent brain disorders globally, impacting over 70 million individuals. The origins of epilepsy are multifaceted, coming from a mix of genetic and environmental factors including genetic predispositions, brain-related conditions (like tumors or strokes), infectious diseases, and traumatic brain injuries. Seizures can be partly referred to the dysregulation of ion channels, including voltage-gated sodium channels which will impact the action potential (electrical impulses that are responsible for the communication that takes place between neurons in the brain). These voltage-gated sodium channels mediate the depolarization responsible for the generation and conduction of action potentials. They are crucial in the generation and continuous electrical signals of the tissues that respond rapidly, like the neurons, and thus forming part of their function. In epilepsy, therefore, it is relevant to that domain in which abnormal functions of these sodium channels come up. Any change or dysfunction of these channels affect the excitability of the neurons themselves, with the consequence that an increased probability occurs in which abnormal electrical activity can be generated, hence the convulsions. Voltage-gated sodium channels are made up of large transmembrane proteins, having a single alpha subunit and related beta subunits. The beta subunit is an auxiliary protein that modulates channel gating, kinetics, surface expression, and the unique resurgent current, thereby influencing neuronal excitability and signaling. Resurgent currents represent a kind of current that can develop during action potential repolarization. They are characterized by a resurgent sodium current, the current which follows the initial sodium inflow in depolarization. Resurgent sodium currents are characterized by a rebound increase in sodium current during the repolarization phase of the action potential. Unlike the classic transient sodium current that inactivates rapidly upon membrane depolarization, the resurgent current is facilitated by the partial block and unblock of the sodium channel pore by the β subunit or other intracellular molecules during the repolarization phase. This allows sodium ions to flow into the cell when this blockage removed before it goes to closed state. It is believed widely to be of keen importance in neuronal excitability. The role of resurgent currents in epilepsy is likely genetically influenced with some environmental influence. Genetic mutations and dysregulation of the gene code for voltage-gated sodium channels, especially those related to beta subunits, can be linked to some atypical resurgent current. This increases the chance of having a seizure, which could develop into epilepsy. Four beta subunits have been identified up to now. As such, my investigation will focus on the beta 4 subunit and its possible involvement in increased susceptibility to seizures. My study will involve a genetically modified mouse β4 knockout (K.O) of the voltage-gated sodium channel, which will be compared with a wild type (WT) mouse model. To facilitate this comparison, I will prepare cortical brain slices from both the genetically modified and WT mice using a (Leica VT1200s vibratome). These slices will then be analyzed with multi-electrode arrays to detect electrical activity and measure the neurons' electrical responses. Additionally, I use 4-Aminopyridine, a potassium channel blocker, to stimulate electrical activity in the neurons and brain slices. Using the methodology outlined above, I aimed to investigate the ability to induce and measure neuronal activity in the β4 K.O mouse model. This involved comparing the neuronal activity between the β4 K.O and WT mice in terms of frequency and amplitude. The analysis of the recorded data was performed using Spike2 software, in conjunction with the multi-electrode array recordings. Furthermore, I explored whether variations in temperature (body temp vs 40℃) affect neuronal activity differently in β4 K.O compared to WT mice. In conclusion, my observations revealed that neuronal activity could indeed be induced in the β4 K.O mice, with a noted decrease in the frequency of this activity compared to WT mice, but an increase in amplitude. These outcomes were consistent at both normal body temperature and at an elevated temperature of 40°C, as analyzed using Spike2 software. However, when conducting a statistical analysis using a two-way ANOVA to compare between the β4 K.O and WT mice, and between body temperature and 40°C conditions, no significant differences were observed. Despite this, it is a general observation and conclusion that β4 K.O mice exhibit altered neuronal activity compared to WT mice. To gain a deeper understanding of the role of the β4 subunit on the alpha subunit of the voltage-gated sodium channel, adopting alternative methods such as patch clamp techniques or in vivo studies with intracranial electrodes may be beneficial. This suggestion comes considering various challenges and limitations encountered during my study, such as maintaining the viability of the slices for extended periods and minimizing noise in multi-electrode array (MEA) recordings. Mutations of β-subunit-encoding genes have been associated with such a wide array of debilitating diseases that include epilepsy, cancer, neuropathic pain, and febrile seizures, to some of the most prevalent conditions in neurodegeneration. Further study will be needed to better understand the biology of these important proteins and their potential for use as new targets for several disease states. Even so, the role of β4 remains somewhat controversial.