-
Medical Science Monitor : International... Oct 2023Eclampsia seizure is an always serious and potentially fatal obstetric condition. Safe delivery in women with pregnancies complicated by eclampsia seizures is still one... (Review)
Review
Eclampsia seizure is an always serious and potentially fatal obstetric condition. Safe delivery in women with pregnancies complicated by eclampsia seizures is still one of the greatest challenges in perinatal medicine. Pregnancy should be terminated (childbirth) in the safest and least traumatic way possible. Attempting vaginal delivery can take place only exceptionally, in the event of possibly quick completion of childbirth with a stable state of the mother and the fetus. However, immediate labor via cesarean section is most often recommended. It is essential to maintain left lateral patient positioning during cesarean section. Regional anesthesia can be used only in conscious patients who are free from coagulopathy and from HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome to decrease the risk of aspiration and failed intubation attempts in preeclamptic or eclamptic women. For sudden, unexpected interventions, when a patient arrives at the hospital with an eclampsia seizure without lab results, general anesthesia can be the best option and should be performed by an experienced medical team of anesthesiologists, ready to perform difficult intubation. Magnesium sulfate is the drug that should be used first to stop eclamptic convulsions and prevent their recurrence. Intravenous antihypertensive drugs can stabilize elevated blood pressure (BP), preventing multiorgan failure and recurrent eclampsia seizure, and thus the prevention of maternal death. This article aims to review the management of seizures during pregnancy in women with eclampsia to ensure safe delivery.
Topics: Female; Humans; Pregnancy; Cesarean Section; Eclampsia; HELLP Syndrome; Pre-Eclampsia; Seizures
PubMed: 37803822
DOI: 10.12659/MSM.941709 -
CNS Drugs Sep 2023γ-Aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter in the mammalian brain and has been found to play an important role in the pathogenesis or... (Review)
Review
New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: I. Role of GABA as a Modulator of Seizure Activity and Recently Approved Medications Acting on the GABA System.
γ-Aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter in the mammalian brain and has been found to play an important role in the pathogenesis or the expression of many neurological diseases, including epilepsy. Although GABA can act on different receptor subtypes, the component of the GABA system that is most critical to modulation of seizure activity is the GABA-receptor-chloride (Cl) channel complex, which controls the movement of Cl ions across the neuronal membrane. In the mature brain, binding of GABA to GABA receptors evokes a hyperpolarising (anticonvulsant) response, which is mediated by influx of Cl into the cell driven by its concentration gradient between extracellular and intracellular fluid. However, in the immature brain and under certain pathological conditions, GABA can exert a paradoxical depolarising (proconvulsant) effect as a result of an efflux of chloride from high intracellular to lower extracellular Cl levels. Extensive preclinical and clinical evidence indicates that alterations in GABAergic inhibition caused by drugs, toxins, gene defects or other disease states (including seizures themselves) play a causative or contributing role in facilitating or maintaning seizure activity. Conversely, enhancement of GABAergic transmission through pharmacological modulation of the GABA system is a major mechanism by which different antiseizure medications exert their therapeutic effect. In this article, we review the pharmacology and function of the GABA system and its perturbation in seizure disorders, and highlight how improved understanding of this system offers opportunities to develop more efficacious and better tolerated antiseizure medications. We also review the available data for the two most recently approved antiseizure medications that act, at least in part, through GABAergic mechanisms, namely cenobamate and ganaxolone. Differences in the mode of drug discovery, pharmacological profile, pharmacokinetic properties, drug-drug interaction potential, and clinical efficacy and tolerability of these agents are discussed.
Topics: Animals; Humans; Chlorides; Epilepsy; Brain; Anticonvulsants; Seizures; Mammals
PubMed: 37603262
DOI: 10.1007/s40263-023-01027-2 -
Pediatric Neurology Jun 2024Febrile seizures (FS) are the most common neurological disorder in pediatric age. FS affect 2% to 12% of children and result from a complex interplay of genetic and... (Review)
Review
BACKGROUND
Febrile seizures (FS) are the most common neurological disorder in pediatric age. FS affect 2% to 12% of children and result from a complex interplay of genetic and environmental factors. Effective management and unambiguous recommendations are crucial for allocating health care resources efficiently and ensuring cost-effectiveness in treating FS.
METHODS
This systematic review compares existing guidelines to provide insights into FS management. Seven guidelines published between 1991 and 2021, from Japan, United Kingdom, United States, Mexico, India, and Italy, were included. Data extraction covered definitions, diagnostic criteria, hospital admission criteria, diagnostic tests, management, and prophylaxis recommendations.
RESULTS
Hospital admission criteria varied but typically included age <18 months and complex FS. Neuroimaging and lumbar puncture recommendations varied, with most guidelines suggesting limited use. Pharmacologic prophylaxis was generally discouraged for simple FS but considered only for high-risk cases, due to the benign nature of FS and the potential side effects of antiseizure medications.
CONCLUSIONS
Guidelines on FS exhibit similarities and differences, highlighting the need for standardized management and improved parental education to enhance clinical outcomes and reduce economic and social costs associated with FS. Future research should focus on creating updated international guidelines and ensuring their practical implementation.
Topics: Humans; Seizures, Febrile; Practice Guidelines as Topic; Infant
PubMed: 38653182
DOI: 10.1016/j.pediatrneurol.2024.03.024 -
Italian Journal of Pediatrics May 2024Febrile seizures (FS) are commonly perceived by healthcare professionals as a self-limited condition with a generally 'benign' nature. Nonetheless, they frequently lead... (Review)
Review
Febrile seizures (FS) are commonly perceived by healthcare professionals as a self-limited condition with a generally 'benign' nature. Nonetheless, they frequently lead to pediatric consultations, and their management can vary depending on the clinical context. For parents and caregivers, witnessing a seizure can be a distressing experience, significantly impacting their quality of life. In this review, we offer an in-depth exploration of FS management, therapeutic interventions, and prognostic factors, with the aim of providing support for physicians and enhancing communication with families. We conducted a comprehensive literature search using the PubMed and Web of Science databases, spanning the past 50 years. The search terms utilized included "febrile seizure," "complex febrile seizure," "simple febrile seizure," in conjunction with "children" or "infant." Only studies published in English or those presenting evidence-based data were included in our assessment. Additionally, we conducted a cross-reference search to identify any additional relevant data sources. Our thorough literature search resulted in a compilation of references, with carefully selected papers thoughtfully integrated into this review.
Topics: Humans; Seizures, Febrile; Child; Infant; Practice Guidelines as Topic; Anticonvulsants; Prognosis
PubMed: 38735928
DOI: 10.1186/s13052-024-01666-1 -
Tidsskrift For Den Norske Laegeforening... Mar 2024This clinical review examines the treatment of status epilepticus, a condition in which epileptic seizures are prolonged and pose a significant risk of brain damage and...
This clinical review examines the treatment of status epilepticus, a condition in which epileptic seizures are prolonged and pose a significant risk of brain damage and death. International guidelines recommend the use of benzodiazepines as first-line treatment, and these should be administered promptly and in appropriate doses. Second-line treatment involves the use of high-dose anti-seizure medications to stop and prevent seizures. If seizure activity persists, general anaesthesia should be administered as soon as possible. All neurological hospital departments should have established and rehearsed protocols for treating status epilepticus.
Topics: Adult; Humans; Anticonvulsants; Status Epilepticus; Epilepsy; Benzodiazepines
PubMed: 38506004
DOI: 10.4045/tidsskr.23.0782 -
Neurobiology of Disease Aug 2023The advent of optogenetic tools has had a profound impact on modern neuroscience research, revolutionizing our understanding of the brain. These tools offer a remarkable... (Review)
Review
The advent of optogenetic tools has had a profound impact on modern neuroscience research, revolutionizing our understanding of the brain. These tools offer a remarkable ability to precisely manipulate specific groups of neurons with an unprecedented level of temporal precision, on the order of milliseconds. This breakthrough has significantly advanced our knowledge of various physiological and pathophysiological processes in the brain. Within the realm of epilepsy research, optogenetic tools have played a crucial role in investigating the contributions of different neuronal populations to the generation of seizures and hyperexcitability. By selectively activating or inhibiting specific neurons using optogenetics, researchers have been able to elucidate the underlying mechanisms and identify key players involved in epileptic activity. Moreover, optogenetic techniques have also been explored as innovative therapeutic strategies for treating epilepsy. These strategies aim to halt seizure progression and alleviate symptoms by utilizing the precise control offered by optogenetics. The application of optogenetic tools has provided valuable insights into the intricate workings of the brain during epileptic episodes. For instance, researchers have discovered how distinct interneuron populations contribute to the initiation of seizures (ictogenesis). They have also revealed how remote circuits in regions such as the cerebellum, septum, or raphe nuclei can interact with hyperexcitable networks in the hippocampus. Additionally, studies have demonstrated the potential of closed-loop systems, where optogenetics is combined with real-time monitoring, to enable precise, on-demand control of seizure activity. Despite the immense promise demonstrated by optogenetic approaches, it is important to acknowledge that many of these techniques are still in the early stages of development and have yet to reach potential clinical applications. The transition from experimental research to practical clinical use poses numerous challenges. In this review, we aim to introduce optogenetic tools, provide a comprehensive survey of their application in epilepsy research, and critically discuss their current potential and limitations in achieving successful clinical implementation for the treatment of human epilepsy. By addressing these crucial aspects, we hope to foster a deeper understanding of the current state and future prospects of optogenetics in epilepsy treatment.
Topics: Humans; Optogenetics; Seizures; Epilepsy; Brain; Neurons
PubMed: 37479090
DOI: 10.1016/j.nbd.2023.106234 -
Neurobiology of Disease Sep 2023The progressive myoclonic epilepsies (PMEs) are a group of rare neurodegenerative diseases characterized by myoclonus, epileptic seizures, and progressive neurological... (Review)
Review
The progressive myoclonic epilepsies (PMEs) are a group of rare neurodegenerative diseases characterized by myoclonus, epileptic seizures, and progressive neurological deterioration with cerebellar involvement. They include storage diseases like Gaucher disease, Lafora disease, and forms of neuronal ceroid lipofuscinosis (NCL). To date, 13 NCLs have been reported (CLN1-CLN8, CLN10-CLN14), associated with mutations in different genes. These forms, which affect both children and adults, are characterized by seizures, cognitive and motor impairments, and in most cases visual loss. In NCLs, as in other PMEs, central nervous system (CNS) neurodegeneration is widespread and involves different subpopulations of neurons. One of the most affected regions is the cerebellar cortex, where motor and non-motor information is processed and transmitted to deep cerebellar nuclei through the axons of Purkinje cells (PCs). PCs, being GABAergic, have an inhibitory effect on their target neurons, and provide the only inhibitory output of the cerebellum. Degeneration of PCs has been linked to motor impairments and epileptic seizures. Seizures occur when some insult upsets the normal balance in the CNS between excitatory and inhibitory impulses, causing hyperexcitability. Here we review the role of PCs in epilepsy onset and progression following their PME-related loss. In particular, we focus on the involvement of PCs in seizure phenotype in NCLs, highlighting findings from case reports and studies of animal models in which epilepsy can be linked to PC loss.
Topics: Animals; Neuronal Ceroid-Lipofuscinoses; Purkinje Cells; Myoclonic Epilepsies, Progressive; Epilepsy; Seizures
PubMed: 37573956
DOI: 10.1016/j.nbd.2023.106258 -
Epilepsy & Behavior : E&B Jan 2024Seizure unpredictability plays a major role in disability and decreased quality of life in people with epilepsy. Dogs have been used to assist people with disabilities... (Review)
Review
Seizure unpredictability plays a major role in disability and decreased quality of life in people with epilepsy. Dogs have been used to assist people with disabilities and have shown promise in detecting seizures. There have been reports of trained seizure-alerting dogs (SADs) successfully detecting when a seizure is occurring or indicating imminent seizures, allowing patients to take preventative measures. Untrained pet dogs have also shown the ability to detect seizures and provide comfort and protection during and after seizures. Dogs' exceptional olfactory abilities and sensitivity to human cues could contribute to their seizure-detection capabilities. This has been supported by studies in which dogs have distinguished between epileptic seizure and non-seizure sweat samples, probably though the detection of volatile organic compounds (VOCs). However, the existing literature has limitations, with a lack of well-controlled, prospective studies and inconsistencies in reported timings of alerting behaviours. More research is needed to standardize reporting and validate the results. Advances in VOC profiling could aid in distinguishing seizure types and developing rapid and unbiased seizure detection methods. In conclusion, using dogs in epilepsy management shows considerable promise, but further research is needed to fully validate their effectiveness and potential as valuable companions for people with epilepsy.
Topics: Animals; Humans; Dogs; Prospective Studies; Quality of Life; Seizures; Epilepsy; Smell
PubMed: 38071830
DOI: 10.1016/j.yebeh.2023.109563 -
Proceedings of the National Academy of... Jul 2023There remains an urgent need for new therapies for treatment-resistant epilepsy. Sodium channel blockers are effective for seizure control in common forms of epilepsy,...
There remains an urgent need for new therapies for treatment-resistant epilepsy. Sodium channel blockers are effective for seizure control in common forms of epilepsy, but loss of sodium channel function underlies some genetic forms of epilepsy. Approaches that provide bidirectional control of sodium channel expression are needed. MicroRNAs (miRNA) are small noncoding RNAs which negatively regulate gene expression. Here we show that genome-wide miRNA screening of hippocampal tissue from a rat epilepsy model, mice treated with the antiseizure medicine cannabidiol, and plasma from patients with treatment-resistant epilepsy, converge on a single target-miR-335-5p. Pathway analysis on predicted and validated miR-335-5p targets identified multiple voltage-gated sodium channels (VGSCs). Intracerebroventricular injection of antisense oligonucleotides against miR-335-5p resulted in upregulation of , , and in the mouse brain and an increased action potential rising phase and greater excitability of hippocampal pyramidal neurons in brain slice recordings, consistent with VGSCs as functional targets of miR-335-5p. Blocking miR-335-5p also increased voltage-gated sodium currents and , and expression in human induced pluripotent stem cell-derived neurons. Inhibition of miR-335-5p increased susceptibility to tonic-clonic seizures in the pentylenetetrazol seizure model, whereas adeno-associated virus 9-mediated overexpression of miR-335-5p reduced seizure severity and improved survival. These studies suggest modulation of miR-335-5p may be a means to regulate VGSCs and affect neuronal excitability and seizures. Changes to miR-335-5p may reflect compensatory mechanisms to control excitability and could provide biomarker or therapeutic strategies for different types of treatment-resistant epilepsy.
Topics: Humans; Mice; Rats; Animals; Induced Pluripotent Stem Cells; Seizures; Epilepsy; MicroRNAs; Voltage-Gated Sodium Channels; NAV1.1 Voltage-Gated Sodium Channel; NAV1.3 Voltage-Gated Sodium Channel
PubMed: 37463203
DOI: 10.1073/pnas.2216658120 -
Epilepsy & Behavior : E&B Jul 2023Self-management education programs have been highly successful in preparing people to manage medical conditions with recurring events. A detailed curriculum for epilepsy... (Review)
Review
Self-management education programs have been highly successful in preparing people to manage medical conditions with recurring events. A detailed curriculum for epilepsy patients, and their caretakers, is lacking. Here we assess what is available for patients who have disorders with recurring events and offer an approach to developing a potential self-care curriculum for patients with seizures and their caregivers. Among the anticipated components are a baseline efficacy assessment and training tailored to increasing self-efficacy, medication compliance, and stress management. Those at risk of status epilepticus will also need guidance in preparing a personalized seizure action plan and training in how to decide when rescue medication is appropriate and how to administer the therapy. Peers, as well as professionals, could teach and provide support. To our knowledge, no such programs are currently available in English. We encourage their creation, dissemination, and widespread use.
Topics: Humans; Child; Caregivers; Self-Management; Epilepsy; Seizures; Educational Status
PubMed: 37196451
DOI: 10.1016/j.yebeh.2023.109232