摘要 :
Current antiepileptic drug (AED) therapy requires trial and error in determining the most effective AED and dosage for a patient, and almost one-fourth of patients are resistant to AED therapy. The introduction of individualized m...
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Current antiepileptic drug (AED) therapy requires trial and error in determining the most effective AED and dosage for a patient, and almost one-fourth of patients are resistant to AED therapy. The introduction of individualized medicine for epilepsy based on genetic information is a new avenue to improve current AED therapy. However, several crucial issues remain to be resolved before the development of individualized medicine for epilepsy can proceed further. The epilepsy genes responsible for common phenotypes have not yet been identified, and ongoing pharmacogenetic studies continue to search for an explanation of why 25 to 30% of patients do not respond to AEDs. There is no convincing clinical evidence indicating the impact of P-glycoprotein on prediction of clinical response. This article provides a critical review of the status and perspectives for the development of individualized medicine for epilepsy based on genetic polymorphisms/mutations in relation to core elements such as pharmacodynamic pathway, pharmacokinetic pathway, prediction of idiosyncratic reaction to AED, and mechanisms of action of AEDs.
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摘要 :
Epilepsy is a recurring neurological disease caused by the abnormal electrical activity in the brain. This disease has caused about 50 new cases in 100,000 populations every year with the clinical manifestations of awareness loss,...
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Epilepsy is a recurring neurological disease caused by the abnormal electrical activity in the brain. This disease has caused about 50 new cases in 100,000 populations every year with the clinical manifestations of awareness loss, bruising, and mobility abnormalities. Due to the lack understanding of the pathophysiology behind the illness, a wide variety of medications are available to treat epilepsy. Epileptogenesis is the process by which a normally functioning brain undergoes alterations leading to the development of epilepsy, involving various factors. This is related to the inflammation which is driven by cytokines like IL-1 and tumor necrosis factor-α (TNF-α) leads to neuronal hyperexcitability. Pro-inflammatory cytokines from activated microglia and astrocytes in epileptic tissue initiate an inflammatory cascade, heightening neuronal excitability and triggering epileptiform activity. The blood-brain barrier (BBB) maintains central nervous system integrity through its tight endothelial connections, but inflammation impact BBB structure and function which leads to immune cell infiltration. The mammalian target of rapamycin (mTOR) pathway’s excessive activation influences epileptogenesis, impacting neuronal excitability, and synapse formation, with genetic mutations contributing to epilepsy syndromes and the modulation of autophagy playing a role in seizure onset. The apoptotic pathway contribute to cell death through glutamate receptor-mediated excitotoxicity, involving pro-apoptotic proteins like p53 and mitochondrial dysfunction, leading to the activation of caspases and the disruption of calcium homeostasis. Ionic imbalances within neural networks contribute to the complexity of epileptic seizures, involving alterations in voltage-gated sodium and potassium channels, and the formation of diverse ion channel subtypes. Epileptogenesis triggers molecular changes in hippocampus, including altered neurogenesis and enhanced expression of neurotrophic factors and proteins. Oxidative stress leads to cellular damage, disrupted antioxidant systems, and mitochondrial dysfunction, making it a key player in epileptogenesis and potential neuroprotective interventions. Thalamocortical circuitry disruption is central to absence epilepsy, the normal circuit becomes faulty and results in characteristic brain wave patterns.
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摘要 :
Epilepsy is a neurological disease characterized by excessive and abnormal hyper-synchrony of electrical discharges of the brain and a predisposition to generate epileptic seizures resulting in a broad spectrum of neurobiological ...
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Epilepsy is a neurological disease characterized by excessive and abnormal hyper-synchrony of electrical discharges of the brain and a predisposition to generate epileptic seizures resulting in a broad spectrum of neurobiological insults, imposing psychological, cognitive, social and also economic burdens to the sufferer. Voltage-gated sodium channels (VGSCs) are essential for the generation and propagation of action potentials throughout the central nervous system. Dysfunction of these channels has been implicated in the pathogenesis of epilepsy. VGSC inhibitors have been demonstrated to act as anticonvulsants to suppress the abnormal neuronal firing underlying epileptic seizures, and are used for the management and treatment of both genetic-idiopathic and acquired epilepsies. We discuss the forms of idiopathic and acquired epilepsies caused by VGSC mutations and the therapeutic efficacy of VGSC blockers in idiopathic, acquired and pharmacoresistant forms of epilepsy in this review. We conclude that there is a need for better alternative therapies that can be used alone or in combination with VGSC inhibitors in the management of epilepsies. The current anti-seizure medications (ASMs) especially for pharmacoresistant epilepsies and some other types of epilepsy have not yielded expected therapeutic efficacy partly because they do not show subtype-selectivity in blocking sodium channels while also bringing side effects. Therefore, there is a need to develop novel drug cocktails with enhanced selectivity for specific VGSC isoforms, to achieve better treatment of pharmacoresistant epilepsies and other types of epileptic seizures.
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Epilepsy is a chronic neurological disorder that has an extensive impact on a patient’s life. Accumulating evidence has suggested that inflammation participates in the progression of spontaneous and recurrent seizures. Pro-convul...
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Epilepsy is a chronic neurological disorder that has an extensive impact on a patient’s life. Accumulating evidence has suggested that inflammation participates in the progression of spontaneous and recurrent seizures. Pro-convulsant incidences can stimulate immune cells, augment the release of pro-inflammatory cytokines, elicit neuronal excitation as well as blood-brain barrier (BBB) dysfunction, and finally trigger the generation or recurrence of seizures. Understanding the pathogenic roles of inflammatory mediators, including inflammatory cytokines, cells, and BBB, in epileptogenesis will be beneficial for the treatment of epilepsy. In this systematic review, we performed a literature search on the PubMed database using the following keywords: “epilepsy” or “seizures” or “epileptogenesis”, and “immunity” or “inflammation” or “neuroinflammation” or “damage-associated molecular patterns” or “cytokines” or “chemokines” or “adhesion molecules” or “microglia” or “astrocyte” or “blood-brain barrier”. We summarized the classic inflammatory mediators and their pathogenic effects in the pathogenesis of epilepsy, based on the most recent findings from both human and animal model studies.
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摘要 :
The relationship between epilepsy and psychoses has long been debated, and descriptions regarding symptoms of interictal psychoses in patients with epilepsy date back to even the Babylonian era. However, scant attention has been p...
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The relationship between epilepsy and psychoses has long been debated, and descriptions regarding symptoms of interictal psychoses in patients with epilepsy date back to even the Babylonian era. However, scant attention has been paid to this issue lately. Adequate recognition of psychoses in epilepsy is essential for physicians caring for the affected patients, because the impact on their quality of life is too devastating to be overlooked. Investigations of the associations between epilepsy and psychoses were initially conducted by French and German neuropsychiatrists in the 19th century, while much of the literature came from England in the second half of the last century. It is widely recognized that the epoch-making reports by Slater, Beard and Glithero in 1963 raised important clinical questions regarding so-called "schizophrenia-like" psychoses of epilepsy. Although some of those questions have been answered, many remain controversial. In this review, current knowledge regarding schizophrenia-like psychoses of epilepsy is examined in light of the questions posed by Slater and colleagues.
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