The propagation of epileptiform events is a highly interesting phenomenon from the pathophysiological point of view, as it involves several mechanisms of recruitment of neural networks. Extensive and research has been performed, suggesting that multiple networks as well as cellular candidate mechanisms govern this process, including the co-existence of wave propagation, coupled oscillator dynamics, and more. The clinical importance of seizure propagation stems mainly from the fact that the epileptic manifestations cannot be attributed solely to the activity in the seizure focus itself, but rather to the propagation of epileptic activity to other brain structures. Propagation, especially when causing secondary generalizations, poses a risk to patients due to recurrent falls, traumatic injuries, and poor neurological outcome. Anti-seizure medications (ASMs) affect propagation in diverse ways and with different potencies. Importantly, for drug-resistant patients, targeting seizure propagation may improve the quality of life even without a major reduction in simple focal events. Motivated by the extensive impact of this phenomenon, we sought to review the literature regarding the propagation of epileptic activity and specifically the effect of commonly used ASMs on it. Based on this body of knowledge, we propose a novel classification of ASMs into three main categories: major, minor, and intermediate efficacy in reducing the propagation of epileptiform activity.
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http://dx.doi.org/10.3389/fneur.2021.674182 | DOI Listing |
Epilepsia
December 2024
Department of Neurology, University of Virginia, Charlottesville, Virginia, USA.
Objective: Focal cortical seizures travel long distances from the onset zone, but the long-distance propagation pathways are uncertain. In vitro and in vivo imaging techniques have investigated the local spread of seizures but did not elucidate long-distance spread. Furthermore, classical studies in slices suggested seizure spread locally along deep cortical layers, whereas more recent in vivo imaging studies posit a role for superficial cortical layers in local spread.
View Article and Find Full Text PDFCannabidiol (CBD) is a prominent non-psychoactive small molecule produced by cannabis plants used clinically as an antiepileptic. Here, we show CBD and other cannabinoids are potent inhibitors of mechanosensitive two-pore domain K+ (K2P) channels, including TRAAK and TREK-1 that contribute to spike propagation in myelinated axons. Five TRAAK mutations that cause epilepsy or the neurodevelopmental syndrome FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth) retain sensitivity to cannabinoid inhibition.
View Article and Find Full Text PDFMedication-refractory focal epilepsy poses a significant challenge, with approximately 30% of patients ineligible for surgery due to the involvement of eloquent cortex in the epileptogenic network. For such patients with limited surgical options, electrical neuromodulation represents a promising alternative therapy. In this study, we investigate the potential of non-invasive temporal interference (TI) electrical stimulation to reduce epileptic biomarkers in patients with epilepsy by comparing intracerebral recordings obtained before, during, and after TI stimulation, and to those recorded during low and high kHz frequency (HF) sham stimulation.
View Article and Find Full Text PDFEpilepsia
December 2024
Division of Neurology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Objective: SCN2A encodes the voltage-gated sodium (Na+) channel α subunit Na1.2, which is important for the generation and forward and back propagation of action potentials in neurons. Genetic variants in SCN2A are associated with a spectrum of neurodevelopmental disorders.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
December 2024
Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia.
Epilepsy affects more than 70 million individuals of all ages worldwide and remains one of the most severe chronic noncommunicable neurological diseases globally. Several neurotransmitters, membrane protein channels, receptors, enzymes, and, more recently noted, various pathways, such as inflammatory and mTORC complexes, play significant roles in the initiation and propagation of seizures. Over the past two decades, significant developments have been made in the diagnosis and treatment of epilepsy.
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