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Cureus
December 2024
Internal Medicine, King Abdulaziz Specialist Hospital, Taif, SAU.
Cerebral palsy (CP) is a debilitating disorder that can lead to life-long disability, with a high incidence in Saudi Arabia. Secondary epilepsy and cardiac complications are common in CP patients. We present a rare case of a 17-year-old female with CP, attention-deficit hyperactivity disorder (ADHD), secondary epilepsy, and a history of post-cardiac arrest, with home medications carbamazepine, risperidone, and sodium valproate.
View Article and Find Full Text PDFEpilepsia
January 2025
Division of Pediatric Neurology and Developmental Medicine, Department of Pediatrics, Duke University, Durham, North Carolina, USA.
Objective: This study was undertaken to test the following hypotheses in the Atp1a3 mouse (which carries the most common human ATP1A3 (the major subunit of the neuronal Na/K-adenosine triphosphatase [ATPase]) mutation, D801N): sudden unexpected death in epilepsy (SUDEP) occurs during seizures and is due to terminal apneas in some and due to lethal cardiac arrhythmias in others; and Atp1a3 mice have central cardiorespiratory dysregulation and abnormal respiratory drive.
Methods: Comparison was made of littermate wild-type and Atp1a3 groups using (1) simultaneous in vivo video-telemetry recordings of electroencephalogram, electrocardiogram, and breathing; (2) whole-body plethysmography; and (3) hypoglossal nerve recordings.
Results: In Atp1a3 mice, (1) SUDEP consistently occurred during seizures that were more severe than preterminal seizures; (2) seizure clustering occurred in periods preceding SUDEP; (3) slowing of breathing rate (BR) and heart rate was observed preictally before preterminal and terminal seizures; and (4) the sequence during terminal seizures was as follows: bradypnea with bradycardia/cardiac arrhythmias, then terminal apnea, followed by terminal cardiac arrhythmias.
J Physiol
January 2025
Department of Biological Sciences, Southern Methodist University, Dallas, TX, USA.
Sudden unexpected death in epilepsy (SUDEP) is a devastating complication of epilepsy with possible sex-specific risk factors, although the exact relationship between sex and SUDEP remains unclear. To investigate this, we studied Kcna1 knockout (Kcna1) mice, which lack voltage-gated Kv1.1 channel subunits and are widely used as a SUDEP model that mirrors key features in humans.
View Article and Find Full Text PDFBackground: Long QT Syndrome Type-2 (LQT2) is due to loss-of-function variants. encodes K 11.1 that forms a delayed-rectifier potassium channel in the brain and heart.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
December 2024
University of Münster, Institute of Pharmaceutical and Medicinal Chemistry, Pharma Campus, Corrensstr. 48, 48149 Münster, Germany.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels play a critical role in regulating neuronal and cardiac rhythmicity, with their function being modulated by cyclic nucleotide binding. Dysfunction of HCN ion channels leads to the genesis of several diseases such as arrhythmia, bradycardia, or epilepsy. This study employs a multidisciplinary approach integrating mutagenesis, ligand binding assays, and molecular dynamics (MD) simulations combined with dynamic pharmacophore studies to investigate the impact of single residue mutations within the cyclic nucleotide-binding domain (CNBD) of HCN4 channels.
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