Search

Background: Voltage-gated sodium channels are involved in the initial depolarisation of neurones. As such, they play important roles in neurotransmission. Variants in the genes encoding these channels may lead to altered functionality and neurodevelopmental disorders. Pathogenic variants of SCN8A, which encodes the voltage-gated Na+ channel Nav1.6, have been associated with various encephalopathies characterised by developmental delay and epileptic seizures. Herein, we discuss the genotype-phenotype associations in a group of 17 novel Polish patients with SCN8A mutations, further expanding the molecular and phenotypic spectrum of SCN8A-related diseases., Methods: The participants were recruited from five clinical centres in Poland. Pathogenic and likely pathogenic SCN8A variants were identified using a next-generation sequencing (NGS) panel and exome sequencing, respectively. Magnetic resonance imaging (MRI) and electroencephalography (EEG) recordings were performed to obtain relevant clinical data on brain malformations and epileptic seizures., Results: Three phenotypes were observed in the study group: developmental and epileptic encephalopathy, early onset epileptic encephalopathy, and neurodevelopmental disorders without epilepsy. Patients in the first two phenotypic subgroups presented with epileptic seizures within the first few months of life. Their semiology evolved with age, comprising mostly tonic, clonic, and tonic-clonic seizures, with eyelid myoclonia, myoclonic seizures, and epileptic spasms. The most prevalent neurological feature was developmental delay. Alterations in muscle tone were more frequent than in previous reports., Conclusions: Seventeen patients with 11 novel mutations in SCN8A had alterations in muscular tone accompanied by typical features of SCN8A-related encephalopathies (i.e., developmental delay and a wide range of seizures)., Competing Interests: Declaration of competing interest The Authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier Ltd.)

In times of severe antiseizure medication (ASM) shortage due to emergency situations (e.g., disasters, conflicts, sudden disruption to international supply chains), management of people with epilepsy with available ASMs can be difficult. A group of experts was brought together by the International League Against Epilepsy (ILAE) to formulate recommendations for such circumstances. Every effort was made to base these recommendations on direct published literature or extrapolations from basic information available about ASMs. Actual published literature in this area is, however, limited, and at times, assumptions were made by the experts to generate these recommendations. During times of shortage of ASMs, switching between different ASMs (e.g., oxcarbazepine and carbamazepine) can occasionally be considered as a mitigation procedure. However, for many ASMs, the option of an overnight switch to another drug does not exist. Switching from brand to generic or between generic products has often been shown to be safe, if required. Finally, when supplies of benzodiazepines or equipment to administer medications intravenously are not available, rectal administration of some ASMs may be an emergency alternative route for treating serial seizures and status epilepticus. Decision-making with regard to treatment and possible options should be driven by what is best for the patient.