Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy (SMEI), is an intractable epilepsy syndrome. Most cases are associated with mutations in the SCN1A gene, which is responsible for the expression of the sodium voltage-gated channel alpha subunit 1, Nav1.1. These mutations lead to altered neuronal firing and a state of hyperexcitability. DS has been studied using patient samples, animal models, and more recently, iPS cells derived from DS patients. In this work, we sought to understand the impact that Nav1.1 loss-of-function has on the elementary chemical constitution of DS patient-derived neural cells. iPS cells from DS patients and controls were differentiated into neural-induced spheroids, and synchrotron X-ray radiation was used to assess alterations in their elemental concentration. We observed that DS-derived neural cells present elevated levels of potassium (K), copper (Cu), and zinc (Zn). These findings suggest that an elemental imbalance may be involved in the pathogenesis of DS, as higher levels of K, Cu, and Zn have been implicated in seizure episodes and epilepsy. We conclude that modeling DS using cell reprogramming is a relevant approach to understanding the basic mechanisms involved in this disease and perhaps provide novel treatment strategies.

Severe myoclonic epilepsy of infancy (SMEI, Dravet syndrome), which is mainly caused by the SCN1A mutation, is a severe epileptic encephalopathy that manifests in infancy and leads to intractable seizures and developmental impairment. To discover new therapeutic chemotypes, we established a Nav1.1 (scn1lab) KO zebrafish model for chemical screening and identified novel 1,3,4-oxadiazol-2(3H)-one derivatives. Among them, compound 20e showed the most potent antiseizure efficacy in zebrafish behavioral assays and significantly reduced locomotion-related seizure parameters compared with repositioned drugs. In SCN1A+/- mice, 20e reduced seizure severity, delayed onset, and suppressed hyperactivity. Notably, 20e normalized pathological spike and burst activity in SMEI patient-derived iPSC neurons. Mechanistically, 20e appears to elevate 5-HT levels via TPH2 upregulation. It demonstrated reasonable BBB penetration, favorable oral PK, and good safety without notable hERG inhibition, cytotoxicity, mutagenicity, or acute toxicity. Taken together, compound 20e shows promise as a therapeutic agent for SMEI.

Dravet syndrome, also known as severe myoclonic epilepsy of infancy, is an epileptic encephalopathy characterized by severe epilepsy accompanied by impaired psychomotor and neurologic development. Onset is in the first year of life in apparently healthy infants. Seizures in Dravet syndrome are highly pharmacoresistant, and the SUDEP mortality rate is high. Here, we present the first case of the successful use of cenobamate in a pediatric patient (9-year-old female) with Dravet syndrome and pharmacoresistant epilepsy despite the prior use and failure of typical medications for Dravet syndrome, including fenfluramine, valproate, and clobazam, among others. At 6-month follow-up, the frequency of generalized tonic-clonic seizures decreased from 8 per month to 1 per month upon reaching a daily dose of 50 mg (1.9 mg/kg/day), which represents an 87.5% reduction. No side effects were reported. Given the single-patient case report nature of this study, further investigations are needed to extrapolate the usefulness of cenobamate across different age groups and genetic variants. Myoclonic epilepsy of infancy (MEI) is a rare self-limited epileptic syndrome characterized by brief myoclonic seizures in previously healthy and developmentally normal children with onset in the first 3 years of life. MEI is also known as benign myoclonic epilepsy in infants (BMEI), a term first used by Dravet and Bureau in a 1981 study. Before this study, several similar cases had been reported but with varying terminology, including "myoclonic epilepsy of childhood," which was used by Jeavons.  MEI does not have a benign course or prognosis in some children, so the word benign was removed from the name. The International League Against Epilepsy (ILAE) has included MEI among other neonatal and infantile epileptic syndromes under the classification of idiopathic generalized epilepsies with age-related onset. However, MEI can present as a generalized epilepsy in a child with a developmental encephalopathy or normal intellect.

The objective of this case report is to describe and document a case of respiratory syncytial virus (RSV) in a pediatric patient with Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy. Febrile seizures are often a complication in a patient with DS and can lead to status epilepticus, necessitating measures to prevent triggers such as fever, electrolyte imbalance, or dehydration. An increased awareness and understanding of DS can facilitate the identification of warning signs. A two-year-old female with a past medical history of DS with focal and generalized features presented to the pediatric emergency department (ED) with a five-day history of cough, fever, and decreased oral intake. The patient's parents accompanied her and expressed concerns regarding the risk of seizures associated with a rise in body temperature, as they had been alternating between acetaminophen and ibuprofen to manage her fever with a maximum recorded temperature of 101.5℉. She exhibited signs of increased work of breathing, necessitating the administration of supplemental oxygen via nasal cannula. Blood samples were obtained and resulted in the development of metabolic acidosis. A respiratory panel confirmed the presence of an RSV infection, promoting the administration of breathing treatment with albuterol and ipratropium bromide. The patient was admitted for dehydration and was started on ½ normal saline/potassium chloride 20 mEq at 40 mL/hr. Additionally, her home medication regimen was resumed to minimize the risk of seizures. Given the patient's complications and increased risk of seizure, she was transferred to higher-level care where her status improved after the placement of a percutaneous endoscopic gastrostomy (PEG). This case underscores the complexities involved in managing patients with DS, particularly when complicated by respiratory illness and electrolyte imbalances that can lower the seizure threshold. This patient received a combination of diet and medications to prevent seizures, as well as allow for recovery and correction of the underlying metabolic acidosis. The transfer to a higher level of care in this case was necessary to allow for the specialized resources and expertise needed to handle this case.