Treatment of Seizures in the Neonate: Special Report From the ILAE Task Force on Neonatal Seizures, 2022

The International League Against Epilepsy (ILAE) task force on neonatal seizures has recently published draft guidelines and consensusbased recommendations on the treatment of neonatal seizures. This update provides a summary of the recommendations and the changes in management compared to the previous WHO ILAE guidelines, published in 2011, with emphasis on practical decision making requirements for a pediatrician.

Levetiracetam and Midazolam vs Midazolam Alone for First-Line Treatment of Children With Generalized Convulsive Status Epilepticus (Lev-Mid Study): A Randomized Controlled Trial

Background:Benzodiazepines are the first-line anti-seizure medication (ASM) for generalized convulsive status epilepticus (GCSE), but they fail to end seizures in a third of cases. Combining benzodiazepines with another ASM that acts by a different pathway could be a potential strategy for rapid control of GCSE. Objectives: To evaluate the efficacy of adding levetiracetam to midazolam in the initial treatment of pediatric GCSE. Design: Double-blind randomized controlled trial. Setting: Pediatric emergency room at Sohag University Hospital between June, 2021 and August, 2022. Participants: Children aged between 1 month and 16 years with GCSE lasting more than 5 min. Interventions: Intravenous levetiracetam (60 mg/kg over 5 min) and midazolam (Lev-Mid group) or placebo and midazolam (PlaMid group) as first-line anticonvulsive therapy. Outcome measures: Primary: cessation of clinical seizures at 20- min study time point. Secondary: cessation of clinical seizures at 40-min study time point, need for a second midazolam dose, seizure control at 24-hr, need for intubation, and adverse effects. Results: Cessation of clinical seizures at 20-min occurred in 55 children (76%) in Lev-Mid group compared with 50 (69%) in the PlaMid group [RR (95% CI) 1.1 (0.9-1.34); P=0.35]. No significant difference was found between the two groups regarding the need for a second midazolam dose [44.4% vs 55.6%; RR (95% CI) 0.8 (0.58- 1.11); P=0.18] as well as cessation of clinical seizures at 40-min [96% vs 92%; RR (95% CI)1.05 (0.96-1.14); P=0.49] and seizure control at 24-hr [85% vs 76%; RR (95% CI) 1.12 (0.94-1.3); P=0.21]. Intubation was required for three patients in the Lev-Mid group and six patients in the Pla-Mid group [RR (95%CI) 0.5 (0.13- 1.92); P=0.49]. No other adverse effects or mortality were observed during the 24-hour study timeframe. Conclusion: Combined levetiracetam and midazolam for initial management of pediatric GCSE presents no significant advantage over midazolam alone in cessation of clinical seizures at 20-min.

Molecular and Genetic Mechanisms of Neurotoxicity During Anti-seizure Medications Use

ABSTRACT Epilepsy is a multifactorial pathology that has allowed the development of various drugs aiming to combat it. This effort was formally initiated in the 1940s when phenytoin began to be used. It eventually turned out to be a drug with great anticonvulsant efficacy. At present, several potentially good new generation anti-seizure medications (ASMs) have been developed. Most of them present more tolerability and less toxic effects. However, they continue to have adverse effects at different levels. In addition, some seizures are difficult to treat with ASMs, representing 30% of the total cases of people who suffer from epilepsy. This review aims to explore the genetic and molecular mechanisms of ASMs neurotoxicity, proposing the study of damage caused by epileptic seizures, in addition to the deterioration generated by anti-seizure drug administration within the central nervous system. It is beyond question that there is a need to develop drugs that lower the lower the risk of secondary and toxic effects of ASMs. Simultaneously, we must find strategies that produce fewer harmful interactions and more health benefits when taking anti-seizure drugs.

Research progress on the relationship between pediatric epilepsy and vitamin D / 中国临床药理学与治疗学

Epilepsy is a long-term, chronic, recurrent, multi-factorial, multi-symptomatic nervous system disease, and was caused by abnormal discharge of brain neurons. Etiology can cause irreversible brain dysfunction and even death. There are about 6.5 million children with epilepsy in China, with incidence rate twice that of adult, presenting serious threaten to children's growth and development. Vitamin D has been well-known for crucial importance to development of nervous, skeletal, and immune system. Studies have found that pediatric epilepsy as well as other neurological diseases were closely related with vitamin D deficiency. First, a large number of studies have shown that vitamin D in children with epilepsy is affected by epilepsy itself; second, the use of anti-seizure medicines can alter metabolism of vitamin D by inducing cytochrome oxidases; third, the inducement was concerned to varieties, combination and duration of anti-seizure medicines; fourth, it was expected that supplement of vitamin D during antiepileptic treatment would guarantee an improvement of treating given that anti-seizure medicines may lead to deficiency of vitamin D. Large numbers of researches have reported on the correlation ship between pediatric epilepsy and vitamin D. However, there is still a lack of systematic review. This article aims to retrospect the research progress of relationship between pediatric epilepsy and vitamin D, and provide valuable feedbacks on further treatment of pediatric epilepsy.

Transformation of epilepsy treatment model: anti-epileptogenesis and disease-modifying therapy / 中华神经科杂志

Most anti-seizure medications do not change the course of epilepsy and are basically "symptomatic treatment". Even if a variety of new anti-seizure medications continue to come out, there are still more than 30% of patients develop drug-resistant epilepsy. Therefore, investigating new therapeutic targets and developing effective drugs to prevent or reverse the onset and progression of epilepsy are important goals of clinical and preclinical researches. Based on the current studies, to realize the transformation from anti-seizure to anti-epileptogenesis and disease-modifying therapy, it not only needs standardized animal models and biomarkers that can predict the epileptogenesis or progression but also needs sufficient patients, rigorous design schemes, and cutting-edge analysis methods to successfully transform preclinical research into clinical practice. There is no doubt that in the future, targeting various nerve injury pathways to achieve anti-epileptogenesis and disease-modifying therapy probably becomes a truly effective means of treating and preventing epilepsy.

Anticoncepción en mujeres epilépticas / Contraception in epileptic women

Resumen La elección de un método anticonceptivo considerado como altamente efectivo en mujeres epilépticas en edad fértil es importante, ya que requiere al momento de indicarlos tener en cuenta los criterios de elegibilidad y las posibles interacciones farmacológicas entre determinados tipos de fármacos anticonvulsivantes (principalmente las inductoras enzimáticas del sistema hepático P450 como: carbamacepina, fenitoína, fenobarbital, oxacarbamacepina, eslicarbazepina, rufinamida, lacosamida y topiramato en dosis altas) y ciertos métodos anticonceptivos (anticonceptivos orales combinados o solo con progesterona e implantes de progesterona subdérmicos) pudiendo acelerar el metabolismo de estas últimas con el consiguiente riesgo de fracaso o viceversa, reduciendo la concentración plasmática (como por ejemplo; lamotrigina) predisponiendo a crisis epilépticas, riesgo de embarazos no deseados, abortos, teratogenicidad por valproato, complicaciones materno fetal y dificultad en el manejo de la actividad epiléptica durante la gestación. En caso de asociarse ambas medicaciones, se debe considerar el uso combinado con un método de barrera u optar por la utilización de inyección de depósito de acetato de medroxiprogesterona o dispositivo intrauterino como anticoncepción. Está demostrado que el asesoramiento sobre planificación familiar en la primera consulta puede influenciar en la elección del método anticonceptivo y el inicio temprano de ácido fólico en caso de búsqueda de fertilidad. En conclusión, se debe analizar junto con las pacientes epilépticas las diferentes opciones terapéuticas con el fin de lograr y optimizar la mejor meta de cada uno.

Abstract The choice of a contraceptive method considered highly effective in epileptic women of childbearing age is important, since it requires taking into account the eligibility criteria and the possible pharmacological interactions between certain types of anti-seizure drugs (mainly enzyme inducers drugs of the hepatic system P450 such as: carbamazepine, phenytoin, phenobarbital, oxacarbamazepine, eslicarbazepine, rufinamide, lacosamide and topiramate in high doses) and certain contraceptive methods (oral contraceptives combined or only with progesterone and subdermal progesterone implants), which may accelerate the metabolism of the latter with the consequent risk of failure or vice versa, reduction of plasma concentration (such as lamotrigine) predisposing to seizures, risk of unwanted pregnancies, abortions, teratogenicity due to valproato, maternalfetal complications and difficulty in the management of epileptic activity during pregnancy. In case of prescribing both medications, the combined use with a barrier method should be considered or the use of a depot injection of medroxyprogesterone acetate or intrauterine device as contraception should be considered. Family planning counseling at the first visit has been shown to influence the choice of the contraceptive method and the early initiation of folic acid in the search for fertility. In conclusion, the different therapeutic options should be analyzed together with the epileptic patients in order to achieve and optimize the best goal for each one.

Dental Considerations of a 4-year-old Girl with Lennox-Gastaut Syndrome. Case Report and Literature Review.

We present the developmental, oral, clinical, radiographic findings and oral treatment of a 4-year-old girl presenting with Lennox-Gastaut syndrome (LGS), which is a severe disabling childhood epilepsy disease that is treated with one or multiple anti-epileptic drugs (AEDs). The child was wheel-chair bound, developmentally delayed, gastrostomy tube (G-tube) fed, and suffered from multiple seizures and infantile spasms. The child’s medical history included an under-developed pituitary gland, gastro esophageal reflux disease, vision and hearing impairment, history of chronic aspiration pneumonia, and allergies. Although the oral findings included no carious lesions, heavy calculus accumulation, spontaneous bleeding from the gingiva, generalized gingival hyperplasia (GH) and abnormal increased mobility in several deciduous teeth. This report describes the comprehensive radiographic and clinical examination and the treatment under general anesthesia.