ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Neonatal seizures are often complex and difcult to recognize, but can be identied through electroencephalogram (EEG) monitoring. The Brighton Collaboration has developed a scheme with ve levels of diagnostic certainty to guide treatment decisions when EEG is not available. Different seizure types are usually associated with specic underlying causes, which may require specic diagnostic and treatment approaches. Neonatal seizures require prompt management, including the stabilization of cardiovascular and respiratory function and the identication of the underlying cause. EEG monitoring is considered essential for the detection of seizures and should be performed until the neonate has been seizure-free for 12 to 24 hours. Treatment involves the use of antiseizure medication and may include pyridoxine challenge or other treatment options such as the ketogenic diet, intravenous immunoglobulin, or corticosteroids if seizures are refractory to conventional antiseizure medication. It is important to differentiate between seizures and nonepileptic motor phenomena, which can occur without obvious cause or as symptoms of drug withdrawal, electrolyte abnormalities, hypoglycemia, or infection. Neuroimaging is also considered essential for the detection of possible structural abnormalities in neonates with seizures.
ABSTRACT
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.
ABSTRACT
Progressive myoclonic epilepsies (PMEs) are a group of rare genetic diseases. Common clinical manifestations include action myoclonus often with generalized tonic-clonic seizures, cognitive impairment and other focal neurological deficits. PMEs generally respond poorly to antiseizure drugs and have a poor overall prognosis. Disorders that can cause PMEs include Unverricht-Lundborg disease, Lafora disease, neuronal ceroid lipofuscinosis, myoclonic epilepsy with fragmented red fiber syndrome, sialic acidosis, dentate erythronucleus pallidus Lewy body atrophy, etc. The current treatments for PMEs include drug therapy, neuromodulatory therapy, dietary therapy, anti-inflammatory and immunomodulatory therapy, enzyme replacement therapy and gene therapy. This article reviews the currently known treatments for PMEs, and provides ideas for better research and exploration of treatments for PMEs.
ABSTRACT
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.
ABSTRACT
Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.
Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.
Subject(s)
Animals , Rabbits , Substance Withdrawal Syndrome/drug therapy , Oils, Volatile , Pentylenetetrazole/toxicity , Pentylenetetrazole/therapeutic use , Seizures/chemically induced , Seizures/drug therapy , Morphine/therapeutic use , Anticonvulsants/therapeutic useABSTRACT
ABSTRACT Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.
RESUMO Introdução: A epilepsia afeta cerca de 50 milhões de pessoas em todo o mundo e aproximadamente 30% desses pacientes apresentam epilepsia refratária, com possíveis consequências na qualidade de vida, morbidade e mortalidade prematura. Objetivo: O objetivo do tratamento com fármacos antiepilépticos (FAEs) é permitir que os pacientes permaneçam sem crises epilépticas com boa tolerabilidade. O levetiracetam (LEV) é um FAE de amplo espectro, com mecanismo de ação único, diferente dos demais e que demonstra ser eficaz e seguro no tratamento de adultos e crianças. Métodos: Estudo de fase III, multicêntrico, randomizado, duplo-cego e controlado por placebo avalia a eficácia e a segurança do LEV em crianças e adultos (4-65 anos) como tratamento adjuvante para crises de início focal em 114 pacientes já tratados com até três FAEs. A análise de eficácia primária foi baseada na proporção de pacientes que apresentaram redução ≥50% no número médio de crises epilépticas focais semanais, durante 16 semanas. Os pacientes foram randomizados para receber placebo ou LEV, titulado a cada duas semanas de 20 mg/kg/dia ou 1.000 mg/dia até 60 mg/kg/dia ou 3.000 mg/dia. Resultados: LEV foi significativamente superior ao placebo (p=0,0031), com 38,7% dos participantes no grupo LEV e 14,3% no grupo controle que apresentaram redução das crises focais. LEV apresenta bom perfil de segurança com eventos adversos semelhantes ao placebo. Conclusão: Corroborando com os resultados da literatura, o levetiracetam mostra-se eficaz e seguro para crianças e adultos com epilepsia focal refratária.
Subject(s)
Humans , Child , Adult , Epilepsies, Partial , Drug Resistant Epilepsy , Quality of Life , Double-Blind Method , Treatment Outcome , Drug Therapy, Combination , Levetiracetam/therapeutic use , Anticonvulsants/therapeutic useABSTRACT
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.
Subject(s)
Humans , Female , Pregnancy , Contraception , Epilepsy/drug therapy , Seizures/drug therapy , Anticonvulsants/adverse effectsABSTRACT
Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.
Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.
ABSTRACT
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.