Research progress on the effect of new anti-seizure medications on cognitive function / 临床神经病学杂志

Epilepsy is a kind of brain dysfunction syndrome characterized by paroxysmal,transient,repetitive and rigid characteristics caused by abnormal discharge of highly synchronized neurons in the brain.Epilepsy is often accompanied by cognitive dysfunction.At present,anti-seizure medications are the most important methods of clinical treatment.Most of the traditional anti-seizure medications can cause cognitive dysfunction,and the influence of new anti-seizure medications on cognitive function is not completely clear.This paper reviews the influence of new anti-seizure medications on cognitive function and the possible related mechanisms of action based on relevant literature at home and abroad.It is expected that clinicians should pay attention to cognitive function in the process of diagnosis and treatment of epilepsy,and help clinicians realize the influence of anti-seizure medications on cognitive function,and rationally choose anti-seizure medications for patients.

The progress of the application of machine learning in epilepsy / 中华神经科杂志

Epilepsy is an episodic, transient, stereotypic brain dysfunction caused by highly synchronized abnormal neuronal discharges in the brain, with unpredictable timing of seizures, for which the main treatment modalities are antiepileptic drugs and surgery. Its diagnosis and treatment require a large number of aids and clinical experience. For multiple clinical aspects of epilepsy, such as seizure prediction, drug therapy prognosis, and surgical treatment evaluation, machine learning can incorporate multiple clinical and imaging factors through deep mining of data, establish corresponding learning models, improve the efficiency and accuracy of epilepsy diagnosis, realize individualized application of antiepileptic drugs, and improve the preoperative evaluation and prognosis of epilepsy patients.

Effect of application of anti-seizure medications on the development of chronic epilepsy after autoimmune encephalitis / 中华神经科杂志

Objective:To investigate and analyze the use and duration of anti-seizure medications (ASMs) in patients with chronic epilepsy after autoimmune encephalitis (AE), as well as the effect of ASMs use on the formation of this epilepsy to provide relevant evidence for the choice of ASMs in patients with acute seizure or chronic epilepsy after AE.Methods:A retrospective follow-up study was performed on AE patients (including patients with antibody-negative autoimmune limbic encephalitis) diagnosed in the Affiliated Brain Hospital of Nanjing Medical University from December 1, 2013 to October 31, 2022. The dates of the first seizure onset and the chronic epilepsy formation (defined as 1 year after immunotherapy) were recorded. The initial time, types and numbers of ASMs used in acute symptomatic seizure (ASS) and the maintenance time, types and numbers of ASMs in chronic epilepsy period (the continuation or the combined therapy of ASMs) were collected, respectively. A Logistic regression model was used to analyze multi-influencing factors on the formation of chronic epilepsy after AE.Results:A total of 332 patients were enrolled in this study, of whom 32.5% (108/332) with antibody-negative autoimmune limbic encephalitis. In total, 54.8% (182/332) of patients were males, and the age of onset was (40.7±19.7) years. Finally, 81.0% (269/332) of participants manifested ASS, and 57.2% (190/332) developed chronic epilepsy up to the last follow-up. The follow-up time was 1-8 years, with a median of 2 years. All patients received ASMs treatment during ASS period. Among the ASS patients, 48.0% (129/269) were prescribed monotherapy of ASMs, and 52.0% (140/269) were given the combined therapy of ASMs. Of all the patients with ASMs, 70.3% (189/269) were given early ASMs treatment (within 24 hours of the seizure onset), and 29.7% (80/269) were given delayed ASMs treatment. Subsequently, 81.0% (218/269) of the ASS patients continued the ASMs treatment (>6 months), and 19.0% (51/269) stopped use of ASMs. In the chronic epilepsy stage, 79.5% (151/190) of thee epilepsy patients continued ASMs, of whom 37.1% (56/151) were treated with monotherapy, and 62.9% (95/151) were treated with combined therapy. The incidence of chronic epilepsy was 81.3% (65/80) in the delayed ASMs treatment group, higher than the 66.1% (125/189) in the early ASMs treatment group,with statistically significant difference (χ 2=6.189, P=0.013). There were no statistically significant differences in the ASMs types and whether combined therapy of ASMs was used between chronic epilepsy group and non-chronic epilepsy group. The Logistic regression model showed that delayed ASMs treatment ( OR=2.306,95% CI 1.032-6.387, P=0.018), positive anti-neuronal intracellular antibodies ( OR=2.626,95% CI 1.536-9.531, P=0.004,compared with anti- neuronal surface antibodies), abnormal brain magnetic resonance imaging ( OR=9.883,95% CI 3.608-27.071, P<0.001), elevated cerebrospinal fluid protein ( OR=2.874,95% CI 1.115-7.409, P=0.029), and abnormal electroencephalogram ( OR=9.287,95% CI 3.767-22.896, P<0.001) were independent risk factors for chronic epilepsy after AE. Conclusions:The development of chronic epilepsy after AE is associated with the occurrence of ASS and the delayed use of ASMs, but the type of ASMs or whether the combined ASMs therapy is used is not associated with the formation of chronic epilepsy after AE. It is concluded that early ASMs treatment for the AE patients with ASS may reduce the incidence of chronic epilepsy. For AE patients with ASS who have undergone early standardized treatment, long-term, combined ASMs treatment may not be necessary.

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.

Recommendations for prescription review of commonly used anti-seizure medications in treatment of children with epilepsy / 中华实用儿科临床杂志

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Safety and efficacy of oral Lacosamide as an add-on therapy in Chinese children with partial-onset seizures / 中华实用儿科临床杂志

Objective:To evaluate the long-term safety, tolerability and efficacy of Lacosamide add-on therapy in Chinese children with partial-onset seizures.Methods:SP848 was a global multicenter single-arm study involving 60 Chinese children with partial-onset seizures with the age of 4-17 years who were managed by Lacosamide add-on therapy at seven hospitals across China from April 2018 to May 2019.After treatment with at least two kinds of anti-seizure medications simultaneously or sequentially, partial seizures were still poorly controlled and Lacosamide oral solution (syrup) or tablets were added.The minimum initial oral dose was 2 mg/(kg·d), and the maximum allowable dose was 12 mg/(kg·d)or 600 mg/d during the study period.The dose was adjusted according to the tolerance and seizure control level of partial-onset seizures children.Seizure frequency and the median percentage change in partial-onset seizures per 28 days from baseline to the final visit were recorded, including 50% responder rate and 75% responder rate.Results:A total of 60 Chinese children with the mean age of 9.18 (4.00-15.40) years were included in this interim analysis, involving 39 males and 21 females.The mean course of epilepsy was 5.04 (0.50-15.20) years.A total of 43 patients (71.7%) still have been treated.One patient (1.7%) has completed the 6-12 months of follow-up, and 14 patients (23.3%) have completed the follow-up for less than 6 months.The median change in the frequency of partial seizures every 28 days from baseline to the last visit was -2.91, with its median percentage as -25.46%, and the proportions of ≥50%, while ≥75% responder rate were 40.0% and 28.3%, respectively.A total of 52 patients (86.7%) had 265 treatment emergent adverse events (TEAE), 11 patients (18.3%) had 19 serious TEAE, 37 patients (61.7%) had 127 drug-related TEAE, and 11 patients (18.3%) had 16 TEAE leading to the discontinuation of the trial.The most common TEAE were upper respiratory tract infections (20 cases, 33.3%), followed by drowsiness (16 cases, 26.7%), dizziness (15 cases, 25.0%) and vomiting (13 cases, 21.7%). There were no abnormal changes in the electrocardiographic findings during the treatment.Conclusions:For Chinese patients with partial seizures who are older than the age of 4 years and poorly controlled by other drugs, Lacosamide is effective and well tolerated as an add-on therapy drug.The safety characteristics are consistent with those reported in children and adults.No new safety concerns are identified.

Effects of anti-seizure medications on cognitive function / 中华神经科杂志

Epilepsy is a common neurological disease, and studies have shown that some epilepsy patients are combined with cognitive impairment. In clinical practice, it has been found that, in addition to the seizure itself, anti-seizure medications can also have a corresponding impact on the cognitive function of epilepsy patients. However, the effects of some drugs on the cognitive function of epilepsy patients are still inconclusive, and the mechanism of their influence on cognitive function in epilepsy patients is not elucidated. In recent years, some studies followed up the cognitive function of patients receiving anti-seizure medications therapy, and put forward guidance. This article focused on the research of commonly used drugs on cognitive function, the possible mechanism of drugs affecting cognitive function, the rational use of drugs in different groups of people and the prevention strategies of related cognitive dysfunction, hoping to improve emphasis on cognitive function in epilepsy patients and guide clinical practice.

Recent advance in correlation between plateau environment and epilepsy / 中华神经医学杂志

Epilepsy is one of the common neurological diseases in the nervous system. The susceptibility, seizure frequency and drug efficacy in epilepsy vary across different regions, possibly related to living environment and genetic factors. The unique geographical environment and dietary habits of people living on plateaus are associated with occurrence and development of epilepsy to some extent. However, research on the correlation between plateau environment and epilepsy is currently limited. This paper comprehensively reviews the correlation between plateau environment and epilepsy, aiming to better understand the real scenarios and pathogenesis of epilepsy and offer valuable reference for prevention, diagnosis and treatment of epilepsy in plateau areas.

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.

Research progress on epilepsy in the plateau area / 中国神经精神疾病杂志

Epilepsy is a chronic neurological disease and a common disease in neurology.The epidemiologic characters,clinical characteristics and risk factors of epilepsy vary from region to region.Although there are relatively few studies on epilepsy in the plateau,current studies show that its morbidity and prevalence are higher than those in other regions.There is a large gap in epilepsy treatment in the plateau area,and the quality of life of patients is poor.Among them,cerebrovascular diseases,cerebral parasitic diseases and craniocerebral trauma are common causes of epilepsy in the plateau area.This paper summarizes the epidemiologic characteristics,clinical characteristics,risk factors,etiology,comorbidities and other related studies of epilepsy in plateau areas,aiming to offer valuable reference for the diagnosis and treatment of epilepsy patients in plateau areas.

Research progress of drug-withdrawal in patients after epilepsy surgery / 中国神经精神疾病杂志

Epilepsy surgery is an effective treatment of drug-resistant epilepsy.Once patients became seizure free for certain period after epilepsy surgery,whether anti-seizure medications(ASMs)could be withdrawn is the primary concern of clinicians and patients.However,there is no consensus about management of anti-seizure medications in patients after epilepsy surgery.Patients after epilepsy surgery can withdraw ASMs when they become seizure free for 1 to 2 years.The dose reduction is usually done at every 2 to 3 months.For patients receiving multiple ASMs,each one should be individually tapered completely prior to the subsequent medication and the primary medication is always withdrawn in the end.Longer epilepsy duration prior to surgery,older age at surgery,patients with focal cortical dysplasia,incomplete resection of the epileptogenic zone and presence of interictal epileptiform discharges in postoperative EEG may predict the risk of seizure relapse in patients who underwent ASM withdrawal after epilepsy surgery.Patients with seizure relapse on ASM withdrawal generally have benign outcome after reinstitution of medical treatment.

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.