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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.
ABSTRACT
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.
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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.
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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.
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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.
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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.
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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.