Efficacy of Personalized Postoperative Epilepsy Management in Patients with Glioblastoma Utilizing IDH1 Gene Assessment.

Objective: We explored the correlation between the presence of isocitrate dehydrogenase-1 (IDH1) mutations and the incidence of postoperative epilepsy in patients with glioblastoma, as well as assessed the efficacy of preemptive administration of antiepileptic medications in mitigating the occurrence of postoperative epilepsy. Methods: Fifty-three patients who received a postoperative pathological diagnosis of glioblastoma, were enrolled in this study. Tumor specimens were subjected to IDH1 gene analysis. The patient cohort was stratified based on their IDH1 mutation status and the administration of prophylactic antiepileptic drugs during the postoperative phase. We subsequently conducted a comparative analysis of postoperative epileptic complications within each patient subgroup. Results: In the cohort of 53 patients under study, the occurrence of epilepsy was observed in 10 out of 21 patients carrying IDH1 mutations, while 5 out of 32 patients with wild-type IDH1 also experienced epilepsy, revealing a statistically significant difference (P < 0.05). Among the 27 patients who received prophylactic antiepileptic drugs, 6 of them developed epilepsy, whereas 9 out of 26 patients who did not receive prophylactic antiepileptic drugs exhibited concurrent epilepsy, with no statistically significant difference (P > 0.05). However, when performing a subgroup analysis, it was found that 3 out of 12 patients with IDH1 mutations who received prophylactic antiepileptic drugs experienced epilepsy, whereas 7 out of 9 patients who did not receive prophylactic antiepileptic drugs developed epilepsy, demonstrating a statistically significant difference (P < 0.05). Furthermore, within the group of 15 patients with wild-type IDH1, 3 patients who received prophylactic antiepileptic drugs developed epilepsy, while 2 cases of epilepsy occurred among the 17 patients who did not receive prophylactic antiepileptic drugs, with no statistically significant difference (P > 0.05). Conclusion: In individuals with IDH1 mutant glioblastoma who have undergone surgical resection, the implementation of preventive antiepileptic therapy demonstrates a potential to diminish the occurrence of postoperative epilepsy.

Challenges and prospects in geriatric epilepsy treatment: the role of the blood-brain barrier in pharmacotherapy and drug delivery.

The blood-brain barrier (BBB) is pivotal in maintaining neuronal physiology within the brain. This review delves into the alterations of the BBB specifically in the context of geriatric epilepsy. We examine how age-related changes in the BBB contribute to the pathogenesis of epilepsy in the elderly and present significant challenges in pharmacotherapy. Subsequently, we evaluate recent advancements in drug delivery methods targeting the BBB, as well as alternative approaches that could bypass the BBB's restrictive nature. We particularly highlight the use of neurotropic viruses and various synthetic nanoparticles that have been investigated for delivering a range of antiepileptic drugs. Additionally, the advantage and limitation of these diverse delivery methods are discussed. Finally, we analyze the potential efficacy of different drug delivery approaches in the treatment of geriatric epilepsy, aiming to provide insights into more effective management of this condition in the elderly population.

Clinical characteristics and drug efficacy evaluation of voltage-gated potassium channel-related genetic epilepsy / 中国药理学通报

Aim To analyze the genotype-phenotype characteristics of voltage-gated potassium channels (Kv) associated genetic epilepsy and evaluate the efficacy of anti-seizure medications(ASMs). Methods PubMed database was searched and patients meeting the inclusion criteria were included for analysis. We divided the patients into “benign”, “encephalopathic” and other phenotypes according to the clinical characteristics. We performed descriptive statistical analysis of patients' mutated genes, clinical phenotype and drug efficacy, and used logistic regression to explore the influencing factors of treatment outcome. Results Data of 474 children were included for analysis. There were significant differences among different phenotypes in mutated genes, source of mutations and so on. In terms of clinical characteristics, there were also significant differences between patients with different phenotypes in age of onset, combined developmental delay and so on. In terms of monotherapy, phenobarbital was the most common treatment choice for children with “benign” phenotype, and sodium channel blockers (SCBs) were the most common treatment choice for children with “encephalopathy” phenotype, and the efficacy of SCBs monotherapy was superior to that of other ASMs. Multivariate Logistic analysis of the children receiving monotherapy showed that whether the children were combined with developmental delay and whether SCBs were used were significant factors influencing the efficacy of drug therapy. Conclusions Patients with the “benign” and “encephalopathic” phenotypes differ in several aspects of genetic variation, clinical characteristics, and drug selection. These results suggest that SCBs may be one of the recommended options for monotherapy.

The Value of Shunt Surgery or Prophylactic Antiepileptic Therapy or Both in the Development of Dementia at Early Stages in Patients With Ventricular Dilatation.

The primary purpose of the current study was to determine the value of the shunt surgery and/or prophylactic antiepileptic therapy, in patients after mild traumatic brain injury (mTBI) with ventricular dilatation (VD) and incipient cognitive impairment, in the prevention of cognitive deterioration and probably in the development of dementia. Based on the following criteria: a) mTBI b) VD detected in CT scan during admission, and c) the presence of one of the following: i) dizziness, ii) headache, and iii) seizures, admitted to the Emergency Department between January 2010 and January 2020, we enrolled 127 of 947 eligible subjects. The subjects were divided into five groups: Group A (control group): only VD illustration in CT scan, Group B: incipient dementia, who had a more insidious onset presenting with cognitive dysfunctions at indefinite ages, Group C: shunt system (SH)/antiepileptic drugs (AEDs) presenting with cognitive dysfunction and urinary incontinence or gait disturbances or both, that were treated as idiopathic normal-pressure hydrocephalus (iNPH) with the surgical placement of an SH and AED therapy (standard AED phenytoin (1000 mg loading dose followed by 300 mg) daily), and Group D: AED, presenting with cognitive dysfunctions at indefinite ages and one or two episodes of seizures in the past, treated with AED from the very first moment of initiation with a standard AED phenytoin (1000 mg loading dose followed by 300 mg) daily. Overall, improvement in daily activities was achieved in 14.1% (18 of 127 patients), recording a significantly higher performance in group D (5.5%) rather than in groups A (1.5%), B (3.1%), and C (3.9%), (p < 0.05). We concluded that changes in VD (ΔVD) were associated with improvement in mRS (ΔmRS ≥ 1) - daily activities and mental status. ΔVD was also independently associated with reduced daily activities during the long-term follow-up. Interestingly, therapeutic shunting and AED in patients with a history of epilepsies may have a positive impact on the development of mental status impairment. This is a novel observation that has to be confirmed by more extensive multicenter studies in the future.

Evidence-Based Recommendations for Seizure Prophylaxis in Patients with Brain Metastases Undergoing Stereotactic Radiosurgery.

Symptomatic epilepsy is frequently encountered in patients with brain metastases (BM), affecting up to 25% of them. However, it generally remains unknown whether the risk of seizures in such cases is affected by stereotactic radiosurgery (SRS), which involves highly conformal delivery of high-dose irradiation to the tumor with a minimal effect on adjacent brain tissue. Thus, the role of prophylactic administration of antiepileptic drugs (AED) after SRS remains controversial. A comprehensive review and analysis of the available literature reveals that according to prospective studies, the incidence of seizures after SRS for BM varies from 8% to 22%, and there is no evidence that SRS increases the incidence of symptomatic epilepsy. Therefore, routine prophylactic administration of AED prior to, during, or after SRS in the absence of a seizure history is not recommended. Nevertheless, short-course administration of an AED may be judiciously considered (on the basis of class III evidence) for selected high-risk individuals.

[The effectiveness of antiepileptic therapy in patients with epileptic syndromes associated with myoclonic seizures]. / Effektivnost' protivoepilepticheskoi terapii u patsientov s epilepticheskimi sindromami, assotsiirovannymi s mioklonicheskimi pristupami.

OBJECTIVE: To evaluate the effectiveness of antiepileptic therapy of epileptic syndromes associated with myoclonic seizures. MATERIAL AND METHODS: One hundred and three patients with epilepsy, in whom myoclonic seizures were identified during the observation, were examined. The observed myoclonic seizures entered the structure of 11 different epileptic syndromes. RESULTS AND CONCLUSION: Drug remission is achieved in 67% of patients, a decrease in the frequency of seizures by 50% or more was noted in 23,3%, the lack of effect in 9,7%. The effectiveness of antiepileptic therapy was significantly different in different groups of epileptic syndromes. The high effectiveness of antiepileptic therapy in the general group of patients in this study is mainly due to the prevalence of patients with juvenile myoclonic epilepsy, in which the highest percentage of remission was observed.

Gelastic seizures not associated with hypothalamic hamartoma: A long-term follow-up study.

OBJECTIVE: The objective of the study was to describe the electroclinical features, seizure semiology, and the long-term evolution of gelastic seizures (GS) not associated with hypothalamic hamartoma (HH). METHODS: We reviewed video-electroencephalogram (video-EEG) recordings from pediatric patients with GS without HH admitted to 14 Italian epilepsy centers from 1994 to 2013. We collected information about age at onset, seizures semiology, EEG and magnetic resonance imaging (MRI) findings, treatment, and clinical outcome in terms of seizure control after a long-term follow-up. RESULTS: A total of 30 pediatric patients were stratified into two groups according to neuroimaging findings: group 1 including 19 children (63.3%) with unremarkable neuroimaging and group 2 including 11 children with structural brain abnormalities (36.7%). At the follow-up, patients of group 1 showed better clinical outcome both in terms of seizure control and use of AED polytherapy. Our patients showed remarkable clinical heterogeneity, including seizure semiology and epilepsy severity. Electroencephalogram recordings showed abnormalities mainly in the frontal, temporal, and frontotemporal regions without relevant differences between the two groups. Overall, carbamazepine showed good efficacy to control GS. CONCLUSIONS: Patients with nonlesional GS have a more favorable outcome with better drug response, less need of polytherapy, and good long-term prognosis, both in terms of seizure control and EEG findings.

Prevention, Treatment, and Monitoring of Seizures in the Intensive Care Unit.

The diagnosis and management of seizures in the critically ill patient can sometimes present a unique challenge for practitioners due to lack of exposure and complex patient comorbidities. The reported incidence varies between 8% and 34% of critically ill patients, with many patients often showing no overt clinical signs of seizures. Outcomes in patients with unidentified seizure activity tend to be poor, and mortality significantly increases in those who have seizure activity longer than 30 min. Prompt diagnosis and provision of medical therapy are crucial in order to attain successful seizure termination and prevent poor outcomes. In this article, we review the epidemiology and pathophysiology of seizures in the critically ill, various seizure monitoring modalities, and recommended medical therapy.

Clinical and genetic analysis of Chinese patients with KCNQ2 mutation-induced neonatal/infantile epileptic disorders / 中华实用儿科临床杂志

Objective@#To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation.@*Methods@#Twenty-two patients were collected in the Department of Pediatrics, Peking University First Hospital from April 2007 to July 2016.The phenotype-genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 mutation was identified by the targeted next generation sequencing.@*Results@#Twenty-two de novo KCNQ2 missense mutations from 22 patients with neonatal/infantile epileptic disorders were found.These patients had an onset of epilepsy in early infancy (median age: 2 days). The seizure type of the first onset was mainly focal seizure.Atypical absence epilepsy, a novel phenotype of KCNQ2 mutation-induced epilepsies was found.The mortality of these patients was high, as 5 patients of the 22 patients died in the follow-up period, 4 of which might result from sudden unexpected death in epilepsy.In the 22 patients, 8 patients with anti-epileptic monotherapy became seizure-free.Of the 8 patients with a monotherapy, 3 patients were treated with valproic acid and no clinical onset was observed.@*Conclusions@#This study expands the phenotype of KCNQ2-related epileptic disorders.These patients have high mortality.Valproate acid is the potentially effective monotherapy for these patients.

The pharmacological management of Lennox-Gastaut syndrome and critical literature review.

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with a prevalence of 1-2% of all patients with epilepsy. It is characterized by multiple pharmaco-resistant seizure types, including tonic, atypical absences and tonic or atonic drop attacks, and the presence of electroencephalographic abnormalities, such as slow-spike waves and paroxysmal fast rhythms. Intellectual disability, behavioural and psychiatric disorders are common comorbidities; these disturbances have a multi-factorial pathogenesis. The selection of the most appropriate drug must be tailored to each patient and guided by the prevalent seizure type. In this paper available pharmacological options are discussed and for each pharmacological agent, current evidence of efficacy and tolerability is provided. Valproic acid represents one of the first-line options in the treatment of LGS. Anyway, other antiepileptic drugs (AEDs) may be considered and added: lamotrigine, rufinamide, topiramate, clobazam can be efficacious. The use of felbamate must be carefully evaluated because of its adverse events. Perampanel, zonisamide, levetiracetam and fenfluramine have shown to be useful in the treatment of selected patients; nevertheless, the lack of RCTs does not allow to recommend their use in a systematic way. Recently, cannabidiol has provided high evidence of efficacy against LGS seizures; however, these data must be confirmed by long-term extensive studies and by trials comparing different AEDs, one to each other.

Development of outcome criteria to measure effectiveness of antiepileptic therapy in children.

PURPOSE: Clinical trials of antiepileptic drugs frequently measure outcomes of seizure control, which demonstrate efficacy. Yet, functional status, quality of life, and long-term treatment effects reflecting effectiveness are scarcely assessed. We sought to use a consensus method to help identify which outcome criteria key stakeholders consider should be used to measure effectiveness in trials of antiepileptic treatments for children. METHOD: A two-round Delphi survey was used; parents of children with epilepsy and local, international experts comprising academics and clinicians participated in the survey. In the first round, 32 experts, 50 parents, and 15 children with epilepsy aged >13years suggested outcomes that they considered important in determining effectiveness of antiepileptic therapy in children, separately for preschool and school age. In the second round, 29 experts and 42 parents scored the importance of outcomes from the list suggested by at least 10% of round 1 respondents and also proposed five most important outcomes. RESULTS: Complete seizure freedom (67%), seizure frequency (48%), ability to perform normal day-to-day activities (45%), and quality of life (40%) were identified as the most important outcomes of antiepileptic therapy in children of both age groups. Additionally, effect on developmental milestones (47%) and child's compliance to treatment regimen (39%) were identified as most important in preschool age group and school performance (49%); adverse effects (39%) were identified as most important in school age group. CONCLUSION: For the first time, this study has identified outcome priorities regarding antiepileptic treatment in children based on the key stakeholders' perspectives. It could be used as a provisional list of outcomes for inclusion in a core outcome set for children with epilepsy.

Prophylactic Antiepileptic Drug Use in Patients with Brain Tumors Undergoing Craniotomy.

BACKGROUND: Prophylactic use of antiepileptic drugs (AEDs) for patients undergoing brain tumor surgery is common practice despite lack of clear evidence. We hypothesized that prophylactic AED (pAED) use did not affect seizure rates in patients with brain tumor who underwent craniotomy for tumor resection. METHODS: A retrospective review was performed of 606 patients who underwent surgery for brain tumors from 2006 to 2013 at the University of Florida, excluding patients with preexisting seizure condition before tumor diagnosis. Data were analyzed to determine seizure incidence, AED use, and AED toxicities. RESULTS: Most patients (81%) had no seizure on presentation. Eight patients did not present with seizure but had seizure postoperatively, and 9 patients did not present with seizure or have seizure postoperatively but did have seizure on follow-up. Despite not presenting with a seizure preoperatively, 208 patients (43%) were placed on pAED preoperatively, 313 patients (64%) were on AED in the postoperative period, and 274 patients (56%) remained on AED at discharge. The pAED use odds ratio for seizures was 1.3 (95% confidence interval, 0.5-3.4; P = 0.599). At last follow-up, 34% of patients with no seizure on presentation remained on pAEDs. CONCLUSIONS: pAEDs did not significantly reduce postoperative seizures in patients with brain tumor in this analysis. In addition, pAED was often continued once prescribed even if the patient remained seizure free.

Guiding Antiepileptic Therapy in a Pediatric Patient with Severe Meningoencephalitis and Decompressive Craniectomy with the Use of Amplitude-Integrated Electroencephalography.

Introduction Amplitude-integrated electroencephalography (aEEG) is one of the most widely used neuromonitoring tools in neonatology today. However, little is known about its clinical indications and potential benefits in pediatric intensive care patients. Based on limited experience, its impact on therapeutic decision-making in this patient population is unclear. Case Description We report the case of a 16-year-old boy who, after a pansinusitis, developed a severe meningoencephalitis and intracranial empyema with increased intracranial pressure that required drainage and decompressive craniectomy. He subsequently developed status epilepticus despite a combination of various anticonvulsants. Only after the initialization of an aEEG, we were able to adequately diagnose and continuously monitor his seizure activity and titrate the effect of the antiepileptic drugs. During his hospital stay, we were able to clearly monitor and guide our therapy by accurately identifying the termination of status epilepticus and the recurrence of seizures. Discussion With the help of aEEG, it was easy to identify the nonconvulsive status epilepticus (NCSE) and the ongoing seizure activity in this teenage patient. NCSE is a clinical problem with an effect on the outcome of the patient and is often underdiagnosed. AEEG enabled a rapid detection and management of seizure activity and thereby reduced the overall seizure burden, which was associated with better neurologic outcome.

The KCC2 Cotransporter and Human Epilepsy: Getting Excited About Inhibition.

The cation-Cl- cotransporter KCC2, encoded by SLC12A5, is required for the emergence and maintenance of GABAergic fast synaptic inhibition in organisms across evolution. These findings have suggested that KCC2 deficiency might play a role in the pathogenesis human epilepsy, but this has only recently been substantiated by two lines of genetic evidence. The first is the discovery of heterozygous missense polymorphisms in SLC12A5, causing decreased KCC2-dependent Cl- extrusion capacity, in an Australian family with inherited febrile seizures and in a French-Canadian cohort with severe genetic generalized epilepsy (GGE). The second is the discovery of recessive loss-of-function mutations in SLC12A5 in patients with a severe, early-onset Mendelian disease termed "epilepsy of infancy with migrating focal seizures" (EIMFS). These findings collectively support the paradigm that precisely regulated KCC2 activity is required for synaptic inhibition in humans, and that genetically encoded impairment of KCC2 function, due to effects on gene dosage, intrinsic activity, or extrinsic regulation, can influence epilepsy phenotypes in patients. Accordingly, KCC2 could be a target for a novel antiepileptic strategies that aims to restore GABA inhibition by facilitating Cl- extrusion. Such drugs could have relevance for pharmaco-resistant epilepsies and possibly other diseases characterized by synaptic hyperexcitability, such as the spectrum autism disorders.

Clinical dissection of childhood occipital epilepsy of Gastaut and prognostic implication.

BACKGROUND AND PURPOSE: Our aim was to describe the clinical and electrical features and the long-term evolution of childhood occipital epilepsy of Gastaut (COE-G) in a cohort of patients and to compare long-term prognosis between patients with and without other epileptic syndromes. METHODS: This was a retrospective analysis of the long-term outcome of epilepsy in 129 patients with COE-G who were referred to 23 Italian epilepsy centres and one in Austria between 1991 and 2004. Patients were evaluated clinically and with electroencephalograms for 10.1-23.0 years. The following clinical characteristics were evaluated: gender, patient age at seizure onset, history of febrile seizures and migraine, family history of epilepsy, duration and seizure manifestations, circadian distribution and frequency of seizures, history of medications including the number of drugs, therapeutic response and final outcome. RESULTS: Visual hallucinations were the first symptom in 62% and the only manifestation in 38.8% of patients. Patients were subdivided into two groups: group A with isolated COE-G; group B with other epileptic syndromes associated with COE-G. The most significant (P < 0.05) difference concerned antiepileptic therapy: in group A, 45 children responded to monotherapy; in group B only 15 children responded to monotherapy. At the end of follow-up, the percentage of seizure-free patients was significantly higher in group A than in group B. CONCLUSIONS: Childhood occipital epilepsy of Gastaut has an overall favourable prognosis and a good response to antiepileptic therapy with resolution of seizures and of electroencephalogram abnormalities. The association of typical COE-G symptoms with other types of seizure could be related to a poor epilepsy outcome.

Greater Calcium Intake is Associated with Better Bone Health Measured by Quantitative Ultrasound of the Phalanges in Pediatric Patients Treated with Anticonvulsant Drugs.

We aimed to investigate and compare the effects of chronic antiepileptic therapy on bone health in pediatric patients using quantitative ultrasound of the phalanges (QUS) and controlling for potential confounding factors, particularly nutrient intake. The amplitude-dependent speed of sound (Ad-SoS) was measured in 33 epileptic children and 32 healthy children aged 6.5 ± 3.1 and 6.3 ± 1.1 (mean ± SD) years, respectively. There were no significant differences in the demographics such as age, weight and height between epileptic children and the control group children. None of the children in the epileptic or the treatment group were found to have a vitamin D deficiency. There were no significant differences in laboratory tests between groups. Lower QUS figures were found in the epileptic children (p = 0.001). After further adjustment for potential confounders such age, height, weight, calcium intake, vitamin D intake, physical activity and sex, the differences remained significant (p < 0.001). After further classification of the participants based on the tertile of calcium intake, no significant differences were found between patients and healthy controls in the greatest tertile of calcium intake (p = 0.217). We conclude that anticonvulsant therapy using valproate may lead to low bone mass in children and that an adequate intake of calcium might counteract such deleterious effects.

Seizures in Alzheimer's disease.

Alzheimer's disease (AD) increases the risk for late-onset seizures and neuronal network abnormalities. An elevated co-occurrence of AD and seizures has been established in the more prevalent sporadic form of AD. Recent evidence suggests that nonconvulsive network abnormalities, including seizures and other electroencephalographic abnormalities, may be more commonly found in patients than previously thought. Patients with familial AD are at an even greater risk for seizures, which have been found in patients with mutations in PSEN1, PSEN2, or APP, as well as with APP duplication. This review also provides an overview of seizure and electroencephalography studies in AD mouse models. The amyloid-ß (Aß) peptide has been identified as a possible link between AD and seizures, and while Aß is known to affect neuronal activity, the full-length amyloid precursor protein (APP) and other APP cleavage products may be important for the development and maintenance of cortical network hyperexcitability. Nonconvulsive epileptiform activity, such as seizures or network abnormalities that are shorter in duration but may occur with higher frequency, may contribute to cognitive impairments characteristic of AD, such as amnestic wandering. Finally, the review discusses recent studies using antiepileptic drugs to rescue cognitive deficits in AD mouse models and human patients. Understanding the mechanistic link between epileptiform activity and AD is a research area of growing interest. Further understanding of the connection between neuronal hyperexcitability and Alzheimer's as well as the potential role of epileptiform activity in the progression of AD will be beneficial for improving treatment strategies.

Follow-up of antiepileptic drug discontinuation after seizure remission in patients with tuberous sclerosis-induced epilepsy / 第二军医大学学报

Objective: To study the clinical characteristics of antiepileptic drug discontinuation after seizure remission in patients with tuberous sclerosis (TS)-induced epilepsy. Methods: Of 98 epilepsy patients with TS,15 with seizure remission and subsequent antiepileptic drug discontinuation were followed up. The relapse rates of seizures and the retreatments were observed. The causes of seizure relapse were analyzed. Results :Ten(66. 7%) patients had sustained seizure remissions and 5 (33. 3%) had relapses in 15 patients after a mean follow-up of 5 years. Antiepileptic drugs was restarted in the 5 relapsed cases and were successful in a girl, leaving a total sustained remission rate of 73. 3% (11/15) and an absolute relapse rate of 26. 7% (4/15). The relapse was associated with abnormal electroencephalogram, multiple cerebral lesions and biological changes of puberty. Conclusion:The relapse rate of TS epilepsy is similar to the relapse rate of other epilepsies. Reasonable discontinuation of antiepileptic drugs should be considered in the patients who attained seizure remission.