For some patients with drug-resistant focal epilepsy, we usually select conventional surgical resection, which has brought better outcomes. However, others are not eligible for a conventional open surgical resection o...For some patients with drug-resistant focal epilepsy, we usually select conventional surgical resection, which has brought better outcomes. However, others are not eligible for a conventional open surgical resection of the epileptogenic zone because of the proximity of a functional area or the implication of a larger epileptogenic network. Initially, stereoelectroencephalography(SEEG) exploration was a method of electroencephalography recording that was used in the presurgical evaluation of epileptic patients with complex epilepsy. Later, intracerebral electrodes used for SEEG were applied to produce radio frequency thermocoagulation(RF-TC) in epileptic patients. SEEG-guided RF-TC has produced some promising results, especially in the last dacade. Now, it has become popular as a palliative treatment to reduce seizure frequency in patients with drug-resistant focal epilepsy. This article presents a review of SEEG-guided RF-TC.展开更多
Background:Pentylenetetrazole kindling has long been used for the screening of investigational antiseizure drugs.The presence of lamotrigine,at a very low dose,does not hamper kindling in mice;rather it modifies this ...Background:Pentylenetetrazole kindling has long been used for the screening of investigational antiseizure drugs.The presence of lamotrigine,at a very low dose,does not hamper kindling in mice;rather it modifies this epileptogenesis process into drug-resistant epilepsy.The lamotrigine-pentylenetetrazole kindled mice show resistance to lamotrigine,phenytoin,and carbamazepine.It may also be possible that other licensed antiseizure drugs,like the mentioned drugs,remain ineffective in this model;therefore,this was the subject of this study.Methods:Swiss albino mice were kindled with pentylenetetrazole for 35 days in the presence of either methylcellulose vehicle or lamotrigine(subtherapeutic dose,ie,5 mg/kg).Vehicle vs lamotrigine-kindled mice were compared in terms of(a)resistance/response toward nine antiseizure drugs applied as monotherapies and two drug combinations;(b)lamotrigine bioavailability in blood and brain;(c)blood-brain barrier integrity;and(d)amino acids and monoamines in the cerebral cortex and hippocampus.Results:Lamotrigine vs vehicle-kindled mice are similar(or not significantly different P>.05 from each other)in terms of(a)response toward drug combinations;(b)lamotrigine bioavailability;and(c)blood-brain barrier integrity except for,significantly(P<.05)reduced taurine and increased glutamate in the cerebral cortex and hippocampus.Aside from these,lamotrigine-kindled mice show significant(P<.05)resistant to lamotrigine(15 mg/kg),levetiracetam(40 mg/kg);carbamazepine(40 mg/kg),zonisamide(100 mg/kg),gabapentin(224 mg/kg),pregabalin(30 mg/kg),phenytoin(35 mg/kg),and topiramate(300 mg/kg).Conclusion:Lamotrigine-pentylenetetrazole kindling takes longer to develop(~5 weeks)in comparison to lamotrigine-amygdale(~4 weeks)and lamotriginecorneal(~2 weeks)kindling models.However,drug screening through this model may yield superior drugs with novel antiseizure mechanisms.展开更多
Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target no...Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.展开更多
BACKGROUND Perampanel(PER),a third-generation antiepileptic drug,is a selective and noncompetitiveα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist,and has been approved for the treatment of ad...BACKGROUND Perampanel(PER),a third-generation antiepileptic drug,is a selective and noncompetitiveα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist,and has been approved for the treatment of adults and adolescents with focal epilepsy.However,there are only a few studies about the efficacy and tolerability of PER in young children with multidrug-resistant epilepsy.In this case,we aimed to share our clinical experience in this group.CASE SUMMARY A 4-year-old boy without perinatal asphyxia and familial history of epilepsy began to have ictal seizures from age 14 mo,with jerky movement of four limbs and head nodding.Abnormal multifocal discharge and background activity were recorded through electroencephalography,and no pathogenic mutation was found in the whole exome sequencing for the patient and his parents.He had received valproate,levetiracetam,topiramate,oxcarbazepine,clonazepam and lacosamide sequentially at different times,but he still had frequent seizures even after vagus nerve stimulation(VNS)implantation.He was diagnosed with idiopathic multidrug-resistant epilepsy.However,his seizure frequency was significantly reduced after PER administration in a dose-dependent manner,and better cognitive behavior was observed.In addition,the adverse reactions of anger and aggression also appeared.CONCLUSION PER is effective as add-on therapy for young children with multidrug-resistant epilepsy who have previously undergone VNS implantation.展开更多
Background: Drug-resistant epilepsy can be defined as the existence of seizures within 6 months, despite adequate therapy regimens with one or more antiepileptic drugs. Epilepsy surgery has been the standard therapy t...Background: Drug-resistant epilepsy can be defined as the existence of seizures within 6 months, despite adequate therapy regimens with one or more antiepileptic drugs. Epilepsy surgery has been the standard therapy to help those patients who suffer from drug-resistant epilepsy. The goal of this surgery is to halt or reduce the intensity of seizures. This literature review aims to provide an overview of existing surgical procedures for the treatment of drug-resistant epilepsy and the degree of seizure control they provide based on available literature. Methods: Data were collected from medical journal databases, aggregators, and individual publications. The most used databases were PubMed, Medline and NCBI. Some of the keywords used to search these databases include: “drug resistant epilepsy”, “seizure control”, and “neurosurgery”. Results: Epileptic surgery is divided into resective and non-resective procedures. Studies have shown that a full resection of the epileptogenic brain area increases the probability of seizure eradication, however, the risks of postoperative impairments grow as the resection area is extended. On the other hand, patients who are unsuitable for seizure focus removal by resective surgery, such as those with multifocal seizures or overlapping epileptogenic zone with a functional cortex, may benefit from non-resective surgical options such as Vagus Nerve Stimulation and Responsive Neurostimulation. Conclusion: This literature review discusses the comprehensive treatment of epilepsy, especially the surgical treatment of drug-resistant epilepsy. The reviewed studies have shown that epilepsy surgery has promising outcomes in achieving seizure freedom/reducing seizure frequency with minimal adverse effects when performed correctly with the appropriate choice of surgical candidates.展开更多
One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a tradi...One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.展开更多
There have been many advances in the diagnosis and management of focal epilepsies particularly with neuroimaging techniques and magnetic resonance imaging(MRI).Special MRI sequences can be employed to localize and res...There have been many advances in the diagnosis and management of focal epilepsies particularly with neuroimaging techniques and magnetic resonance imaging(MRI).Special MRI sequences can be employed to localize and resect the epileptogenic lesions responsible for focal epilepsy.This study aims to show the benefit of dedicated epilepsy MRI sequences in the diagnosis of focal epilepsies.A general electric 1.5 Tesla MRI machine was used with standard and special sequences.Also,a Nihon Kohden electroencephalography(EEG)machine was used.This is a prospective observational study that included 51 patients with focal epilepsies who had an initial negative brain imaging.They underwent epilepsy MRI sequences along with a prolonged video EEG monitoring to localize the lesion,and then results were analyzed statistically using SPSS 22 program.The majority of patients were males(62.75%)with a mean age of 30 years.The grand majority of patients(74.5%,p value of 0.001)had their lesion localized by the epilepsy MRI.The most commonly found pathology was mesial temporal sclerosis.A significant number of patients(23.5%)were sent for an epilepsy surgery(p value 0.002).This study shows the significant impact of dedicated epilepsy MRI sequences on the diagnosis and management of focal epilepsy in the Lebanese population.展开更多
Background Medium-chain triglyceride ketogenic diet(MCTKD)is previously less commonly used in China.This study was aimed to assess the efficacy and safety of the modified MCTKD in the treatment of drug-resistant epile...Background Medium-chain triglyceride ketogenic diet(MCTKD)is previously less commonly used in China.This study was aimed to assess the efficacy and safety of the modified MCTKD in the treatment of drug-resistant epilepsy in Chinese patients.Methods Patients with drug-resistant epilepsy were enrolled to receive treatment with modified MCTKD in Guangdong Sanjiu Brain Hospital during December 2020 and September 2022.The modified MCTKD contained fat that provided 50–70%of the total energy,as well as proteins and carbohydrates that provided 20–30%and 20%of energy,respectively.The fat component was composed of 20–30%medium-chain triglycerides(MCTs)and 30–40%long-chain triglycerides.The efficacy and safety of the diet were assessed at 1,3 and 6 months.Results A total of 123 patients aged 2.5 to 65 years,were included in this study.The response rates at 1,3 and 6 months were 49.6%,43.1%,and 30.9%,respectively.The seizure freedom rates at 1,3 and 6 months were 12.2%,10.6%,and 6.5%,respectively.The retention rates at 1,3 and 6 months were 98.4%,65.0%and 33.3%respectively.Side effects occurred in 21.14%of patients,which were predominantly gastrointestinal symptoms such as abdominal pain,diarrhea,vomiting,and constipation,and most of them resolved after dietary adjustments.A total of 82 patients(66.7%)discontinued the treatment with the reason of refusing to eat(8.1%),poor efficacy(35.0%),poor compliance(4.9%),and inability to follow-up(9.8%).Only 4 patients(3.3%)withdrew the diet due to side effects.Conclusions The modified MCTKD with MCTs providing 20–30%of energy has a good safety in patients with drug-resistant epilepsy,but its effectiveness needs to be enhanced.Further modifications of MCTKD with an optimal energy ratio are required to achieve a better efficacy and safety.展开更多
BACKGROUND Neurosurgical treatment of severe bilateral occipital lobe epilepsy usually involves two operations several mos apart.AIM To evaluate surgical resection of bilateral occipital lobe lesions during a single o...BACKGROUND Neurosurgical treatment of severe bilateral occipital lobe epilepsy usually involves two operations several mos apart.AIM To evaluate surgical resection of bilateral occipital lobe lesions during a single operation as a treatment for bilateral occipital lobe epilepsy.METHODS This retrospective case series included patients with drug-refractory bilateral occipital lobe epilepsy treated surgically between March 2006 and November 2015.RESULTS Preoperative evaluation included scalp video-electroencephalography(EEG),magnetic resonance imaging,and PET-CT.During surgery(bilateral occipital craniotomy),epileptic foci and important functional areas were identified by EEG(intracranial cortical electrodes)and cortical functional mapping,respectively.Patients were followed up for at least 5 years to evaluate treatment outcome(Engel grade)and visual function.The 20 patients(12 males)were aged 4-30 years(median age,12 years).Time since onset was 3-20 years(median,8 years),and episode frequency was 4-270/mo(median,15/mo).Common manifestations were elementary visual hallucinations(65.0%),flashing lights(30.0%),blurred vision(20.0%)and visual field defects(20.0%).Most patients were free of disabling seizures(Engel grade I)postoperatively(18/20,90.0%)and at 1 year(18/20,90.0%),3 years(17/20,85.0%)and≥5 years(17/20,85.0%).No patients were classified Engel grade IV(no worthwhile improvement).After surgery,there was no change in visual function in 13/20(65.0%),development of a new visual field defect in 3/20(15.0%),and worsening of a preexisting defect in 4/20(20.0%).CONCLUSION Resection of bilateral occipital lobe lesions during a single operation may be applicable in bilateral occipital lobe epilepsy.展开更多
Abdominal epilepsy is often unrecognised as an epilepsy condition, particularly in adults. We present a rare adult patient who suffers daily episodes of abdominal pinching pain described lasting for 30 seconds, often ...Abdominal epilepsy is often unrecognised as an epilepsy condition, particularly in adults. We present a rare adult patient who suffers daily episodes of abdominal pinching pain described lasting for 30 seconds, often evolving to loss of consciousness. Scalp EEG-video monitoring showed interictal left temporal slowing and frequent left temporal epileptiform discharges. Three stereotypical complex partial seizures consistent with her habitual attacks were recorded. Two seizures showed a left temporal onset and whereas the third one appeared to start on the right temporal lobe. In patients with paroxysms of abdominal pain, nausea or vomiting, abdominal epilepsy should be considered after exclusion of the most common aetiologies for gastrointestinal conditions.展开更多
The efficacy and the tolerance of the AEDs have been extensibly studied in the past, however the effects of them on the EEG activity of epileptic patients have been scarcely studied. Eslicarbazepine is a third generat...The efficacy and the tolerance of the AEDs have been extensibly studied in the past, however the effects of them on the EEG activity of epileptic patients have been scarcely studied. Eslicarbazepine is a third generation blocker-sodium channels AED associated with a high reduction in the rate of partial seizures in epileptic patients. We designed an open label, non control study to determine the effects of Eslicarbazepine on the EEG activity of EP with focal seizures in a 12-week follow up. The EP with focal paroxystical activity enrolled in this study showed a statistical significant reduction in the rate of monthly seizures when Eslicarbazepine 800 mgs was added to a previous AED compared to those patients who only received an increase of the AED in monotherapy, concomitantly, EP treated with ESL added to a previous AED showed a statistically significant reduction in the mean occipital frequency and voltage amplitude in the central and parietal regions in the twelfth-week EEG compared to the control group.展开更多
Background and objective: Generating and characterizing primate models of epileptic seizures are important for understanding pathophysiology of diseases and establishing preclinical efficacy of novel therapies like De...Background and objective: Generating and characterizing primate models of epileptic seizures are important for understanding pathophysiology of diseases and establishing preclinical efficacy of novel therapies like Deep Brain Stimulation. A focal motor epilepsy model is described here. Method: Seizures were obtained after intracortical penicillin injection into the motor strip through a cannula in two awake monkeys and electrocorticograms were recorded by epidural screws. Seizures were analyzed and compared for number, average duration of each seizure and total duration of ictal activity. Pharmaco-resistance for antiepileptic drug was tested by administration of Diazepam during seizures. Results: A motor status with seizures mimicking those seen in Kojevnikov’s syndrome was easily generated several minutes after penicillin injection and lasted 24 h on an average. The model thus characterized appears stable and consistent. There is no significant variation between experiments in individual primate as well as between two specimens. Diazepam though reduced the total duration of seizures, failed to abolish behavioural seizures. Conclusion: This model represents a good alternative model for preclinical research aiming at testing novel therapies because seizures are obtained on demand, last up to 24 h after a single penicillin injection, are stable and resistant to Diazepam.展开更多
<strong>Background:</strong> Anterior Corpus Callosotomy is a palliative treatment for drug-resistant generalized or multifocal epilepsy patients where focus excision is not an option for management. Callo...<strong>Background:</strong> Anterior Corpus Callosotomy is a palliative treatment for drug-resistant generalized or multifocal epilepsy patients where focus excision is not an option for management. Callosotomy prevents propagation of epileptic discharge from one cerebral hemisphere to the other. <strong>Objective: </strong>To describe Al-Azhar University Hospitals experience and clinical outcome of Anterior Corpus Callosotomy for management of drug-resistant generalized epilepsy patients as an inexpensive palliative method. <strong>Patients and Methods:</strong> In this study, there are 15 patients admitted to Neurosurgery Department in Al-Azhar University Hospitals with drug-resistant generalized epilepsy. These patients were not candidates for lesionectomy. They were managed by anterior two thirds Corpus Callosotomy between February 2017 and December 2019. They were followed at outpatient clinic for at least 14 months. Clinical outcome regarding seizure control was assessed using Engel classification. <strong>Results:</strong> All 15 patients in this study underwent anterior two thirds corpus callosotomy and followed for at least 14 months. The post-operative improvement of seizure frequency has been evaluated using Engel outcome scale with 12 patients (80%) of the patients becoming Engel class II and 3 patients (20%) becoming Engel class III. Only 3 patients (20%) had minor transient postoperative complications;one patient (6.67%) had contra-lateral lower limb heaviness Grade 4 which was transient, one patient (6.67%) had contra-lateral lower limb Jacksonian focal fits and one patient (6.67%) had behavioral changes for one month. <strong>Conclusion:</strong> Corpus callosotomy is a palliative procedure and inexpensive method for management of patients with intractable focal with generalization and generalized drug-resistant epilepsy who are not suitable for resective surgery and with good outcome.展开更多
目的探讨局灶性癫痫围发作期心率变异性变化特点。方法收集2014年9月至2019年9月在首都医科大学附属北京天坛医院癫痫中心进行术前评估并完成手术的癫痫患者102例,选择局灶性发作198次,手动测量相邻两个心电活动的RR间期,计算心率变异...目的探讨局灶性癫痫围发作期心率变异性变化特点。方法收集2014年9月至2019年9月在首都医科大学附属北京天坛医院癫痫中心进行术前评估并完成手术的癫痫患者102例,选择局灶性发作198次,手动测量相邻两个心电活动的RR间期,计算心率变异性时域参数-相邻正常心跳间期差值平方和的均方根(RMSSD),比较发作前60 s、发作期、终止后60 s RMSSD差异,并比较不同心率变化类型、不同发作类型、不同发作前状态以及不同致痫灶部位和侧别RMSSD差异。结果发作期和发作前60 s及终止后60 s RMSSD相比差异有统计学意义(P<0.001),提示发作期RMSSD降低;心率增快类型癫痫发作期RMSSD降低(P<0.001);复杂部分性癫痫发作期RMSSD降低(P<0.001);颞叶内侧癫痫发作期RMSSD降低(右颞叶内侧P<0.001;左颞叶内侧P<0.001);心率无变化(P=0.556)和心率减慢(P=0.983)类型癫痫发作、单纯部分性癫痫(P=0.869)、颞叶外侧癫痫(右颞叶外侧P=0.204;左颞叶外侧P=0.849)和颞叶外癫痫(右颞外P=0.188;左颞外P=0.068)发作期RMSSD无降低。发作期和发作前60 s RMSSD差值在睡眠期更明显(P=0.039)。结论心率增快类型癫痫发作、复杂部分性癫痫、颞叶内侧癫痫发作期易发生心率变异性下降,提示癫痫发作期副交感活性下降;睡眠期状态下发生的癫痫发作期心率变异性下降相比清醒期显著,提示睡眠期癫痫发作副交感活性下降更加明显。展开更多
Recently,a novel workflow known as the virtual epileptic patient(VEP)has been proposed by a research team from Aix Marseille Universitéin their papers published in Lancet Neurology,Science Translational Medicine ...Recently,a novel workflow known as the virtual epileptic patient(VEP)has been proposed by a research team from Aix Marseille Universitéin their papers published in Lancet Neurology,Science Translational Medicine and Epilepsia.This method involves creating an individualized virtual brain model based on computational modelling,which can facilitate clinical decision-making by estimating the epileptogenic zone and performing the virtual surgery.Here,we summarize brief workflow,strengths,and limitations of VEP,as well as its performance in a retrospective study of 53 patients with drug-resistant focal epilepsy who underwent stereoelectroencephalography.A large-scale clinical trial(NCT03643016)is underway to further assess VEP,which is expected to enroll 356 patients prospectively.As supporting evidence accumulates,the clinical application of VEP has the potential to improve clinical practice,leading to better outcomes and qualities of life of patients.展开更多
基金Supported by Tsinghua University Initiative Scientific Research Program(No.2015THZ01)
文摘For some patients with drug-resistant focal epilepsy, we usually select conventional surgical resection, which has brought better outcomes. However, others are not eligible for a conventional open surgical resection of the epileptogenic zone because of the proximity of a functional area or the implication of a larger epileptogenic network. Initially, stereoelectroencephalography(SEEG) exploration was a method of electroencephalography recording that was used in the presurgical evaluation of epileptic patients with complex epilepsy. Later, intracerebral electrodes used for SEEG were applied to produce radio frequency thermocoagulation(RF-TC) in epileptic patients. SEEG-guided RF-TC has produced some promising results, especially in the last dacade. Now, it has become popular as a palliative treatment to reduce seizure frequency in patients with drug-resistant focal epilepsy. This article presents a review of SEEG-guided RF-TC.
文摘Background:Pentylenetetrazole kindling has long been used for the screening of investigational antiseizure drugs.The presence of lamotrigine,at a very low dose,does not hamper kindling in mice;rather it modifies this epileptogenesis process into drug-resistant epilepsy.The lamotrigine-pentylenetetrazole kindled mice show resistance to lamotrigine,phenytoin,and carbamazepine.It may also be possible that other licensed antiseizure drugs,like the mentioned drugs,remain ineffective in this model;therefore,this was the subject of this study.Methods:Swiss albino mice were kindled with pentylenetetrazole for 35 days in the presence of either methylcellulose vehicle or lamotrigine(subtherapeutic dose,ie,5 mg/kg).Vehicle vs lamotrigine-kindled mice were compared in terms of(a)resistance/response toward nine antiseizure drugs applied as monotherapies and two drug combinations;(b)lamotrigine bioavailability in blood and brain;(c)blood-brain barrier integrity;and(d)amino acids and monoamines in the cerebral cortex and hippocampus.Results:Lamotrigine vs vehicle-kindled mice are similar(or not significantly different P>.05 from each other)in terms of(a)response toward drug combinations;(b)lamotrigine bioavailability;and(c)blood-brain barrier integrity except for,significantly(P<.05)reduced taurine and increased glutamate in the cerebral cortex and hippocampus.Aside from these,lamotrigine-kindled mice show significant(P<.05)resistant to lamotrigine(15 mg/kg),levetiracetam(40 mg/kg);carbamazepine(40 mg/kg),zonisamide(100 mg/kg),gabapentin(224 mg/kg),pregabalin(30 mg/kg),phenytoin(35 mg/kg),and topiramate(300 mg/kg).Conclusion:Lamotrigine-pentylenetetrazole kindling takes longer to develop(~5 weeks)in comparison to lamotrigine-amygdale(~4 weeks)and lamotriginecorneal(~2 weeks)kindling models.However,drug screening through this model may yield superior drugs with novel antiseizure mechanisms.
基金supported by the National Natural Science Foundation of China,Nos. 81760247, 82171450the Scientific Research Foundation for Doctors of the Affiliated Hospital of Zunyi Medical University,No.(2016)14 (all to HH)。
文摘Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.
文摘BACKGROUND Perampanel(PER),a third-generation antiepileptic drug,is a selective and noncompetitiveα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist,and has been approved for the treatment of adults and adolescents with focal epilepsy.However,there are only a few studies about the efficacy and tolerability of PER in young children with multidrug-resistant epilepsy.In this case,we aimed to share our clinical experience in this group.CASE SUMMARY A 4-year-old boy without perinatal asphyxia and familial history of epilepsy began to have ictal seizures from age 14 mo,with jerky movement of four limbs and head nodding.Abnormal multifocal discharge and background activity were recorded through electroencephalography,and no pathogenic mutation was found in the whole exome sequencing for the patient and his parents.He had received valproate,levetiracetam,topiramate,oxcarbazepine,clonazepam and lacosamide sequentially at different times,but he still had frequent seizures even after vagus nerve stimulation(VNS)implantation.He was diagnosed with idiopathic multidrug-resistant epilepsy.However,his seizure frequency was significantly reduced after PER administration in a dose-dependent manner,and better cognitive behavior was observed.In addition,the adverse reactions of anger and aggression also appeared.CONCLUSION PER is effective as add-on therapy for young children with multidrug-resistant epilepsy who have previously undergone VNS implantation.
文摘Background: Drug-resistant epilepsy can be defined as the existence of seizures within 6 months, despite adequate therapy regimens with one or more antiepileptic drugs. Epilepsy surgery has been the standard therapy to help those patients who suffer from drug-resistant epilepsy. The goal of this surgery is to halt or reduce the intensity of seizures. This literature review aims to provide an overview of existing surgical procedures for the treatment of drug-resistant epilepsy and the degree of seizure control they provide based on available literature. Methods: Data were collected from medical journal databases, aggregators, and individual publications. The most used databases were PubMed, Medline and NCBI. Some of the keywords used to search these databases include: “drug resistant epilepsy”, “seizure control”, and “neurosurgery”. Results: Epileptic surgery is divided into resective and non-resective procedures. Studies have shown that a full resection of the epileptogenic brain area increases the probability of seizure eradication, however, the risks of postoperative impairments grow as the resection area is extended. On the other hand, patients who are unsuitable for seizure focus removal by resective surgery, such as those with multifocal seizures or overlapping epileptogenic zone with a functional cortex, may benefit from non-resective surgical options such as Vagus Nerve Stimulation and Responsive Neurostimulation. Conclusion: This literature review discusses the comprehensive treatment of epilepsy, especially the surgical treatment of drug-resistant epilepsy. The reviewed studies have shown that epilepsy surgery has promising outcomes in achieving seizure freedom/reducing seizure frequency with minimal adverse effects when performed correctly with the appropriate choice of surgical candidates.
基金funded by the Key Project of Gansu Province, No.2GS054-A43-014-19
文摘One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 （34% of 86）; the total number of abnormal perfusion foci decreased by 52 （36%） and changes in abnormal loci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.
文摘There have been many advances in the diagnosis and management of focal epilepsies particularly with neuroimaging techniques and magnetic resonance imaging(MRI).Special MRI sequences can be employed to localize and resect the epileptogenic lesions responsible for focal epilepsy.This study aims to show the benefit of dedicated epilepsy MRI sequences in the diagnosis of focal epilepsies.A general electric 1.5 Tesla MRI machine was used with standard and special sequences.Also,a Nihon Kohden electroencephalography(EEG)machine was used.This is a prospective observational study that included 51 patients with focal epilepsies who had an initial negative brain imaging.They underwent epilepsy MRI sequences along with a prolonged video EEG monitoring to localize the lesion,and then results were analyzed statistically using SPSS 22 program.The majority of patients were males(62.75%)with a mean age of 30 years.The grand majority of patients(74.5%,p value of 0.001)had their lesion localized by the epilepsy MRI.The most commonly found pathology was mesial temporal sclerosis.A significant number of patients(23.5%)were sent for an epilepsy surgery(p value 0.002).This study shows the significant impact of dedicated epilepsy MRI sequences on the diagnosis and management of focal epilepsy in the Lebanese population.
基金supported by Guangzhou Science and Technology Planning Project(No.202102080427)China Association against Epilepsy research foundation(No.CJ-2022-018).
文摘Background Medium-chain triglyceride ketogenic diet(MCTKD)is previously less commonly used in China.This study was aimed to assess the efficacy and safety of the modified MCTKD in the treatment of drug-resistant epilepsy in Chinese patients.Methods Patients with drug-resistant epilepsy were enrolled to receive treatment with modified MCTKD in Guangdong Sanjiu Brain Hospital during December 2020 and September 2022.The modified MCTKD contained fat that provided 50–70%of the total energy,as well as proteins and carbohydrates that provided 20–30%and 20%of energy,respectively.The fat component was composed of 20–30%medium-chain triglycerides(MCTs)and 30–40%long-chain triglycerides.The efficacy and safety of the diet were assessed at 1,3 and 6 months.Results A total of 123 patients aged 2.5 to 65 years,were included in this study.The response rates at 1,3 and 6 months were 49.6%,43.1%,and 30.9%,respectively.The seizure freedom rates at 1,3 and 6 months were 12.2%,10.6%,and 6.5%,respectively.The retention rates at 1,3 and 6 months were 98.4%,65.0%and 33.3%respectively.Side effects occurred in 21.14%of patients,which were predominantly gastrointestinal symptoms such as abdominal pain,diarrhea,vomiting,and constipation,and most of them resolved after dietary adjustments.A total of 82 patients(66.7%)discontinued the treatment with the reason of refusing to eat(8.1%),poor efficacy(35.0%),poor compliance(4.9%),and inability to follow-up(9.8%).Only 4 patients(3.3%)withdrew the diet due to side effects.Conclusions The modified MCTKD with MCTs providing 20–30%of energy has a good safety in patients with drug-resistant epilepsy,but its effectiveness needs to be enhanced.Further modifications of MCTKD with an optimal energy ratio are required to achieve a better efficacy and safety.
文摘BACKGROUND Neurosurgical treatment of severe bilateral occipital lobe epilepsy usually involves two operations several mos apart.AIM To evaluate surgical resection of bilateral occipital lobe lesions during a single operation as a treatment for bilateral occipital lobe epilepsy.METHODS This retrospective case series included patients with drug-refractory bilateral occipital lobe epilepsy treated surgically between March 2006 and November 2015.RESULTS Preoperative evaluation included scalp video-electroencephalography(EEG),magnetic resonance imaging,and PET-CT.During surgery(bilateral occipital craniotomy),epileptic foci and important functional areas were identified by EEG(intracranial cortical electrodes)and cortical functional mapping,respectively.Patients were followed up for at least 5 years to evaluate treatment outcome(Engel grade)and visual function.The 20 patients(12 males)were aged 4-30 years(median age,12 years).Time since onset was 3-20 years(median,8 years),and episode frequency was 4-270/mo(median,15/mo).Common manifestations were elementary visual hallucinations(65.0%),flashing lights(30.0%),blurred vision(20.0%)and visual field defects(20.0%).Most patients were free of disabling seizures(Engel grade I)postoperatively(18/20,90.0%)and at 1 year(18/20,90.0%),3 years(17/20,85.0%)and≥5 years(17/20,85.0%).No patients were classified Engel grade IV(no worthwhile improvement).After surgery,there was no change in visual function in 13/20(65.0%),development of a new visual field defect in 3/20(15.0%),and worsening of a preexisting defect in 4/20(20.0%).CONCLUSION Resection of bilateral occipital lobe lesions during a single operation may be applicable in bilateral occipital lobe epilepsy.
文摘Abdominal epilepsy is often unrecognised as an epilepsy condition, particularly in adults. We present a rare adult patient who suffers daily episodes of abdominal pinching pain described lasting for 30 seconds, often evolving to loss of consciousness. Scalp EEG-video monitoring showed interictal left temporal slowing and frequent left temporal epileptiform discharges. Three stereotypical complex partial seizures consistent with her habitual attacks were recorded. Two seizures showed a left temporal onset and whereas the third one appeared to start on the right temporal lobe. In patients with paroxysms of abdominal pain, nausea or vomiting, abdominal epilepsy should be considered after exclusion of the most common aetiologies for gastrointestinal conditions.
文摘The efficacy and the tolerance of the AEDs have been extensibly studied in the past, however the effects of them on the EEG activity of epileptic patients have been scarcely studied. Eslicarbazepine is a third generation blocker-sodium channels AED associated with a high reduction in the rate of partial seizures in epileptic patients. We designed an open label, non control study to determine the effects of Eslicarbazepine on the EEG activity of EP with focal seizures in a 12-week follow up. The EP with focal paroxystical activity enrolled in this study showed a statistical significant reduction in the rate of monthly seizures when Eslicarbazepine 800 mgs was added to a previous AED compared to those patients who only received an increase of the AED in monotherapy, concomitantly, EP treated with ESL added to a previous AED showed a statistically significant reduction in the mean occipital frequency and voltage amplitude in the central and parietal regions in the twelfth-week EEG compared to the control group.
基金supported by“Fondation de l’avenir”and Medtronic Europe.
文摘Background and objective: Generating and characterizing primate models of epileptic seizures are important for understanding pathophysiology of diseases and establishing preclinical efficacy of novel therapies like Deep Brain Stimulation. A focal motor epilepsy model is described here. Method: Seizures were obtained after intracortical penicillin injection into the motor strip through a cannula in two awake monkeys and electrocorticograms were recorded by epidural screws. Seizures were analyzed and compared for number, average duration of each seizure and total duration of ictal activity. Pharmaco-resistance for antiepileptic drug was tested by administration of Diazepam during seizures. Results: A motor status with seizures mimicking those seen in Kojevnikov’s syndrome was easily generated several minutes after penicillin injection and lasted 24 h on an average. The model thus characterized appears stable and consistent. There is no significant variation between experiments in individual primate as well as between two specimens. Diazepam though reduced the total duration of seizures, failed to abolish behavioural seizures. Conclusion: This model represents a good alternative model for preclinical research aiming at testing novel therapies because seizures are obtained on demand, last up to 24 h after a single penicillin injection, are stable and resistant to Diazepam.
文摘<strong>Background:</strong> Anterior Corpus Callosotomy is a palliative treatment for drug-resistant generalized or multifocal epilepsy patients where focus excision is not an option for management. Callosotomy prevents propagation of epileptic discharge from one cerebral hemisphere to the other. <strong>Objective: </strong>To describe Al-Azhar University Hospitals experience and clinical outcome of Anterior Corpus Callosotomy for management of drug-resistant generalized epilepsy patients as an inexpensive palliative method. <strong>Patients and Methods:</strong> In this study, there are 15 patients admitted to Neurosurgery Department in Al-Azhar University Hospitals with drug-resistant generalized epilepsy. These patients were not candidates for lesionectomy. They were managed by anterior two thirds Corpus Callosotomy between February 2017 and December 2019. They were followed at outpatient clinic for at least 14 months. Clinical outcome regarding seizure control was assessed using Engel classification. <strong>Results:</strong> All 15 patients in this study underwent anterior two thirds corpus callosotomy and followed for at least 14 months. The post-operative improvement of seizure frequency has been evaluated using Engel outcome scale with 12 patients (80%) of the patients becoming Engel class II and 3 patients (20%) becoming Engel class III. Only 3 patients (20%) had minor transient postoperative complications;one patient (6.67%) had contra-lateral lower limb heaviness Grade 4 which was transient, one patient (6.67%) had contra-lateral lower limb Jacksonian focal fits and one patient (6.67%) had behavioral changes for one month. <strong>Conclusion:</strong> Corpus callosotomy is a palliative procedure and inexpensive method for management of patients with intractable focal with generalization and generalized drug-resistant epilepsy who are not suitable for resective surgery and with good outcome.
文摘目的探讨局灶性癫痫围发作期心率变异性变化特点。方法收集2014年9月至2019年9月在首都医科大学附属北京天坛医院癫痫中心进行术前评估并完成手术的癫痫患者102例,选择局灶性发作198次,手动测量相邻两个心电活动的RR间期,计算心率变异性时域参数-相邻正常心跳间期差值平方和的均方根(RMSSD),比较发作前60 s、发作期、终止后60 s RMSSD差异,并比较不同心率变化类型、不同发作类型、不同发作前状态以及不同致痫灶部位和侧别RMSSD差异。结果发作期和发作前60 s及终止后60 s RMSSD相比差异有统计学意义(P<0.001),提示发作期RMSSD降低;心率增快类型癫痫发作期RMSSD降低(P<0.001);复杂部分性癫痫发作期RMSSD降低(P<0.001);颞叶内侧癫痫发作期RMSSD降低(右颞叶内侧P<0.001;左颞叶内侧P<0.001);心率无变化(P=0.556)和心率减慢(P=0.983)类型癫痫发作、单纯部分性癫痫(P=0.869)、颞叶外侧癫痫(右颞叶外侧P=0.204;左颞叶外侧P=0.849)和颞叶外癫痫(右颞外P=0.188;左颞外P=0.068)发作期RMSSD无降低。发作期和发作前60 s RMSSD差值在睡眠期更明显(P=0.039)。结论心率增快类型癫痫发作、复杂部分性癫痫、颞叶内侧癫痫发作期易发生心率变异性下降,提示癫痫发作期副交感活性下降;睡眠期状态下发生的癫痫发作期心率变异性下降相比清醒期显著,提示睡眠期癫痫发作副交感活性下降更加明显。
基金This work was supported by the National Key R&D Program of China(No.2022YFC2503800)the National Natural Science Foundation of China(No.82071454)Beijing Municipal Science&Technology Commission(No.Z211100002921032).
文摘Recently,a novel workflow known as the virtual epileptic patient(VEP)has been proposed by a research team from Aix Marseille Universitéin their papers published in Lancet Neurology,Science Translational Medicine and Epilepsia.This method involves creating an individualized virtual brain model based on computational modelling,which can facilitate clinical decision-making by estimating the epileptogenic zone and performing the virtual surgery.Here,we summarize brief workflow,strengths,and limitations of VEP,as well as its performance in a retrospective study of 53 patients with drug-resistant focal epilepsy who underwent stereoelectroencephalography.A large-scale clinical trial(NCT03643016)is underway to further assess VEP,which is expected to enroll 356 patients prospectively.As supporting evidence accumulates,the clinical application of VEP has the potential to improve clinical practice,leading to better outcomes and qualities of life of patients.
