Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

Electroencephalography in the diagnosis and management of treatment-resistant depression with comorbid epilepsy:a novel strategy

INTRODUCTION.Depression,a common mental disorder,is a leading cause of disability worldwide,with a global prevalence ranging from 20% to 25% in women and 7% to 12% in men,and it has exhibited an increasing trend in recent decades.Despite being known for decades,a consensus on the definition and diagnosis of treatment-resistant depression(TRD)is still lacking.

Dedicated Magnetic Resonance Imaging Sequences:Contribution in the Diagnosis of Focal Epilepsy in the Lebanese Population

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.

Significance of ambulatory electroencephalography for differential diagnosis of epilepsy and syncope

BACKGROUND： Twenty-four hour ambulatory electroencephatography （AEEG） provides advantages for continuous electroencephalogram, monitoring brief loss of consciousness complicated by suspect or mild limb spasm. OBJECTIVE： To explore the significance of AEEG for differentially diagnosing epilepsy and syncope, compared to EEG. DESIGN, TIME AND SETTING： Sixty patients with brief loss of consciousness, complicated by suspect or mild limb spasm, were selected from Suqian People＇s Hospital between January 2006 and June 2007. PARTICIPANTS： Sixty participants comprised 34 males and 26 females, aged 13-64 years. According to clinical symptoms prior to the study, 36 patients were initially diagnosed with epilepsy and 24 with syncope. METHODS AND MAIN OUTCOME MEASURES： Abnormalities and epileptiform discharge were detected using EEG and AEEG, and the diagnostic value of the two methods for epilepsy and syncope was compared. RESULTS： A total of sixty patients were included in the final analysis. Abnormal AEEGs were observed in 37 cases （62%） and epileptiform discharge AEEGs in 23 cases （38%）, both of which were significantly greater than EEGs [37% （22/60）, 18% （11/60）, respectively, P 〈 0.01, 0.05]. The detection rate of abnormal AEEG and epileptiform discharge in the epilepsy group [75% （27/36）, 47% （17/36）, respectively was significantly greater than in the syncope group [42% （10/24）, 25% （6/24）, respectively, P 〈 0.01, 0.05]. CONCLUSION： AEEG can improve detection probability of epileptiform discharge and exhibits significant differences in the differential diagnosis of epilepsy and syncope.

Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

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.

Frequency of Juvenile Myoclonic Epilepsy Clinical Phenotypes in Siberia

Juvenile myoclonic epilepsy (JME) is characterised by myoclonia during awakening, generalised tonic-clonic seizures, typical absences and usually presents for the first time at the age of 12 to 18 years old. This article describes the results of a clinical study into JME phenotypes in patients living in the Siberian Federal District. We have shown that the incidence of JME among males was lower than among females (1:1.9) and JME debut age for males was higher than in those women. Classical phenotype of JME (Type I) was dominant and more common in males compared to females—70.4% vs. 58.5%, respectively. The JME phenotype with worse prognosis in terms of achieving stable clinical remission (Type II) occurred 3.5 times more frequently among female patients compared to male (13.2% vs. 3.7% respectively). The findings resulting from this study give a deeper insight into the diagnosis and prognosis of this form of idiopathic generalised epilepsy in predisposed families.

Case Report of Management Problem of Juvenile Myoclonic Epilepsy

Juvenile myoclonic epilepsy (JME) is one of the most common types of idiopathic generalised epilepsy. It starts in teenage years, yet it is frequently misdiagnosed or diagnosed very late, thereby resulting in inadequate therapy plan and worsening of symptoms. Timely diagnosis of JME is crucial for the correct management of symptoms and prevention of disease development. In this case report we describe a case of a 33-year-old woman who did not receive appropriate care due to a late diagnosis of her JME condition.

Temporal Epilepsy Causing Recurrent Abdominal Pain in Adults

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.

Functional characterization of novel NPRL3 mutations identified in three families with focal epilepsy

Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study,three novel mutations in NPRL3(nitrogen permease regulator-like 3), c.937_945del, c.1514dup C and 6,706-bp genomic DNA(g DNA) deletion, were identified in three families with focal epilepsy by linkage analysis, whole exome sequencing(WES) and Sanger sequencing. NPRL3 protein is a component of the GATOR1 complex, a major inhibitor of m TOR signaling. These mutations led to truncation of the NPRL3 protein and hampered the binding between NPRL3 and DEPDC5, which is another component of the GATOR1 complex. Consequently, the mutant proteins enhanced m TOR signaling in cultured cells, possibly due to impaired inhibition of m TORC1 by GATOR1. Knockdown of nprl3 in Drosophila resulted in epilepsy-like behavior and abnormal synaptic development. Taken together, these findings expand the genotypic spectrum of NPRL3-associated focal epilepsy and provide further insight into how NPRL3 mutations lead to epilepsy.

Psychogenic non‑epileptic seizures (PNES)in the context of concurrent epilepsy-making the right diagnosis

Epilepsy is a risk factor for the development of psychogenic non-epileptic seizures(PNES)and comorbid epilepsy is recognized as a comorbidity in about 10–30%of patients with PNES.The combination of epileptic and nonepileptic seizures poses a particular diagnostic challenge.In patients with epilepsy,additional PNES may be suspected on the basis of their typical semiology.The possibility of additional PNES should also be considered if seizures fail to respond to antiepileptic drug treatment,in patients with frequent emergency admissions with seizures and in those who develop new types of seizures.The description of semiological details by patients and witnesses can suggest additional PNES.Home video recordings can support an initial diagnosis,however,especially in patients with mixed seizure disorders it is advisable to seek further diagnostic confirmation by capturing all habitual seizure types with video-EEG.The clinical features of PNES associated with epilepsy are similar to those in isolated PNES disorders and include longer duration,fluctuating course,asynchronous movements,pelvic thrusting,side-to-side head or body movement,persistently closed eyes and mouth,ictal crying,recall of ictal experiences and absence of postictal confusion.PNES can also present as syncope-like episodes with unresponsiveness and reduced muscle tone.There is no unique epileptological or brain pathology profile putting patients with epilepsy at risk of additional PNES.However,patients with epilepsy and PNES typically have lower educational achievements and higher levels of psychiatric comorbidities than patients with epilepsy alone.Psychological trauma,including sexual abuse,appears to be a less relevant aetiological factor in patients with mixed seizure disorders than those with isolated PNES,and the gender imbalance(i.e.the greater prevalence in women)is less marked in patients with PNES and additional epilepsy than those with PNES alone.PNES sometimes develop after epilepsy surgery.A diagnosis of‘known epilepsy’should never be accepted without(at least brief)critical review.This narrative review summarises clinical,electrophysiological and historical features that can help identify patients with epilepsy and additional PNES.

MicroRNAs as biomarkers in molecular diagnosis of refractory epilepsy

MicroRNA (miRNA) is a type of endogenous non-coding RNA that can regulate cell proliferation,differentiation,invasion,apoptosis and several other biological activities by specially inducing gene silencing,and thereby is related to development and disease in life course.In recent years,researchers have found that miRNAs are closely related with refractory epilepsy.MiRNAs can intervene in the modification of mRNAs,the synthesis of proteins and some the connectivity of signal pathways in pathogenesis of epilepsy.Furthermore,some miRNAs in neurons are of great importance in neuronal differentiation.Therefore,miRNA may play a very important role in the occurrence,development and episodes of refractory epilepsy.These discoveries can provide a new direction for the research of pathogenesis,diagnostic methods and therapeutic approach of refractory epilepsy.Although research about miRNA and intractable epilepsy has progressed,more remains to be done before miRNA can be used in clinical diagnosis and treatment strategies.This paper focuses on the research progress of molecular diagnosis about miRNA in intractable epilepsy.

Differential diagnosis of different types of solid focal liver lesions using two-dimensional shear wave elastography

BACKGROUND The clinical management and prognosis differ between benign and malignant solid focal liver lesions(FLLs),as well as among different pathological types of malignant FLLs.Accurate diagnosis of the possible types of solid FLLs is important.Our previous study confirmed the value of shear wave elastography(SWE)using maximal elasticity(Emax)as the parameter in the differential diagnosis between benign and malignant FLLs.However,the value of SWE in the differential diagnosis among different pathological types of malignant FLLs has not been proved.AIM To explore the value of two-dimensional SWE(2D-SWE)using Emax in the differential diagnosis of FLLs,especially among different pathological types of malignant FLLs.METHODS All the patients enrolled in this study were diagnosed as benign,malignant or undetermined FLLs by conventional ultrasound.Emax of FLLs and the periphery of FLLs was measured using 2D-SWE and compared between benign and malignant FLLs or among different pathological types of malignant FLLs.RESULTS The study included 32 benign FLLs in 31 patients and 100 malignant FLLs in 96 patients,including 16 cholangiocellular carcinomas(CCCs),72 hepatocellular carcinomas(HCCs)and 12 liver metastases.Thirty-five FLLs were diagnosed as undetermined by conventional ultrasound.There were significant differences between Emax of malignant(2.21±0.57 m/s)and benign(1.59±0.37 m/s)FLLs(P=0.000),and between Emax of the periphery of malignant(1.52±0.39 m/s)and benign(1.36±0.44 m/s)FLLs(P=0.040).Emax of liver metastases(2.73±0.99 m/s)was significantly higher than that of CCCs(2.14±0.34 m/s)and HCCs(2.14±0.46 m/s)(P=0.002).The sensitivity,specificity and accuracy were 71.00%,84.38%and 74.24%respectively,using Emax>1.905 m/s(AUC 0.843)to diagnose as malignant and 23 of 35(65.74%)FLLs with undetermined diagnosis by conventional ultrasound were diagnosed correctly.CONCLUSION Malignant FLLs were stiffer than benign ones and liver metastases were stiffer than primary liver carcinomas.2D-SWE with Emax was a useful complement to conventional ultrasound for the differential diagnosis of FLLs.

Stereoelectroencephalography-guided radiofrequency thermocoagulation(SEEG-guided RF-TC) in patients with drug-resistant focal epilepsy

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.

Absence seizures in lesion‑related epilepsy

Background In the new International League Against Epilepsy(ILAE)classification of seizure types,generalized seizures such as absence seizures(ASs)may originate from a focal point and rapidly spread to the bilaterally distributed brain network.Increasing evidence from animal and clinical studies has indicated that focal changes may occur prior to ASs;however,the relationship of ASs with epileptogenic lesions remains unclear.Methods We retrospectively collected and analyzed the clinical,imaging,and electrophysiological data of 16 patients who had ASs and structural lesions with seizure-free outcomes after lesion resection.Results In semiology analysis,nine patients displayed focal onset;only two patients showed simple ASs,and seizure types other than ASs were observed in the remaining patients.On ictal electroencephalography(EEG),four patients showed bilateral synchronous symmetric 3 Hz generalized spike-wave discharges(GSWDs),and the remaining patients showed bilateral 1.5–2.5 Hz GSWDs.Moreover,most patients(13/16,81.3%)exhibited focal features in addition to ASs,while interictal EEG was the same in 12 patients.Furthermore,on stereoelectroencephalogram(SEEG),2/5 patients showed focal discharges before bilateral burst GSWDs.Additionally,all patients had structural lesions on imaging.In four typical AS patients,the lesions were located in deep brain regions.Notably,in 9 patients(9/16,56%),the lesions were located in the posterior cortex.All patients underwent lesion resection and had seizure-free outcomes during follow-up,and intelligence quotient(IQ)also improved by 10.71±3.90 one year after surgery.Conclusions Patients with lesion-related epilepsy may present with ASs that have a focal onset and are associated with good surgical outcomes.

Emerging personalized virtual brain models: next-generation resection neurosurgery for drug-resistant epilepsy?

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.

Computer-aided diagnosis for contrast-enhanced ultrasound in the liver

Computer-aided diagnosis(CAD) has become one of the major research subjects in medical imaging and diagnostic radiology.The basic concept of CAD is to provide computer output as a second opinion to assist radiologists' image interpretations by improving the accuracy and consistency of radiologic diagnosis and also by reducing the image-reading time.To date,research on CAD in ultrasound(US)-based diagnosis has been carried out mostly for breast lesions and has been limited in the fields of gastroenterology and hepatology,with most studies being conducted using B-mode US images.Two CAD schemes with contrast-enhanced US(CEUS) that are used in classifying focal liver lesions(FLLs) as liver metastasis,hemangioma,or three histologically differentiated types of hepatocellular carcinoma(HCC) are introduced in this article:one is based on physicians' subjective pattern classifications(subjective analysis) and the other is a computerized scheme for classification of FLLs(quantitative analysis).Classification accuracies for FLLs for each CAD scheme were 84.8% and 88.5% for metastasis,93.3% and 93.8% for hemangioma,and 98.6% and 86.9% for all HCCs,respectively.In addition,the classification accuracies for histologic differentiation of HCCs were 65.2% and 79.2% for well-differentiated HCCs,41.7% and 50.0% for moderately differentiated HCCs,and 80.0% and 77.8% for poorly differentiated HCCs,respectively.There are a number of issues concerning the clinical application of CAD for CEUS,however,it is likely that CAD for CEUS of the liver will make great progress in the future.

脑肿瘤与癫痫的临床及影像相关性探究

目的分析脑肿瘤的临床及影像特征,探讨脑肿瘤与其继发癫痫的相关性。方法选取笔者所在医院34例脑肿瘤且合并癫痫患者作为观察组,随机选取同时期脑肿瘤不伴癫痫症状患者34例作为对照组,统计两组间年龄、性别、肿瘤组织类型、肿瘤部位及影像特征差异,分析两者之间的相关性。结果两组间年龄、性别以及肿瘤组织类型差异没有明显统计学意义,两组间肿瘤分布情况在额叶组中存在统计学差异(P=0.078),两组肿瘤影像学特征在伴局部脑萎缩组中存在统计学差异(P=0.032)。结论脑肿瘤与癫痫发生存在一定相关性,充分运用影像学检查指导这类患者的诊疗能有效地减少癫痫带来的继发损害和潜在危害。

Artificial intelligence analysis of videos to augment clinical assessment:an overview

Observation is a fundamental part of the practice of clinical medicine.Observation of movement is particularly important for the neurologist.Conditions such as Parkinson’s disease,multiple sclerosis,stroke,epilepsy,and many others affect a person’s movement in characteristic ways.In some conditions,changes in the patient’s voice can be included in this-changes in sound caused by changes in the movements of speech.The clinician’s detection of a characteristic abnormality,and their judgment of its severity,plays a central role in both diagnosis and the assessment of prognosis or response to treatment.However,that practice depends upon a limited resource of experienced experts.In addition,these experts are limited by human visual judgment,which cannot reliably or precisely detect and measure small or subtle changes in movement(Williams et al.,2023).

视频脑电图与常规脑电图诊断癫痫的早期效能比较

目的比较视频脑电图(VEEG)与常规脑电图(REEG)诊断癫痫的早期效能。方法回顾性分析2019年5月至2023年5月长春市中心医院收治的104例拟诊癫痫患者的临床资料,所有患者均进行VEEG与REEG监测,比较VEEG与REEG监测效果、检出情况及分型、定位诊断。以病史、临床表现及其他辅助检查结果为金标准,比较VEEG与REEG诊断癫痫的早期效能。结果VEEG监测到的痫样放电率、临床发作率均高于REEG,差异有统计学意义(P<0.05)。VEEG癫痫、非癫痫发作检出率均高于REEG,暂不诊断癫痫检出率低于REEG,差异有统计学意义(P<0.05)。41例癫痫患者中,强直阵挛性发作8例,肌阵挛发作7例,复杂部分性发作8例,全面性发作5例,单纯部分性发作6例,失神发作7例;睡眠期出现异常放电24例,清醒期出现异常放电7例,睡眠期和清醒期均出现异常放电10例;明确痫样放电部位32例,包括颞区发作8例,额区发作7例,额颞区发作6例,中央区发作4例,枕区发作4例,颞枕后区发作3例。根据病史、临床表现以及其他辅助检查结果诊断,104例拟诊癫痫患者中,确诊癫痫患者58例,非癫痫患者46例,VEEG早期诊断癫痫的准确度、灵敏度、特异度、阳性预测值、阴性预测值均高于REEG,差异有统计学意义(P<0.05)。结论VEEG可提高痫样放电和临床发作检出率,还能用于癫痫分型和痫灶定位,在癫痫早期诊断中具有较高准确度,值得临床应用推广。

局灶性癫痫围发作期心率变异性变化特点

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。