MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.

A meta-analysis of risk factors for epilepsy after acute ischaemic stroke and the development of a predictive model

Objective:To screen risk factors for epilepsy after acute ischaemic stroke based on meta-analysis and cohort study and to establish a predictive model.Methods:Computer searches of MEDLINE,Embase,Cochrane library,Web of Scinence,PubMed,CNKI,and WanFang Data data were conducted to collect literature on epilepsy after in acute ischemic stroke,from database creation to September 1,2022.The RRs and their 95%confidence intervals(CI)for risk factors for post stroke epilepsy were extracted for each study,and pooled estimates of the RRs and 95%CIs for each study were generated using either a random-effects model or a fixed-effects model.Beta coefficients for each risk factor were calculated based on the combined RR and their corresponding 95%CIs.The beta coefficients were multiplied by 10 and rounded.Results:Ten articles were identified for final inclusion in this meta-analysis,with a total of 141948 cases and 3702 cases of post stroke epilepsy.The risk factors included in the final risk prediction model were infarct size(RR 4.67,95%CI 1.41~15.47;P=0.01),stroke recuRRence(RR 2.48,95%CI 2.01~3.05;P<0.00001),stroke etiology(RR 1.70,95%CI 1.34~2.15;P<0.00001),stroke severity(RR 1.70,95%CI 1.34~2.15;P<0.00001),and stroke risk.stroke severity(RR 1.53,95%CI 1.39~1.70;P<0.00001),NIHSS score(RR 2.91,95%CI 1.64~5.61;P=0.0003),early-onset epilepsy(RR 5.62,95%CI 5.08~6.22;P<0.00001),cortical lesions(RR 3.83.95%CI 2.23~6.58;P<0.00001),total anterior circulation infarction(RR 18.94,95%CI 10.38~34.57;P<0.00001),partial anterior circulation infarction(RR 4.39,95%CI 2.29~8.40;P<0.00001),cardiovascular events(RR 1.78,95%CI 1.59~1.99;P<0.00001).Conclusion:Based on a systematic review and meta-analysis,we developed a simple risk prediction model for late epilepsy in baseline ischemic stroke that integrates clinical risk factors,including infarct size,stroke recurrence,stroke etiology,stroke severity,NIHSS score,early onset epilepsy,cortical lesions,stroke subtype,and cardiovascular events.

Pharmacokinetic, pharmacodynamic, and neurochemical investigations of lamotrigine-pentylenetetrazole kindled mice to ascertain it as a reliable model for clinical drug-resistant epilepsy

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.

Effect of glutathione on brain nitric oxide levels in an experimental epilepsy mouse model

BACKGROUND： Oxidative stress plays an important role in the pathophysiology of epilepsy. Glutathione, known as one of the compounds of antioxidant defense, has been shown to inhibit convulsions. Nitric oxide has a proconvulsant effect on a pentylenetetrazole-induced animal model. OBJECTIVE： To evaluate the effects of glutathione administration on nitric oxide levels in brain regions of convulsive and kindling pentylenetetrazole-induced seizure models. DESIGN, TIME, AND SETTING： A randomized, controlled, animal experiment. The study was performed at the Department of Physiology, Gaziantep University and Department of Chemistry-Biochemistry,Kahramamaras Sutcu Imam University in 2006. MATERIALS： Pentylenetetrazole and glutathione were purchased from Sigma, USA. METHODS： A total of 80 mice were assigned to 8 groups （n = 10）： normal control, saline control （1 mL normal saline）, convulsive pentylenetetrazole （single intraperitoneal administration of pentylenetetrazole, 60 mg/kg）, convulsive pentylenetrazole plus glutathione （single administration of 60 mg/kg pentylenetetrazole and 200 mg/kg glutathione）, five-dose glutathione （intraperitoneal injection of 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days）, single-dose glutathione （single administration of 200 mg/kg glutathione）, pentylenetetrazole kindling （intraperitoneal administration of pentylenetetrazole of 40 mg/kg at 1,3, 5, 7, and 10 days）, and pentylenetetrazole kindling plus glutathione group （intraperitoneal injection of 40 mg/kg pentylenetetrazole and 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days）. MAIN OUTCOME MEASURES： All mice were sacrificed 1 hour after the last administration. Brain nitric oxide levels were determined by spectrophotometry. RESULTS： There were no significant differences in nitric oxide levels between the normal control, saline control, five-dose glutathione, and single-dose glutathione groups （P 〉 0.05）. Nitric oxide levels in the cerebral hemisphere and cerebellum were significantly less in the convulsive pentylenetetrazole group, compared with the convulsive pentylenetetrazole plus glutathione group （P 〈 0.01）, and levels in the pentylenetetrazole kindling group were remarkably greater than the remaining groups （P 〈 0.01 ）. Brain nitric oxide levels in all groups gradually decreased from the right brain stem to the left brain stem, cerebellum, left cerebral hemisphere, and right cerebral hemisphere. CONCLUSION： Glutathione regulated nitric oxide levels in various brain regions of pentylenetetrazole-induced kindling models, and did not affect nitric oxide levels in the control mice. These results indicated that glutathione played a role when nitric oxide was over-produced. In addition, the brain stem exhibited the highest levels of nitric oxide in both control mice and pentylenetetrazole-induced kindling models.

Comparison between Different ESI Methods on Refractory Epilepsy Patients Shows a High Sensitivity for Bayesian Model Averaging

Electrical Source Imaging (ESI) is a non-invasive technique of reconstructing brain activities using EEG data. This technique has been applied to evaluate epilepsy patients being evaluated for epilepsy surgery, showing encouraging results for mapping interictal epileptiform discharges (IED). However, ESI is underused in planning epilepsy surgery. This is basically due to the wide availability of methods for solving the electromagnetism inverse problem (e-IP) associated to few studies using EEG setups similar to those most commonly used in clinical setting. In this study, we applied six different methods of solving the e-IP based on IEDs of 20 focal epilepsy patients that presented abnormalities in their MRI. We compared the ESI maps obtained by each method with the location of the abnormality, calculating the Euclidian distances from the center of the lesion to the closest border of the method solution (CL-BM) and also to the solution’s maxima (CL-MM). We also applied a score system in order to allow us to evaluate the sensitivity of each method for temporal and extra temporal patients. In our patients, the Bayesian Model Averaging method had a sensitivity of 86% and the shortest CL-MM. This method also had more restricted solutions that were more representative of epileptogenic activities than those obtained by the other methods.

Pial iontophoresis of ferric chloride versus cortical ferric chloride injection in establishing iron-induced posttraumatic epilepsy animal models

BACKGROUND： In order to study the pathogenesis of iron-induced posttraumatic epilepsy （PTE）, foreign scholars have established several kinds of PTE animal models, among which, the iron- induced PTE animal models proposed by Willmore is the most famous. The iron-induced PTE animal models can be established by two methods： one is cortical ferric chloride injection （CFCI） and the other one is pial iontophoresis of ferric chloride （PIFC）. Because Willmore did not give out the elaboration of the behaviors and electroencephalograms （EEGs） of the iron induced PTE animal models established by these two methods, so we have known little about these animal models. OBJECTIVE： To observe the behaviors and EEGs of the iron-induced PTE animal models established by PIFC and CFCI, in order to compare the differences and the study value of these two methods. DESIGN： Qualitative controlled observation tria SETTING： Department of Neurosurgery, Urumqi General Hospital, Lanzhou Military Area Command of Chinese PLA. MATERIALS： Forty healthy adult male SD rats, weighing 200 to 250 g, were involved in this experiment. Reagents and instruments： Ferric chloride （FeCl3·6H2O, Sigma USA）, rat stereotaxic apparatus （ASI company, USA）, the wireless blue tooth electroencephlograms recording system （Nuocheng electric Co.Ltd, Shanghai）, a set of air turbine dental drill unit, dental base acrylic resin powder, microinjector （50 μL）, amperemeter （1 mA）, a pair of batteries, electric resistance （200 kΩ） , variable resistance （100 kΩ）, tubule with endo-meridians of 2 mm （used as import tube）, several silver wire segments and several acupuncture needles were employed in this study. METHODS： This study was carried out in the Experimental Animal Center of the Urumqi General Hospital, Lanzhou Military Area Command of Chinese PLA between November 2004 and April 2005. Establishing the PET animal models by CFCI method： Twenty SD rats were taken, intraperitoneally anesthetized with 50 mg/kg barbanylum and fixed on stereotaxic apparatus. A cranial burr hole with the diameter of 2 mm was drilled 3 mm behind the coronal suture and 2 mm lateral to the sagittal line on the left cranium. Another 5 cranial burr holes with diameter of 2 mm were drilled to place electrodes. The positions of holes were set that taking bregma as original point, sagittal line as Y-axis, the line through the original point and vertical to the Y-axis as X-axis. The unit of the coordinate axis was mm. The coordinate value of the electrodes were （4, 0）, （4, -6）, （-4, 0）, （-4, -6）, at last, a hole with the diameter of 2 mm was drilled on the center of the coronale. 5 μL ferric chloride solution （FeCl3, 100 mmol/L, pH 1.5） was injected into the sensorimotor cortex of rats using microinjector within 5 minutes. The needling depth was 3 mm. The needle was retained for 5 minutes so as to prevent the outflow of liquid. Establishing the PTE animal models by PIFC method： Twenty SD rats were chosen and weighed, and the procedures after weighing were as above.A cranial burr hole with the diameter of 4 mm was drilled in the position where needle inserted in animal models established by CFCI method. Cerebral dura mater was cut. Another 5 holes were drilled to place electrodes in the same position as above. The tip of tubule cotton stuffed inside （to prevent the rapid flow of FeCl3 solution, 100 mmol/L, pH 1.5） was gently connected to cerebral pia mater. The positive and negative electrodes of the amperemeter whose output current was 100 μA were connected to acupuncture needles. The acupuncture needle, which was connected to positive electrode, was inserted into ferric chloride solution, and that which was connected to negative electrode was inserted into the right forelimb of rats subcutaneously. The rats were galvanized for 10 minutes. Record of EEG： The silver wire with blunt anterior extremity was placed on the cerebral dura mater. Then, silver wire and cranial bones were firmly fixed with dental base acrylic resin power. The other side was connected to the wireless blue tooth electroencephlograms recording system to monitor EEG changes. Assessment criteria of seizure degree： Grade Ⅰ ： ＂wet dog-like＂ shudder, facial muscle convulsion and chewing;Grade Ⅱ： rhythmical nodding：Grade Ⅲ： forelimb clonus：Grade Ⅳ： forelimb clonus while standing： Grade Ⅴ： lost the balance, vert, limb＇s convulsion and the whole body＇s tic. MAIN OUTCOME MEASURES： Behaviors and EEGs changes of iron-induced PTE animal models established by PTFC and CFCI. RESULTS： All the 40 rats were involved in the result analysis. （1） The changes of the behaviors： The two animal models both had the epileptic seizures. The epileptic seizure of the animal model established by PIFC mainly presented automatic behavior of chewing, and facial muscle convulsion accompanied with chewing. Epileptic seizure reached the peak within 2.5 to 7 hours after model establishing.It was gradually decreased within 24 hours and hardly seen 1 day after model establishing. The epileptic seizure of the rat model established by CFCI mainly presented turnover upspring and limbs＇ convulsion and urinary incontinence accompanied. The epileptic seizure reached the peak within 3 to 8 hours.It was relatively frequent within 1 week and gradually decreased within 2 weeks after model establishing. The PTE animal models established by CFCI were more closed to clinical PTE process. （2） The form of seizures： The epileptic seizures of the rat model established by PIFC mainly presented grade Ⅰ , seldom presented grades Ⅲ, Ⅳ and Ⅴ; The epileptic seizures of rat model established by CFCI mainly presented the head turning to the right, body＇s rotation, then appeared as grades Ⅳ and Ⅴ, and the whole procedure lasted 1 minute. At the interval of big seizures, grade Ⅰ was observed. From the respect of seizure manifestation, the PTE models established by CFCI were more similar to human PTE. （3） EEGs changes： The sharp waves with average frequency of 9.66 Hz and average amplitude of 183.90 μV were observed on the EEGs of the model established by PIFC when the rats were suffering seizures. The spike waves with average frequency of 16.01 Hz and average amplitude of 143.60 μV were observed on the EEGs of the model established by CFCI when the rats were suffering seizures. CONCLUSTON： （1）Iron-induced PTE rat model is stable and credible. （2）Compared with PTE animal model established by PIFC, PTE animal model established by CFCI is a chronic animal model, and its seizure manifestation is more similar to human PTE. so it is worth further studies.

Features of animal models of complex partial epilepsy established through unilateral,bilateral and alternate-side kindling at hippocampus of rats

BACKGROUND： Electrical stimulation kindling model, having epilepsy-inducing and spontaneous seizure and other advantages, is a very ideal experimental animal model. But the kindling effect might be different at different sites. OBJECTIVE： To compare the features of animal models of complex partial epilepsy established through unilateral, bilateral and alternate-side kindling at hippocampus and successful rate of modeling among these 3 different ways. DESIGN： A randomized and controlled animal experiment SETTING： Department of Neurology, Qilu Hospital, Shandong University MATERIALS： Totally 60 healthy adult Wistar rats, weighing 200 to 300 g, of either gender, were used in this experiment. BL-410 biological functional experimental system （Taimeng Science and Technology Co. Ltd, Chengdu） and SE-7102 type electronic stimulator （Guangdian Company, Japan） were used in the experiment. METHODS： This experiment was carried out in the Experimental Animal Center of Shandong University from April to June 2004. After rats were anesthetized, electrode was implanted into the hippocampus. From the first day of measurement of afterdischarge threshold value, rats were given two-square-wave suprathreshold stimulation once per day with 400 μA intensity, 1ms wave length, 60 Hz frequency for 1 s duration. Left hippocampus was stimulated in unilateral kindling group, bilateral hippocampi were stimulated in bilateral kindling group, and left and right hippocampi were stimulated alternately every day in the alternate-side kindling group. Seizure intensity was scored： grade 0： normal, 1： wet dog-like shivering, facial spasm, such as, winking, touching the beard, rhythmic chewing and so on; 2： rhythmic nodding; 3： forelimb spasm;4： standing accompanied by bilateral forelimb spasm;5： tumbling, losing balance, four limbs spasm. Modeling was successful when seizure intensity reached grade 5. t test was used for the comparison of mean value between two samples. MAIN OUTCOME MEASURES： Comparison of the successful rate of modeling, the times of stimulation to reach intensity of grade 5, the lasting time of seizure of grade 3 of rats in each group. RESULTS： Four rats of alternate-side kindling group dropped out due to infection-induced electrode loss, and 56 rats were involved in the result analysis. The successful rate of unilateral kindling group, bilateral kin- dling group and alternate-side kindling group was 55%（11/20）,100%（16/16）and 100%（20/20）, respective- ly. The stimuli to reach the grade 5 spasm were significantly more in the bilateral kindling group than in the unilateral kindling group [（30.63±3.48）, （19.36±3.47）times, t=8.268, P 〈 0.01], and those were significantly fewer in the alternate-side kindling group than in the unilateral kindling group [（ 10.85±1.98）times, t=-8.744, P 〈 0.01]. The duration of grade 3 spasm was significantly longer in the bilateral kindling group than in the unilateral kindling group [（9.75±2.59）, （3.21 ±1.58）days,t=-8.183,P 〈 0.01], Among 20 successful rats of al- ternate-side kindling group, grade 5 spasm was found in the left hippocampi of 11 rats, but grade 3 spasm in their right hippocampi; Grade 5 spasm was found in the right hippocampi of the other 9 rats, grade 4 spasm in the left hippocampus of 1 rat and grade 3 of 8 rats. CONCLUSION ： The speed of establishing epilepsy seizure model by alternate-side kindling is faster than that by unilateral kindling, while that by bilateral kindling is slower than that by unilateral kindling. The successful rate is very high to establish complex partial epilepsy with alternate-side or bilateral kindling. Epilepsy seizure established by alternate-side kindling has antagonistic effect of kindling and the seizure duration of grade 3 spasm is prolonged.

脑梗死后继发癫痫的危险因素分析及预测模型建立

目的 分析84例脑梗死后继发癫痫的危险因素,并建立XGBoost模型,分析该模型对继发癫痫的预测价值。方法 选取2019年6月至2022年8月郑州大学第一附属医院收治的84例脑梗死后继发癫痫患者纳入研究组,同时选取同期84例脑梗死后未继发癫痫患者纳入对照组。统计研究组癫痫发作情况。通过单因素、多因素logistic回归分析脑梗死后继发癫痫的影响因素。建立XGBoost模型,并采用受试者工作特征曲线、校准曲线分别评价该模型对继发癫痫的预测效果。结果 研究组中早发性癫痫51例、迟发性癫痫33例,单次发作56例、反复发作28例;较大梗死面积、颈动脉循环系统、美国国立卫生研究院卒中量表(NIHSS)评分增加、机械取栓、出血转化及血清同型半胱氨酸(Hcy)、神经元特异性烯醇化酶(NSE)、血清可溶性白细胞介素-2受体(sIL-2R)、脂蛋白相关磷脂酶A2(Lp-PLA2)水平升高是继发癫痫的危险因素(P<0.05);XGBoost模型依据不同危险因素进行重要度评分排序,依次分别为梗死面积、Lp-PLA2水平、NIHSS评分、sIL-2R水平、出血转化、NSE水平、机械取栓、Hcy水平、受累动脉系统;XGBoost模型预测脑梗死后继发癫痫的曲线下面积为0.826,且Hosmer-Lemeshow拟合优度检验(χ^(2)=7.015,P=0.541)。结论 梗死面积增大、颈动脉循环系统、NIHSS评分增加、机械取栓、出血转化及血清Hcy、NSE、sIL-2R、Lp-PLA2水平升高是脑梗死后继发癫痫的危险因素,建立XGBoost模型有助于筛选高危人群,该模型对继发癫痫具有一定预测价值,有助于指导临床防治脑梗死后继发癫痫。

颅骨成形术后癫痫发作的危险因素分析及其预测模型构建

目的探讨可能导致颅骨成形术后癫痫发作(PCS)的危险因素,并构建预测模型。方法回顾性分析163例行颅骨成形术患者的临床资料,根据患者术后有无癫痫发作分为癫痫发作组(35例)和无癫痫发作组(128例)。采用单因素和进一步的多因素Logistic回归分析,探讨可能导致PCS的危险因素,并构建预测模型,利用Hosmer-Lemeshow(H-L)检验及受试者工作特征(ROC)曲线评价该模型对PCS的诊断效能和预测价值。结果共163例患者被纳入本研究,出现PCS的患者共35例,发生率为21.5%。单因素分析显示:两组患者格拉斯哥预后量表(GOS)评分、原发疾病后发生癫痫发作、皮瓣情况比较存在差异(P<0.05)。进一步的多因素Logistic回归分析显示:原发疾病后发生癫痫发作、低GOS评分、皮瓣塌陷>0.5 cm是导致PCS的独立危险因素(P<0.05)。模型logit(P)=5.105+3.266x_(1)-1.775x_(2)-1.241x_(3)-1.576x_(4),经H-L检测显示χ^(2)=6.637(P>0.05),表明模型与观测值具有较好的拟合度;按照诊断几率logit(P)绘制患者PCS的ROC曲线,当logit(P)>5.515时,曲线下面积(AUC)为0.850,95%CI为(0.776,0.925),敏感度为71.4%,特异度为87.5%。结论原发疾病后发生癫痫发作、低GOS评分、皮瓣塌陷>0.5 cm可能增加患者PCS的发生率,构建的预测模型具有较好的区分度、一致性及临床适应性。

基于IMB模型的护理延伸服务对酒精性癫痫患者癫痫发作率及服药依从性的影响

目的探究基于信息-动机-行为技巧(IMB)模型的护理延伸服务对酒精性癫痫患者癫痫发作率及服药依从性的影响。方法选取2020年1月至2022年1月于我院就诊的80例酒精性癫痫男性患者为研究对象,采用随机数字表法将其分为对照组与研究组,各40例。两组均采用抗癫痫药物治疗,在此基础上对照组采用常规护理干预,研究组在对照组的基础上给予基于IMB模型的护理延伸服务。比较两组的干预效果。结果出院后2个月,研究组的癫痫持续发作时长短于对照组,癫痫发作次数少于对照组,差异具有统计意义(P<0.05)。出院后2个月,研究组的Morisky服药依从性量表(MMAS)、癫痫患者生存质量量表-31(QOLIE-31)评分高于对照组,差异具有统计学意义(P<0.05)。研究组的不良反应总发生率为5.00%,低于对照组的20.00%,差异具有统计学意义(P<0.05)。结论基于IMB模型的护理延伸服务可有效减少癫痫持续发作时长与发作次数,增强患者的服药依从性,减少不良反应发生率,提高患者的生活质量。

赋能理论模式护理对老年继发性癫痫患者自我管理能力和生活质量的影响

目的 分析老年继发性癫痫患者采用赋能理论模式护理的效果。方法 随机选取2022年1月—2023年1月潍坊市中医院收治的80例老年继发性癫痫患者为研究对象,根据不同护理方法将其分为对照组(n=40)和观察组(n=40)。对照组采用常规护理,观察组采用赋能理论模式护理。比较两组不良情绪评分[焦虑自评量表(Self-rating Anxiety Scale, SAS)、抑郁自评量表(Self-rating Depression Scale, SDS)]、自我管理能力评分、生活质量评分[中文版癫痫患者生活质量评定量表-31(Epileptic Quality Of Life Eating Scale, QOLIE-31)]及病耻感[中文版病耻感量表(Mental Illness Stigma Scale-Chinese, SSMI-C)]和护理满意度。结果 护理后,观察组SAS评分(44.21±3.02)分、SDS评分(43.21±3.61)分低于对照组的(49.97±4.81)分和(48.35±4.44)分,差异有统计学意义(t=6.414、5.680,P均<0.05)。护理后,两组自我管理能力评分升高,且观察组高于对照组,差异有统计学意义(P均<0.05)。护理后,两组SSMI-C评分降低,QOLIE-31评分升高,且观察组优于对照组,差异有统计学意义(P均<0.05)。观察组护理满意度为95.00%(38/40),高于对照组的75.00%(30/40),差异有统计学意义(χ^(2)=6.274,P=0.012)。结论 赋能理论模式护理干预对老年继发性癫痫患者不良情绪的缓解作用显著,可提高其自我管理能力,降低病耻感,提升患者的生活质量,护理满意度较高。

柴胡皂甙a减轻戊四氮诱发的皮质酮抑郁模型小鼠的急性癫痫发作:基于小胶质细胞介导的炎症反应

目的探讨柴胡皂甙a(SSa)对皮质酮(CORT)抑郁模型基础上诱发小鼠急性癫痫的干预作用及机制。方法选用雄性SPF C57BL/6J小鼠,使用皮质酮口服给药,制备CORT抑郁模型,之后予戊四氮诱发小鼠急性癫痫发作,并腹腔注射柴胡皂苷a进行干预。根据干预方式的不同将小鼠分成对照组、Epilepsy组、Epilepsy+SSa组、CORT+Epilepsy、CORT+Epilepsy+SSa组,6只/组。利用旷场实验、十字高架实验、强迫游泳实验、糖水偏好实验评估抑郁相关指标,通过ELISA实验检测血皮质酮含量;采用痫性发作分级、海马形态学评估癫痫发作程度;RT-qPCR检测炎症相关因子、免疫荧光实验观察小胶质细胞活化情况。结果成功构建皮质酮诱导的小鼠抑郁模型,小鼠的体质量、糖水偏好率、旷场的总路程、中央格停留时间和路程、开放臂进入次数和开放臂停留时间百分比均降低(P<0.05),强迫游泳不动时间和血清CORT含量增加(P<0.05);与Epilepsy组相比,CORT+Epilepsy组小鼠痫性发作潜伏期缩短,发作次数、发作等级以及发作持续时间都明显增加(P<0.05),海马CA1、CA3区神经元Nissl体表达减少,Iba1阳性细胞的数量增多,同时,海马中IL-1β、IL-10、TNF-α、IFN-γ的表达水平升高。SSa干预后,Epilepsy+SSa组和CORT+Epilepsy+SSa组的癫痫发作潜伏期均延长,发作次数、发作持续时间、发作级别均减少(P<0.05),海马CA1、CA3区神经元的Nissl小体数量均增加、Iba1阳性细胞的数量均有所减少,海马中IL-1β、IL-10、TNF-α、IFN-γ的表达水平均降低(P<0.05)。结论抑郁状态加重了癫痫发作、小胶质细胞活化及炎症水平更高,而柴胡皂甙a可能通过调节小胶质细胞介导的炎症激活,减轻抑郁合并癫痫小鼠的发作。

病毒性脑炎217例症状性癫痫发生风险的预测研究

目的分析病毒性脑炎并发症状性癫痫的风险因素,据此构建列线图预测模型。方法回顾性分析2018年2月至2022年5月汕头市中心医院收治的217例病毒性脑炎病人临床资料,抽取70%为建模集(152例),30%为验证集(65例)。根据病人是否合并症状性癫痫,将建模集进一步分为发生组和未发生组,比较两组病人一般资料,选择差异有统计学意义的指标用逐步向前回归法进行非条件多因素logistic分析病毒性脑炎病人症状性癫痫发生的影响因素,并采用R3.4.3软件包绘制基于多因素分析结果的列线图模型。采用Bootstrap法分别对建模集和验证集进行验证,并绘制受试者操作特征曲线(ROC曲线)和决策曲线(DCA)以评估列线图模型的预测效能和临床净获益率。结果217例病毒性脑炎病人中,共46例病人合并症状性癫痫(21.20%),其中建模集中有32例合并症状性癫痫,验证集中有14例合并症状性癫痫;发生组昏迷、大脑皮质损坏、脑电图重度异常、颅脑核磁共振成像(MRI)有责任病灶、累及颞叶或额叶、脑脊液单纯疱疹病毒(HSV)(+)占比及脑脊液压力均高于未发生组(P<0.05);logistic多元回归分析,昏迷、大脑皮质损坏、脑电图重度异常、颅脑MRI有责任病灶、累及颞叶或额叶、脑脊液压力、脑脊液HSV(+)均是病毒性脑炎合并症状性癫痫的影响因素(P<0.05);经Bootsrap法进行验证,建模集其一致性指数(C-index)为0.833,验证集的C-index则为0.830,校正曲线和标准曲线拟合度较好。建模集ROC曲线下面积(AUC)、灵敏度、特异度分别为0.84[98%CI:(0.78,0.89)]、79.17%、84.04%,验证集则为0.81[98%CI:(0.76,0.86)],83.04%,73.64%,提示模型区分度良好。DCA曲线显示病人根据列线图模型进行风险评估可获得满意的净收益。结论昏迷、大脑皮质损坏、脑电图重度异常、颅脑MRI有责任病灶、累及颞叶或额叶、脑脊液压力、脑脊液HSV(+)均是病毒性脑炎合并症状性癫痫的影响因素,综合上述因素针对病毒性脑炎病人构建的列线图预测模型可以较好地个体化预测症状性癫痫的发生,对临床防治症状性癫痫提供指导。

跨理论模型护理方案对老年癫痫病人疲劳感和心理健康的干预效果

目的探讨跨理论模型(行为分阶段转换理论)(TTM)护理干预对老年癫痫病人疲劳感和负性情绪的影响。方法选择2022年1月至2023年3月住院治疗的老年癫痫病人95例,采用TTM进行护理干预。比较干预前后病人焦虑自评量表(SAS)、抑郁自评量表(SDS)、疲乏修订量表(RPFS)评分以及TTM阶段期变化、TTM阶段期改变跨度、病人对癫痫药物的了解程度和发作自救掌握程度等评估结果。结果经过3个月的行为干预护理,病人SAS、SDS、RPFS得分,TTM行为阶段改变期和改变期跨度,自评项目和药物知识掌握度等均明显优于干预前,差异具有统计学意义(P<0.05)。结论运用TTM对老年癫痫病人进行护理干预,不仅改善了病人的健康行为,提高了病人对疾病知识的掌握程度,同时也降低了病人的焦虑、抑郁情绪和疲劳感。

海人藻酸建立内侧颞叶癫痫小鼠模型的研究

目的 本研究采用立体定向手术在一侧海马注射海人藻酸(kainic acid, KA),建立内侧颞叶癫痫(medial temporal lobe epilepsy, MTLE)慢性模型,通过行为学、电生理学和病理学验证其有效性。方法 取健康的C57BL/6野生型雄鼠22只,随机分成对照组(n=6)和实验组即KA注射组(n=16)。对照组和实验组分别在海马CA3区进行微量注射生理盐水和KA,1周后再次进行立体定向手术,植入脑电记录电极。植入术后1周开始记录小鼠脑电活动,统计癫痫发作次数和持续时间。通过对小鼠的观察与记录,分别从行为学、电生理学和病理学方面验证慢性癫痫模型。结果 本实验对22只C57BL/6野生型雄鼠进行实验,对照组均无癫痫发作,而实验组存活的小鼠均出现癫痫发作。成模的小鼠在行为学上发生了凝视、咀嚼、头面部肌肉抽搐、肢体痉挛等慢性癫痫自发发作行为,有2只小鼠因手术死亡、4只小鼠在急性发作期死亡、10只小鼠模型成功建立;脑电图呈内侧颞叶癫痫样脑电图改变;在病理组织学方面,经免疫荧光染色发现:CA3区神经元丢失,星形胶质细胞大量增生,符合海马硬化特征性的病理改变。结论 通过使用KA单侧、单次颅内注射构建的模型具有耗时、易操作、易成型等多项优势,该模型展现出与人类MTLE相似的脑电图、行为与神经病理改变,有助于研究治疗颞叶癫痫的药物,是癫痫外科手术预后判断的理想动物模型。

基于中西医临床病症特点的难治性癫痫动物模型评价与分析

目的基于难治性癫痫的中西医临床病症特点,对比评估现有难治性癫痫动物模型,评价模型的有效性和局限性,并探讨整合中西医理论、优化模型构建的思路,为难治性癫痫的机制阐明和防治提供新的研究方向。方法通过查阅相关文献,整理分析相关资料,总结现有难治性癫痫动物模型复制方法、动物品系和模型优缺点,以难治性癫痫的西医诊断标准与中医辨证标准为依据,对现有的动物模型与临床症状的吻合度进行分析和评价。结果总结现有的难治性癫痫动物模型,发现电点燃和化学点燃是目前常用的造模方法,锂-匹罗卡品模型和海马内海人酸模型与中西医临床病症特点吻合度较高,是目前应用较广泛的动物模型。现有模型多侧重于模拟难治性癫痫的病理改变,而对于中医学所重视的先天禀赋、情志失调等因素考虑不足,因此在模拟难治性癫痫的病因复杂性、临床异质性和药物治疗反应性等方面仍存在一定局限。结论复制动物模型虽然可以在一定程度上反映其发病机制,但与机体的自然发病状态和临床表现仍然有较大差异。现有难治性癫痫动物模型多采用电刺激或化学药物诱导,在模拟癫痫持续状态、耐药性方面有一定优势,但仍存在诱导方法单一、病理改变不够复杂等局限。未来可尝试整合中医辨证分型与常规的电刺激或化学药物诱导方法,通过模拟多种致病因素,建立涵盖不同中医证型的难治性癫痫动物模型。同时,采用行为学、电生理、影像学和组织病理学等多维度指标,构建更全面的评价体系,以提高模型的临床相关性和转化应用价值。在造模过程中,可通过夹尾法、慢性束缚法、颈部带枷单笼喂养法等方式建立肝郁证模型;采用高脂饲料喂饲法建立痰凝证模型;使用夹尾+肾上腺素注射的方法建立气滞血瘀证模型;应用惊恐伤肾结合劳倦游泳建立肾虚精亏证模型等。还可通过改变光照和温度条件,模拟环境中的阴阳变化,研究环境变化对中医动物模型的影响。为难治性癫痫的治疗与研究提供更多思路。

关于ILAE/AES联合报告“重新审视耐药性癫痫概念”的解读

尽管新型抗癫痫药物(ASMs)不断涌现,目前已经发展到第三代,但仍有1/3癫痫患者可发展为耐药性癫痫(DRE)。早在2010年,国际抗癫痫联盟(ILAE)就提出了DRE概念并沿用至今,及早诊断DRE,有助于对ASMs无反应的个体进行术前评估,并从癫痫外科手术中受益。由于DRE的发病率仍然很高以及概念一直没有更新,故在2023年8月ILAE/美国癫痫协会(AES)联合工作组从协调临床前和临床研究角度出发,在整个生命周期和跨物种基础上讨论了DRE表现和机制的异质性、复杂性及动态变化。联合工作组建议有必要重新审视DRE的当前定义,以更好地服务DRE临床管理以及指引DRE未来研究方向,为患者筛选更有效、更精准的个体化治疗,以减少DRE发病率,提高患者生活质量。本文旨在就ILAE/AES此份报告做一简要介绍和解读。

儿童药物难治性癫痫预后危险因素及回归预测模型构建与评价

目的探讨儿童药物难治性癫痫(DRE)预后危险因素,建立回归预测模型,为癫痫患儿预后判断及后续治疗方案制定提供指导。方法选取人民解放军联勤保障部队第904医院儿科2019年1月至2022年1月接诊的126例DRE儿童,均接受药物调整治疗,依据治疗后1年癫痫控制情况分为预后良好组、预后不良组。对DRE患儿预后不良的可能影响因素进行单因素分析,再通过Logistic回归模型明确患儿预后不良的独立影响因素;构建回归预测模型,应用H-L检验评价回归模型拟合优度,受试者工作特征曲线(ROC)观察回归模型预测效力。结果126例DRE患儿中预后良好72例(57.14%),归为预后良好组;预后不良54例(42.86%),归为预后不良组。单因素分析可知,两组患儿起病年龄、病因、治疗前发作频率、智能障碍、头颅MRI、本次治疗抗癫痫药物(AEDs)用药种类比较,差异有统计学意义(P<0.05)。Logistic回归分析显示,起病年龄为DRE患儿预后不良的独立保护因素(OR=0.318),病因、治疗前发作频率、智能障碍为独立危险因素(OR分别为3.271、5.581、4.361)(P<0.05)。依据独立影响因素的回归系数构建Logistic回归预测模型,H-L检验显示,χ^(2)=8.600,DF=8,P=0.377,提示模型拟合优度良好,构建有效。ROC曲线显示,模型预测DRE患儿预后不良的AUC为0.828,95%CI为0.754~0.902,P<0.001,提示模型预测效力中等。约登指数取最大值0.569时,模型预测敏感度为72.22%,特异度为84.72%。结论本研究构建的回归预测模型可为DRE患儿预后判断提供参考,有利于个性化治疗与管理。

Epileptic brain network mechanisms and neuroimaging techniques for the brain network

Epilepsy can be defined as a dysfunction of the brain network,and each type of epilepsy involves different brain-network changes that are implicated diffe rently in the control and propagation of interictal or ictal discharges.Gaining more detailed information on brain network alterations can help us to further understand the mechanisms of epilepsy and pave the way for brain network-based precise therapeutic approaches in clinical practice.An increasing number of advanced neuroimaging techniques and electrophysiological techniques such as diffusion tensor imaging-based fiber tra ctography,diffusion kurtosis imaging-based fiber tractography,fiber ball imagingbased tra ctography,electroencephalography,functional magnetic resonance imaging,magnetoencephalography,positron emission tomography,molecular imaging,and functional ultrasound imaging have been extensively used to delineate epileptic networks.In this review,we summarize the relevant neuroimaging and neuroelectrophysiological techniques for assessing structural and functional brain networks in patients with epilepsy,and extensively analyze the imaging mechanisms,advantages,limitations,and clinical application ranges of each technique.A greater focus on emerging advanced technologies,new data analysis software,a combination of multiple techniques,and the construction of personalized virtual epilepsy models can provide a theoretical basis to better understand the brain network mechanisms of epilepsy and make surgical decisions.

难治性癫痫患者术后复发的危险因素分析及风险预测模型构建

目的探讨难治性癫痫患者术后复发的危险因素并构建预测模型。方法回顾性收集2021年6月—2022年10月在本院接受外科手术治疗的280例难治性癫痫患者的临床资料,术后均随访1年。根据复发情况分为未复发组238例和复发组42例。难治性癫痫患者术后复发的危险因素采用单因素、多因素Logistic回归分析法分析;绘制受试者工作特征(ROC)曲线分析预测模型对难治性癫痫患者术后复发的预测价值。结果多因素Logistic回归分析结果显示,病程>5年、术前病灶定位与手术部位不完全一致、血清维生素B6水平低、血清单核细胞趋化蛋白-1(MCP-1)水平高均是难治性癫痫术后复发的危险因素(OR=2.705、2.314、1.790、2.284,P<0.05)。构建回归模型并按照预测概率logit(P)绘制难治性癫痫术后复发的ROC曲线,当logit(P)>14.52时,曲线下面积(AUC)为0.850,敏感度为78.57%,特异度为80.67%。结论难治性癫痫患者经外科手术治疗后复发的危险因素包括病程>5年、术前病灶定位与手术部位不完全一致、血清维生素B6水平低、血清MCP-1水平高,据此构建的难治性癫痫术后复发的回归模型预测价值较高,可对术后复发的高危群体进行针对性干预,降低其复发风险。