常规治疗联合拉莫三嗪对儿童难治性癫痫生活质量的影响

【目的】探讨常规治疗联合拉莫三嗪对儿童难治性癫痫生活质量的影响。【方法】选取儿童难治性癫痫患者35例,其中复杂部分性发作8例,部分性发作继发全身性发作8例,全身性强直-阵挛性发作12例,Len-nox-Gaust综合征7例,采用常规治疗联合拉莫三嗪治疗,采用Mark等制定的儿童癫痫生活质量量表（QOLCE）对拉莫三嗪治疗前后生活质量进行评估和对比。【结果】常规治疗联合拉莫三嗪对各种儿童难治性癫痫均有效,总有效率51．4％,尤其是对Lennox-Gaust综合征疗效最显著;治疗后患者生活质量较添加治疗前明显提高（ P＜0．05）,尤其是认知功能和社会功能方面改善显著（ P ＜0．01）;无明显不良反应。【结论】常规治疗联合拉莫三嗪治疗能明显改善儿童难治性癫痫患者的生活质量,安全性良好。     

丙戊酸钠联合拉莫三嗪应用于难治性癫痫治疗中的效果观察

目的探讨难治性癫痫治疗中应用丙戊酸钠联合拉莫三嗪治疗的效果。方法对2012年1月～2017年12月我院神经内科收治的50例难治性癫痫患者实施研究,按随机数表法分为单一组和联合组各25例,对单一组患者单用丙戊酸钠治疗,对联合组患者实施丙戊酸钠联合拉莫三嗪治疗,分析患者的疗效及安全性。结果联合组治疗总有效率明显高于单一组(P0.05);联合组治疗后癫痫发作频率低于单一组(P0.05),联合组用药不良反应发生率与单一组比较,无显著性差异(P0.05)。结论对难治性癫痫应用丙戊酸钠联合拉莫三嗪治疗的效果良好,且安全性高。     

拉莫三嗪联合丙戊酸钠治疗难治性癫痫的效果观察

目的研究拉莫三嗪联合丙戊酸钠治疗难治性癫痫的临床效果。方法选取2016年1月至2017年12月难治性癫痫患者54例,依据治疗方案将其分为两组,每组27例。对照组患者行丙戊酸钠常规治疗,治疗组患者行拉莫三嗪联合丙戊酸钠治疗,对比两组疗效。结果治疗组治疗有效率为96.30%,高于对照组的77.78%,治疗后,治疗组发作次数、发作持续时间、癫痫样放电、累及导联数水平优于对照组,治疗3个月及6个月后,治疗组MMSE评分低于对照组,治疗组不良反应发生率为11.11%,低于对照组的37.04%,差异有统计学意义(P0.05)。结论拉莫三嗪联合丙戊酸钠治疗难治性癫痫,可有效提升治疗效率,改善临床症状,减少不良反应,疗效较优。     

拉莫三嗪对难治性部分性癫痫的疗效观察

观察拉莫三嗪对儿童期难治性部分性癫痫的疗效。方法将６３例患儿随机分为治疗组和对照级,随访观察６个月,比较治疗开始前和结束时的发作次数。结果治疗组缓解率,良效率明显高于对照组,差异非常显著,结论拉莫三嗪对儿童难治性部分性癫痫有良好疗效,并可推广应用于其它类型的癫痫。     

拉莫三嗪和丙戊酸钠联合治疗儿童难治性癫痫自身对照研究

目的 了解丙戊酸钠和拉莫三嗪联合治疗儿童难治性癫痫的疗效及安全性.方法 收集难治性儿童癫痫21例,已用丙戊酸钠者,停用其它抗癫痫药,从0.1 5mg/(kg·d)每日一次开始添加拉莫三嗪,第.一月每周增加O.2mg/(kg·d),随后每周0.3mg/(kg·d),直至发作控制或6mg/(kg·d).原来未用丙戊酸钠者,先加丙戊酸钠根据血药浓度调整至有效范围,再减停其它抗癫痫药物,同样方法加用拉莫三嗪.结果 全而性癫痫10例,部分性癫痫l]例.2种发作形式以上占9例(42.9%).可能病因9例(42.9%),头颅影像学异常6例(28.6%).10例(47.7%)完全控制,6例(28.6%)有效,5例(23.8%)无效,治疗前后发作频率减少有显著性差异(Jp＜0.001).治疗9月后5例(7.8%)脑电图恢复正常.8例(38.1%)出现不良反应.结论 拉莫三嗪和丙戊酸钠联合应用为一种有效、安全而经济的治疗小儿难治性癫痫的方法.     

拉莫三嗪治疗儿童难治性癫痫的临床效果及安全性观察

目的观察拉莫三嗪(LTG)治疗儿童难治性癫痫的临床效果及安全性。方法选择同期难治性癫痫患儿70例,在患儿家长知情自愿的情况下分为对照组和观察组各35例,对照组给予丙戊酸钠治疗,观察组加用拉莫三嗪(LTG)治疗,比较两组治疗后发作频率及安全性。结果治疗3、6个月后,两组患儿癫痫每月发作频率比较,差异均具有统计学意义(P0.05);治疗期间两组不良反比较,差异无统计学意义(P0.05)。结论药物治疗儿童难治性癫痫时应加用LTG,可促进患儿的恢复、提高临床疗效,且安全可靠。     

拉莫三嗪治疗双相障碍躁狂发作74例

拉莫三嗪（利必通）在2001年被美国癫痫专家委员会（FDA）推荐为一线抗癫痫药物，2003年又被FDA批准作为双相情感障碍的维持治疗药物。目前应用拉莫三嗪治疗双相情感障碍躁狂发作的文献报道较少，本研究旨在验证拉莫三嗪治疗双相情感障碍躁狂发作的疗效及安全性。     

拉莫三嗪添加-替换治疗丙戊酸治疗无效的癫痫患者的临床疗效

目的探讨拉莫三嗪添加-替换疗法在丙戊酸治疗无效癫痫中的应用效果。方法将90例丙戊酸治疗无效癫痫患者随机分为对照组和治疗组各45例,对照组应用单用拉莫三嗪,治疗组以拉莫三嗪添加-替换丙戊酸进行治疗,对比两组的治疗效果。结果治疗后,两组的癫痫发作频率、发作时间均有明显改善,并且治疗组治疗后的癫痫发作频率明显低于对照组,每次发作时间明显短于对照组(P0.05);治疗组的治疗总有效率为88.89%,显著高于对照组的62.22%(P0.05);两组的不良反应发生率比较无显著性差异(P0.05)。结论对丙戊酸治疗无效癫痫患者应用拉莫三嗪进行添加-替代治疗,能有效提高临床疗效,且不会增加不良反应,是一种安全有效的治疗方案。     

小剂量丙戊酸联合拉莫三嗪对癫痫患者症状改善及不良反应发生率的影响

目的探究小剂量丙戊酸联合拉莫三嗪对癫痫患者症状改善及不良反应发生率的影响。方法选取2015年1月~2016年5月我院74例癫痫患者,按照随机抽签方式进行分组,对照组37例予以丙戊酸治疗,观察组37例采用小剂量丙戊酸联合拉莫三嗪治疗,观察比较两组临床疗效及不良反应发生率,并统计两组治疗前后症状(发作次数、发作持续时间、累及导联数与癫痫放电)改善情况。结果治疗后观察组总有效率94.59%高于对照组75.68%,发作持续时间、发作次数、累及导联数与癫痫放电均低于对照组,不良反应发生率10.81%低于对照组40.54%,差异具有统计学意义(P0.05)。结论小剂量丙戊酸联合拉莫三嗪治疗癫痫患者疗效显著,改善患者临床症状,降低不良反应发生率。     

拉莫三嗪添加-替换治疗丙戊酸治疗无效的 癫痫患者的疗效

目的:探讨丙戊酸治疗无效的癫痫患者采用拉莫三嗪添加-替换治疗的疗效。方法:丙戊酸治疗无效的癫痫患者100例,随机分为对照组和观察组各50例,对照组给予拉莫三嗪单独用药治疗,观察组给予拉莫三嗪与丙戊酸联合用药治疗,分析2组治疗有效率、治疗前后发作次数、每次持续时间、血药浓度以及不良反应发生率。结果:与对照组相比,观察组的总有效率高于对照组,不良反应发生率低于对照组,治疗后发作次数和每次发作持续时间低于对照组,血药浓度高于对照组,差异均有统计学意义(P0.05)。结论:对于丙戊酸治疗无效的癫痫患者采用拉莫三嗪添加-替换治疗可提升疗效。     

Clinical pharmacology and therapeutic use of the new antiepileptic drugs

Although older generation antiepileptic drugs (AEDs) such as carbamazepine, phenytoin and valproic acid continue to be widely used in the treatment of epilepsy, these drugs have important shortcomings such as a highly variable and nonlinear pharmacokinetics, a narrow therapeutic index, suboptimal response rates, and a propensity to cause significant adverse effects and drug interactions. In an attempt to overcome these problems, a new generation of AEDs has been introduced in the last decade. Compared with older agents, some of these drugs offer appreciable advantages in terms of less variable kinetics and, particularly in the case of gabapentin, levetiracetam and vigabatrin, a lower interaction potential. Lamotrigine, topiramate, zonisamide and felbamate protect against partial seizures and a variety of generalized seizure types, vigabatrin is effective against partial seizures (with or without secondary generalization) and infantile spasms, while the use of oxcarbazepine, tiagabine and gabapentin is mainly restricted to patients with partial epilepsy (and, in the case of oxcarbazepine, also primarily generalized tonic-clonic seizures). Levetiracetam, the latest AED to be introduced, has been found to be effective in partial seizures, but its potentially broader efficacy spectrum remains to be determined in clinical studies. Currently, the main use of new generation AEDs is in the adjunctive therapy of patients refractory to older agents. However, due to advantages in terms of tolerability and ease of use, some of these drugs are increasingly used for first-line management in certain subgroups of patients. Due to serious toxicity risks, felbamate and vigabatrin should be prescribed only in patients refractory to other drugs. In the case of vigabatrin, however, first line use may be justified in infants with spasms.     

三步法定位并多术式联用显微外科手术治疗难治性癫痫

目的探讨难治性癫痫致痫灶定位和手术治疗方法。方法对81例难治性癫痫患者综合运用临床症状学、神经电生理、高场强MRI、PET/CT、术前及术中皮层及深部电极等三步法定位致痫灶,单纯病灶切除、病灶切除加胼胝体切开、病灶切除加软膜下横切、病灶切除加单脑回灰白质联合切除等多术式联用切除致痫灶和/或阻断传导通路。结果三步法致痫灶定侧准确率100%。多术式联用治疗后,满意31例,显著改善17例,良好16例,效差14例,无改善3例,总有效率79.0%。结论三步法可以对致痫灶精确定位,多术式联合处理致痫灶或/和传导通路可以取得良好的疗效。     

丙戊酸钠联合氯硝西泮治疗难治性癫痫的疗效观察

目的 观察丙戊酸钠联合氯硝西泮治疗难治性癫痫的临床疗效及不良反应.方法 125例难治性癫痫患者随机分为两组,治疗组(n=65)采用丙戊酸钠联合氯硝西泮治疗,对照组(n=60)采用苯妥英钠治疗,两组疗程均为6个月,观察两组治疗总有效率及治疗期间不良反应情况.结果 治疗组总有效率(89.2%)明显高于对照组(78.3%)(P<0.05),两组治疗过程中未出现严重不良反应.结论 丙戊酸钠联合氯硝西沣治疗难治性癫痫疗效显著,不良反应少,值得临床推广应用.     

氯巴占治疗难治性癫痫专家共识(2022)

多数癫痫患者经规范化抗癫痫治疗后,症状可得到良好控制或缓解,但30%～40%患者经长期药物干预后,仍反复出现癫痫发作,进展为难治性癫痫。Lennox-Gastaut综合征、Dravet综合征和肌阵挛-失张力癫痫均为儿童期起病的难治性癫痫,严重威胁患者的身心健康。2011年美国食品药品监督管理局批准氯巴占用于年龄≥2岁Lennox-Gastaut综合征患者癫痫发作的辅助治疗,且该药品在Dravet综合征和肌阵挛-失张力癫痫的治疗中也有一定应用。目前,氯巴占的药理作用机制尚未完全明确,可能通过与γ-氨基丁酸A受体上的苯二氮艹卓类位点相结合发挥药理作用。在体内,氯巴占和N-去甲氯巴占主要经CYP3A4、CYP2C19代谢,临床应用时需警惕与其他药物的相互作用。对于CYP2C19慢代谢患者,还应关注N-去甲氯巴占的血药浓度,并监测药物相关不良反应。为促进氯巴占在我国临床应用的进一步规范化,保障临床用药的有效性和安全性,北京协和医院罕见病多学科协作组联合中国罕见病联盟,组织相关领域专家,经多次讨论、修改,最终制定了本共识,以供临床参考。     

维拉帕米对难治性癫大鼠的疗效及海马P-糖蛋白表达的影响

目的:观察耐药蛋白抑制剂维拉帕米对难治性癫大鼠的疗效及海马P-糖蛋白表达的影响。方法:Wistar大鼠50只,随机分为生理盐水组(NS组)、匹罗卡品组(PILO组)、卡马西平组(CBZ组)、低剂量维拉帕米组(LDV组)和高剂量维拉帕米组(HDV组),氯化锂-匹罗卡品腹腔注射制作大鼠自发性癫模型,选择耐药癫大鼠,分别给予常规或添加维拉帕米抗癫治疗,观察大鼠性发作频率及海马P-糖蛋白表达的变化。结果:与NS组相比,其它4组大鼠性发作频率增高,海马P-糖蛋白表达增强(P0.05);LDV组和HDV组大鼠的性发作频率及海马P-糖蛋白表达较PILO组和CBZ组降低(P0.05);PILO组和CBZ组大鼠性发作频率及海马P-糖蛋白表达无明显差异,LDV组和HDV组大鼠性发作频率及海马P-糖蛋白表达无明显差异。结论:添加维拉帕米治疗可明显减少难治性癫大鼠性发作频率,降低难治性癫大鼠海马P-糖蛋白的表达。     

Review of Transcranial Magnetic Stimulation in Epilepsy

PurposeDespite the availability of numerous pharmacologic and nonpharmacologic antiseizure therapies, a fraction of patients with epilepsy remain refractory to current treatment options, underscoring the need for novel drugs and neuromodulatory therapies. Transcranial magnetic stimulation (TMS), coupled with either electromyography or electroencephalography, enables rapid measurement of the cortical excitation/inhibition ratio, which is pathologically shifted toward excess excitability in patients with epilepsy. In this review, we summarize: (1) TMS protocols that have been deployed to identify promising compounds in the antiepilepsy drug (AED)-development pipeline, and (2) the therapeutic potential of TMS in the treatment of drug-resistant seizures.MethodsA focused literature review of the use of TMS in epilepsy, using a PubMed search, was performed. Over 70 articles were included that pertained to: (1) the use of TMS-EMG and TMS-EEG in elucidating the mechanisms of action of AEDs and in discovering potential new AEDs; and (2) the use of repetitive TMS in the treatment of seizures.FindingsStudies from the literature have reported that AEDs alter TMS-derived metrics, typically by leading to a net increase in cortical inhibition with successful therapy. Preclinical TMS work in rodent models of epilepsy has led to the development of novel antiseizure drug compounds. Clinical translational studies of TMS have been used to determine guidelines on the dosages of other agents in the AED pipeline in preparation for clinical trials. Several studies have described the use of therapeutic repetitive TMS in both the ictal and interictal states of epilepsy, with inconsistent results.ImplicationsTMS has diagnostic and therapeutic potential in epilepsy. TMS-derived markers can enable early-stage measures of AED target engagement, and can facilitate studies of the pharmacokinetic and pharmacodynamic properties of AEDs. TMS may also be used in the early prediction of the efficacy of different AEDs in treating patients, and in direct neuromodulation of epileptic networks. From the therapeutics perspective, despite favorable results in some trials, the optimization of treatment paradigms and the determination of ideal candidates for TMS are still needed. Finally, preclinical experiments of TMS have provided mechanistic insight into its effects on the excitation/inhibition ratio, and may facilitate rational drug–device coupling paradigms. Overall, the capacity of TMS in both the modulation and measurement of changes in cortical excitability highlights its unique role in advancing antiepilepsy therapeutics     

普罗加比治疗难治性癫痫有效性及安全性的Meta分析

目的系统评价普罗加比(progabide,PGB)治疗难治性癫痫的有效性及安全性。方法计算机检索PubMed、EMbase、e Cochrane Central Register of Controlled Trial(s CENTRAL)、CNKI、VIP和CBM等电子数据库,查找PGB治疗难治性癫痫的随机对照试验(RCT),检索时间均从建库至2011年7月。对符合纳入标准的RCT,由两位评价员按Cochrane系统评价的方法,独立进行资料提取、质量评价并交叉核对后,采用RevMan 5.1软件进行Meta分析。结果共纳入7个研究,合计231例患者。Meta分析结果显示,在常规治疗基础上,与安慰剂相比,PGB对单纯难治性部分性癫痫无效[OR=1.76,95%CI(0.40,7.65),P=0.45];对难治性部分性+全面性癫痫的有效率高于安慰剂组[OR=4.46,95%CI(2.06,9.65),P=0.000 1]。PGB的主要不良反应为嗜睡、头晕、头痛等,但表现多轻微、短暂,减少剂量多可恢复正常,仅少数患者需停药。结论现有研究证据显示,PGB可能对难治性部分性+全面性癫痫具有较好的疗效,但对单纯性难治性癫痫的疗效尚不确定。PGB不良反应多轻微。但由于纳入研究的方法学质量存在中度选择性偏倚的可能性,可能影响结果的真实性,因此上述结论还有待开展更多高质量大样本的随机双盲临床对照试验来验证。     

A ketogenic diet suppresses seizures in mice through adenosine A₁ receptors

A ketogenic diet (KD) is a high-fat, low-carbohydrate metabolic regimen; its effectiveness in the treatment of refractory epilepsy suggests that the mechanisms underlying its anticonvulsive effects differ from those targeted by conventional antiepileptic drugs. Recently, KD and analogous metabolic strategies have shown therapeutic promise in other neurologic disorders, such as reducing brain injury, pain, and inflammation. Here, we have shown that KD can reduce seizures in mice by increasing activation of adenosine A1 receptors (A1Rs). When transgenic mice with spontaneous seizures caused by deficiency in adenosine metabolism or signaling were fed KD, seizures were nearly abolished if mice had intact A1Rs, were reduced if mice expressed reduced A1Rs, and were unaltered if mice lacked A1Rs. Seizures were restored by injecting either glucose (metabolic reversal) or an A1R antagonist (pharmacologic reversal). Western blot analysis demonstrated that the KD reduced adenosine kinase, the major adenosine-metabolizing enzyme. Importantly, hippocampal tissue resected from patients with medically intractable epilepsy demonstrated increased adenosine kinase. We therefore conclude that adenosine deficiency may be relevant to human epilepsy and that KD can reduce seizures by increasing A1R-mediated inhibition.     

Lamotrigine as a possible cause of QRS prolongation in a patient with known seizure disorder

Lamotrigine and felbamate are 2 newer anticonvulsant medications used to control refractory partial and generalized seizures. Although several cases of lamotrigine toxicity secondary to acute intentional or unintentional overdose have been described, there is little published information related to potential side-effects associated with the therapeutic use of these agents. Described is a case of a 22-year-old woman who presented to the emergency department after experiencing 2 seizure-like episodes. Findings on evaluation included nystagmus, ataxia, widening of the QRS complex and right-axis deviation on ECG. The patient reported only therapeutic use of her medications. The lamotrigine level was 14.8 mg/L. The mechanism of action for lamotrigine is blockade of the sodium channels; therefore, the patient was treated with intravenous sodium bicarbonate with resultant QRS narrowing following administration.     

Seizure suppression by GDNF gene therapy in animal models of epilepsy.

Temporal lobe epilepsy patients remain refractory to available anti-epileptic drugs in 30% of cases, indicating a need for novel therapeutic strategies. In this context, glial cell line-derived neurotrophic factor (GDNF) emerges as a possible new agent for epilepsy treatment. However, a limited number of studies, use of different epilepsy models, and different methods of GDNF delivery preclude understanding of the mechanisms for the seizure-suppressant action of GDNF. Here we show that recombinant adeno-associated viral (rAAV) vector-based GDNF overexpression in the rat hippocampus suppresses seizures in two models of temporal lobe epilepsy. First, when rAAV-GDNF was injected before hippocampal kindling, the number of generalized seizures decreased, and the prolongation of behavioral convulsions in fully kindled animals was prevented. Second, injection of rAAV-GDNF after kindling increased the seizure induction threshold. Third, rAAV-GDNF decreased the frequency of generalized seizures during the self-sustained phase of status epilepticus. Our data demonstrate the complexity of mechanisms and the beneficial action of GDNF in epilepsy. Furthermore, we show that ectopic rAAV-mediated GDNF gene expression in the seizure focus is a feasible way to mitigate seizures and provides proof of principle that the neurotrophic factor-based gene therapy approach has the potential to be developed as alternative strategy for epilepsy treatment.