抗癫痫药物对癫痫患者甲状腺激素水平影响的研究

目的 研究癫痫患者甲状腺激素水平和抗癫痫药物对其影响以及与疗效之间的关系。方法 测定已确诊的45例未服用过抗癫痫药物的癫痫患者血清甲状腺激素水平并与30例健康对照组进行比较。再经卡马西平、苯妥英钠、丙戊酸钠三种抗癫痫药物分组单药治疗3个月、6个月、年后观察甲状腺激素水平的变化及与疗效之间的关系。结果 未服用抗癫痫药物的新诊断癫痫患者游离甲状腺素（FT4）水平显著低于健康对照组,经苯妥英钠、卡马西平分别治疗3个月、6个月、1年后T4、FT4、FT3显著低于治疗前水平,TSH无显著性变化。经丙戊酸钠治疗后的不同时间段各甲状腺激素水平与治疗前比较无显著性差异（P＞0．05）。甲状腺激素水平的变化与化疗效之间似无相关性。结论 癫痫的反复发作虽未经抗癫痫药物治疗已存在FT4水平的降低。苯妥英钠、卡马西平可明显造成癫痫患者的亚临床甲状腺功能降低（T4、FT4、FT3下降）,丙戊酸钠对患者甲状腺激素水平无显著影响。甲状腺激素水平的变化与疗效之间无相关性。     

新型和传统抗癫痫药治疗新诊断癫痫患者的评价

目的评价新型和传统抗癫痫药(AEDs)单药治疗新诊断癫痫患者的疗效及安全性。方法前瞻性收集143例新诊断癫痫患者,分为卡马西平(CBZ)、丙戊酸钠(VPA)、托吡酯(TPM)和拉莫三嗪(LTG)治疗组,其中CBZ用于癫痫部分性发作,VPA用于癫痫全面性发作,而TPM和LTG用于各种类型癫痫发作,至少观察1年。采用生存分析Kaplan-Meier法比较治疗后癫痫初次发作时间、治疗失败时间,同时比较各组患者达"6月、1年无发作"比例和药物不良反应。结果 4组AEDs单药治疗后至癫痫初次发作时间、治疗失败时间的差异均无统计学意义(P0.05);CBZ、VPA、TPM和LTG组"6月无发作"率分别为80%、78%、87.9%、63.3%(均P0.05);"1年无发作"率分别为70%、66%、66.7%、50%(均P0.05)。TPM组不良反应率为63.3%,高于CBZ组(20%)、VPA组(24%)(均P0.01),而LTG组不良反应率为16.7%,与CBZ、VPA组相当(均P0.05)。结论从疗效和安全性综合考虑,新型AEDs治疗癫痫并不优于传统AEDs,其中TPM轻、中度不良反应还明显高于传统AEDs。     

抗癫痫药物引起的癫痫发作

抗癫痫药物引起的癫痫发作已受到广泛关注。本文讨论抗癫痫药物引起的癫痫发作机制,认为可能与药物中毒、药物的特异反应及药物的抗痫机制有关。本文还讨论了各种抗癫痫药引起癫痫发作的特点。     

癫痫患者使用抗癫痫药物对甲状腺激素的影响及其机理的进展

癫痫,抗癫痫药物,与甲状腺激素间的关系较复杂,目前普遍认为癫痫病人甲状腺激素降低是由某些抗癫痫药物所致。诱导肝酶的药物:卡马西平,苯妥因钠,苯巴比妥可致血甲状腺激素下降,非诱导肝酶的药物丙戊酸钠对甲状腺激素几乎无影响。其机理可能与下列因素有关:(1)诱导肝酶的抗癫痫药物诱导肝微粒体酶加速甲状腺激素的代谢。(2)下丘脑和/或垂体前叶功能受干扰。(3)抗癫痫药物对甲状腺的直接影响。本文还对甲状腺功能进行了探讨。     

抗癫痫药物对女性癫痫患者内分泌激素的影响

女性具有的生理特点及在社会中所承担的特殊角色给女性癫痫患者带来了更多需要特别关注的问题,尤其是内分泌问题。与正常女性相比癫痫患者更容易出现内分泌紊乱。现在的研究认为癫痫患者内分泌的变化与患者的癫痫发作类型、抗癫痫药物（AEDs）的使用均有密切联系。本文主要阐述AEDs对女性癫痫患者内分泌激素的影响,为临床上诊治女性癫痫患者和药物选择提供理论基础。     

育龄期女性癫痫患者抗癫痫药物使用的情况

目的探讨育龄期女性癫痫患者的抗癫痫药物使用情况。方法回顾性分析478例育龄期女性患者的药物使用情况。结果 478例患者中,332例患者使用单药治疗,其中133例(40.06%)使用拉莫三嗪,62例(18.67%)使用卡马西平,60例(18.07%)使用丙戊酸钠。96例(20.08%)两药联用,其中36例(32.73%)使用拉莫三嗪+丙戊酸钠。24例(5.02%)使用≥3种药物治疗。26例(5.44%)使用其他药物治疗。结论育龄期女性癫痫患者主要采用单药治疗,以拉莫三嗪为主。单药治疗效果不佳的患者中,以两药联用多见,以拉莫三嗪+丙戊酸钠为主。     

癫痫手术后患者抗癫痫药物应用策略

尽管神经电生理及影像学技术的应用提高了对脑内致痫源的识别和确定 ,手术方式的合理性及技巧性正得到进一步的改善 ,癫痫外科已成为难治性癫痫重要治疗手段之一 ,但手术对痫性发作控制的近期疗效和远期疗效因受到多种因素的制约 (如致痫病灶定位的精确度、癫痫的病因、痫性电活动的范围、病灶的可切除性等 )仍存在较大的变异。因此 ,患者术后抗癫痫药物 (AED)的管理仍是一项需要高度重视的工作。1　术后癫痫继续发作的高危因素 [1～ 3]癫痫外科治疗的理想结果是提高难治性癫痫患者的生活质量 ,达到临床完全无癫痫发作且无药物不良作用 ,…     

癫痫及抗癫痫药物与骨质疏松的研究进展

本文从癫痫本身和长期服用抗癫痫药物两方面综述了各自引起骨质疏松的原因及其可能的机制。其中包括:患者自身的生活、饮食等习惯、体内激素水平的紊乱甚至遗传因素。而长期服用某些抗癫痫药物的患者,药物在体内代谢过程中对某些代谢酶类及激素水平也有较大影响,从而影响骨质代谢,促进骨质疏松的发生。     

难治性癫痫术后抗癫痫药物的管理

难治性癫痫术后合理应用抗癫痫药物,是确保手术疗效和提高病人预后的重要因素。合理应用抗癫痫药物包括术后用药原则、何时减药、何时停药、及其注意事项。围手术期需要加大抗癫痫药物剂量,同时监测其血药浓度。预后评估较好的患者,术后无癫痫发作,1～2年可以停药。具有癫痫复发高危因素的患者,考虑长期服药。完全停药后不同年龄组的癫痫再发率不同,部分病人仍可以再次手术。     

癫痫特殊人群中抗癫痫发作药物的研究进展

<正>尽管存在多种治疗手段,但抗癫痫发作药物目前仍是治疗癫痫的主要手段。将抗癫痫发作药物与癫痫作为主题词,在PubMed数据库中进行检索,发现从2022-2023年3月,全球发表过2000多篇有关癫痫药物治疗的论文,表明抗癫痫发作药物治疗癫痫仍是癫痫学界的热点和前沿。而癫痫药物治疗中的孕妇、老年及儿童由于其生理状态不同,需要比普通人群更多的关注。     

新诊断癫痫患者药物治疗的长期结局及其影响因素

目的 探讨抗癫痫药物治疗新诊断癫痫患者的长期结局及影响长期结局的因素。方法 收集武汉大学人民医院癫痫库中2009年3月1日-2014年10月31日就诊的癫痫患者,回顾性分析患者在随访期间随时间而变化的药物反应(≥1、≥2、≥3年无发作率),并根据末次随访时是否达到至少3年无发作分为控制组和未控制组,探讨影响患者长期结局的临床因素; 对连续变量和分类变量分别采用t检验和卡方检验,采用单因素分析比较2组的临床资料,多元逻辑回归分析影响长期结局的因素。结果 本研究共纳入350例新诊断癫痫患者。1、2、3年无发作率分别为68.3%、61.1%、59.1%; 2年及3年无发作率明显低于1年无发作率(239/350,68.3% vs.214/350,61.1%,P=0.048)、(239/350,68.3% vs.207/350,59.1%,P=0.012),但2年和3年无发作率(214/350,61.1% vs.207/350,59.1%,P=0.589)无明显差异。其中至少3年无发作(控制组)207例(59.1%),未控制组143例(40.9%),单因素分析显示治疗期间有多种发作类型比只有一种发作类型的患者3年无发作率低(10/49,20.4% vs.197/301,65.4%,P<0.001)、有围产期损伤史的患者3年无发作率比无围产期损伤者要低(6/24,25.0% vs.201/326,61.7%,P<0.001)、多药治疗的患者比单药治疗的患者3年无发作率低(54/153,35.3% vs.153/197,77.7%,P<0.001)、早期6个月仍有发作的患者比早期6个月无发作的患者3年无发作率低(71/151,47.0% vs.136/199,68.3%, P<0.001); 进一步多因素回归分析发现治疗期间多种发作类型[优势比(OR)=4.054,95%置信区间(CI)=1.834～8.958,P=0.001]、多药治疗(OR=5.192,95%CI=2.911～9.261,P<0.001)和有围产期损伤史(OR=5.475,95%CI=1.924～15.580,P=0.001)是不能获得3年无发作的预测因素。结论 新诊断癫痫患者随着时间延长无发作率呈下降趋势,3年无发作率为59.1%; 多种发作类型、多药治疗、围产期损伤是影响新诊断癫痫患者药物治疗长期结局的独立危险因素。     

Pattern-reversal visual evoked potentials in patients with newly diagnosed epilepsy

PURPOSE: The possible occurrence of evoked potential (EP) abnormalities in patients with newly diagnosed epilepsy has been little investigated. The main purpose of the present study was to investigate possible changes in pattern-reversal visual evoked potential (P-VEP) responses in newly diagnosed epilepsy patients. METHODS: By using P-VEPs, latency values of the N75 and P100 together with amplitude values of P100 were recorded in newly diagnosed idiopathic epilepsy patients. The patients comprised two groups; nonphotosensitive (non-PS), and photosensitive (PS) patients. RESULTS: Shortened N75 and normal P100 latencies of the P-VEP with higher than normal P100 amplitudes were detected in PS patients. In non-PS patients, N75 latencies of the P-VEPs were unaffected; however, P100 latencies were prolonged, and P100 amplitudes were unchanged. CONCLUSIONS: P-VEPs are different from those of controls in previously untreated idiopathic epilepsy patients. Results also indicate different P-VEP features in patients with and without photoparoxysmal responses. The changes might be the result of a disorder of one or more neurotransmitters or subtle morphologic damage such as microdysgenesis.     

Proton magnetic resonance spectroscopic imaging studies in patients with newly diagnosed partial epilepsy

PURPOSE: To assess whether the N-acetyl aspartate (NAA) to creatine ratio (NAA/Cr) is abnormally low at the onset of epilepsy and whether successful treatment of seizures with antiepileptic drugs is sufficient for normalization of NAA/Cr. PATIENTS AND METHODS: Proton magnetic resonance spectroscopic imaging (1H-MRSI) was used to measure NAA/Cr in temporal lobes of eight patients with newly diagnosed epilepsy before or soon after starting medication. Six patients had follow-up 1H-MRSI examinations 7 months later. Clinical pattern of the seizures and the EEG findings suggested partial seizures in all and TLE in five patients. None of the patients had lesional epilepsy according to magnetic resonance imaging. RESULTS: Initial 1H-MRSI of the temporal lobes showed significantly low NAA/Cr values in five of eight patients. Five of six patients who had follow-up 1H-MRSI were seizure-free after using medication; the remaining patient did not take medication and continued to experience occasional auras. Wilcoxon rank sign comparison of NAA/Cr on initial 1H-MRSI examination and follow-up 1H-MRSIs showed no significant difference (Z = 135, p = 0.893, 2-tailed) for five seizure-free patients. CONCLUSIONS: Neuronal dysfunction is present at an early stage of the epileptic process. NAA/Cr recovery in seizure-free patients controlled with antiepileptic drugs is less evident, compared with successful surgical treatment. Thus, absence of seizures is not necessarily coupled with NAA/Cr improvement and observed variable response warrants further investigation.     

抗癫痫药对男性癫痫患者性激素的影响

用放免法测定２０例服用苯妥英钠（ＤＰＨ），２０例服用卡马西平（ＣＢＺ）的男性癫痫患者的血清性激素水平，包括总睾酮（ＴＴ）、游离睾酮（ＦＴ）和雌二醇（Ｅ２），并与１０例性功能正常男性和２３例未服药的癫痫男性患者对比。结果发现：ＤＰＨ引起ＴＴ和Ｅ２升高，ＣＢＺ则引起下降。说明两种抗癫痫药对性激素的影响机理不同，因而处理也不完全相同。     

单药阶梯式加量治疗新诊断成人癫痫的长期结局分析

目的探讨抗发作药物阶梯式加量治疗新诊断成人癫痫的长期结局及影响长期结局的临床因素。方法收集武汉大学人民医院癫痫库2009年3月1日-2016年12月31日就诊的新诊断成人癫痫患者,回顾性分析不同水平限定日剂量(Defined daily dose, DDD)单药治疗新诊断成人癫痫患者获得3年无发作的可能性,并探讨影响长期结局的临床因素。结果本研究共纳入316例新诊断成人癫痫患者,单药治疗3年无发作152例(48.1%),其中每日剂量≤25%DDD组(A组)9例、25%DDD<每日剂量≤50%DDD组(B组)89例、50%DDD<每日剂量≤75%DDD组(C组)44例、每日剂量>75%DDD组(D组)10例,3年无发作率分别为2.85%(9/316)、35.04%(89/254)、44.90%(44/98)和30.30%(10/33),B组3年无发作率明显高于A组(P=0.000),B组与C组3年无发作率无明显差异(P=0.088),C组与D组3年无发作率也无明显差异(P=0.142)。93.42%(142/152)的患者在75%DDD内获得3年无发作。单因素分析显示合...     

即刻和延迟治疗对新诊断癫痫患者复发的影响

目的 探讨不同治疗时机(即刻和延迟治疗)对新诊断癫痫患者复发的影响.方法 前瞻性收集新诊断癫痫患者的临床资料,根据治疗前发作次数将患者分为即刻治疗组(≤2次)及延迟治疗组(＞2次),给予合理抗癫痫药物治疗,至少观察2年.采用Kaplan-Meier统计分析比较2组患者治疗后至第1、2次复发的时间,同时比较治疗后不同随访时间点(3、6、12、24个月)的累计复发率.结果 共收集162例癫痫患者,其中即刻治疗组65例,延迟治疗组97例,随访2～14年(中位数3年).即刻治疗组治疗后至第1、2次复发时间均明显长于延迟治疗组,差异均有统计学意义(x2=5.94,P=0.020;x2=7.210,P=0.007).至随访终点,即刻治疗组有58.5%患者复发,低于延迟治疗组的72.2%,但差异没有统计学意义(x2=3.289,P=0.070).即刻治疗组和延迟治疗组治疗后3、6、12、24个月累计癫痫复发率分别为16.9%vs 35.1%、26.2%vs 48.5%、41.5%vs 56.7%、50.8%vs64.9%,仅在3、6月时差异均有统计学意义(x2=6.376,P=0.012;x2=8.098,P=0.004).结论 ≤2次癫痫发作后即刻给予合理抗癫痫药治疗可降低癫痫患者早期的复发风险.

Abstract：

Objective To explore the influences of immediate and deferred treatment with antiepileptic drugs (AEDs) on relapse of epilepsy in newly diagnosed patients. Methods The clinical data of newly diagnosed epileptic patients were collected prospectively and the patients were divided into immediate (seizures≤2) and deferred (seizures＞2) treatment groups according to times of seizures before treatment; these patients were treated with antiepileptic drugs reasonably. The patients were followed up for at least 2 years. Kaplan-Meier statistics was used to analyze the times to the first and second seizures after treatment. We also observed and compared their cumulative recurrence rate during the follow-up.Results One hundred and sixty-two patients were collected, 65 of which were in the immediate treatment group and 97 of which were in the deferred treatment group; The patients were followed up for 2-14 years(median 3 years). Times to the first and second seizures in the immediate treatment group were significantly longer than those in the deferred treatment group (x2=5.394, P=0.020; x2=7.210, P=0.007,respectively). Till the end of follow-up, 58.5% patients relapsed in the immediate treatment group, which was lower than that in the deferred treatment group (72.2%), but no statistical difference was noted (x2=3.289, P=0.07). The cumulative recurrence rates in the immediate and deferred treatment groups were 16.9% vs. 35.1% (x2=6.376, P=0.012), 26.2% vs. 48.5% (x2=8.098, P=0.004), 41.5% vs. 56.7% (x2=3.580,P=0.058) and 50.8% vs. 64.9% (x2=3.241, P=0.072) in the 3rd, 6th, 12th and 24th month of follow-up.Conclusion Immediate treatment with AEDs could reduce early recurrence rate of epilepsy in newly diagnosed epileptic patients with a few seizures (seizures ≤2).     

Patient-based assessments of quality of life in newly diagnosed epilepsy patients: validation of the NEWQOL

PURPOSE: In epilepsy, patient-based assessments are increasingly used as outcome measures in clinical trials of novel therapies alongside the traditional clinical measures of efficacy. The objective of this study was to validate psychometrically a quality of life (QOL) measure developed for use with recently diagnosed epilepsy patients. METHODS: The NEWQOL (Quality of Life in Newly Diagnosed Epilepsy Instrument) is a 93-item self-administered battery designed to assess QOL in patients with new-onset epilepsy. NEWQOL consists of eight multi-item scales (13 subscales) measuring several health parameters: Anxiety, Depression, Social Activities, Symptoms, Locus of Control/ Mastery, Neuropsychological Problems (includes the following subscales: Fatigue, Memory, Concentration, Motor Skills, and Reading), Social Stigma, Worry, Work Limitations, and several single-item measures (General Health, Number of Seizures, Social Limitations, Social Support, Self Concept, Ambition Limitations, Health Transition, and General Limitations). The NEWQOL was collected at baseline and 1 week post-baseline from 108 patients in the U.K. and U.S. RESULTS: All of the multi-item scales had high item discriminant validity, good test-retest reliability, and acceptable levels of internal consistency reliability; all but the Reading and Stigma subscales had negligible floor and ceiling effects. General linear models were used to examine the known groups validity of NEWQOL. Significant differences were observed in the Worry, Symptoms, Summary Neuropsychological Scales, and all Neuropsychological subscales (Memory, Fatigue, Concentration, Motor Skills, and Reading), indicating poorer functioning in the more frequent or severe seizure groups. CONCLUSIONS: Results from this study offer supportive evidence that NEWQOL has good validity and reliability and can discriminate between patient groups, particularly in relation to symptoms and psychological problems. We conclude that NEWQOL represents a useful measure for future studies in this patient population.     

Self-reported symptoms in patients on antiepileptic drugs in monotherapy

Wieshmann UC, Tan GM, Baker G. Self‐reported symptoms in patients on antiepileptic drugs in monotherapy.
Acta Neurol Scand: 2011: 124: 355–358.
© 2011 John Wiley & Sons A/S. Objective – To ascertain the frequency of self‐reported symptoms in patients taking antiepileptic drugs (AED). Methods – We included patients on carbamazepine (CBZ) n = 36, valproate (VPA) n = 21, levetiracetam (LEV) n = 12, phenytoin (PHT) n = 11, lamotrigine (LTG) n = 20, patients not taking anticonvulsive drugs n = 19, and healthy control subjects (CTRL) n = 41 to complete the Liverpool Adverse Event Profile (LAEP). Results – The mean LAEP scores were CBZ/PHT/LEV/VPA/LTG/noAED/CTRL = 44.97/42.00/41.00/40.33/32.42/42.00/30.80. LEV scored overall in the same range as the older AED but had a different adverse effect profile with self‐reported anger (33%) and shaky hands (42%) particularly frequent. Patients with depression or uncontrolled epilepsy had significantly higher LAEP scores than patients without depression or uncontrolled epilepsy. Conclusion – Our unblinded observational study of self‐reported symptoms suggested LTG was overall the drug with the least self‐reported symptoms. Larger studies are needed to determine whether this was a truly significant difference. LEV had a different side effect profile to older AED. Confounding factors were depression and uncontrolled epilepsy. This observation should be further tested with randomized studies.