Effect of seizures and antiepileptic drugs on prolactin secretions.

OBJECTIVE: To study the effect of seizures and antiepileptic drugs on prolactin (PRL) secretions. METHODS: Serum PRL level was measured by radioimmunoassay in 110 epileptic patients who received different treatment protocols with antiepileptic drugs (AEDs), and the test was also performed in 64 of these patients before and after seizures. Another 21 untreated epileptic patients and 42 healthy subjects served as the control groups. RESULTS: Serum PRL level was significantly increased after seizures, which peaked at 15 min postictal and attained the levels more than 5-fold the baseline in 59 patients. At 90-minute postictal, PRL levels decreased in 57 patients and dropped within normal range in 38 patients. The changes of hormone levels correlated significantly with the types of seizures. The basal PRL levels in patients with exclusive phenytion (PHT) or valproate (VPA), and in those with combined ministration of carbamazpine (CBZ+VPA+PHT), were significantly lower than the control levels (P<0.05). Patients receiving treatment with traditional Chinese medicine had comparable serum PRL levels with the normal control group (P>0.05). CONCLUSION: Seizures of epilepsy and medication with AEDs given as either monotherapy or polytherapy affect the secretion of PRL in the pituitary, but traditional Chinese medicine therapies does not.     

应用托吡酯治疗难治性癫痫的临床体会

我们选择１５例（其中７例脱落）难治性癫痫的病人,在服用基础抗癫痫药物（ＡＥＤ）的同时加用托吡酯,连续观察３个月,发现病人的发尖度均有不同程度的减少,且毒副作用极少。结合托吡酯的独特分子结构及抗癫痫机理,可以认为托吡酯是一种新型的安全有效的抗癫痫用药,尤其是对难治性部分性发作有较好的治疗效果。     

癫痫过程和抗癫痫药物治疗对泌乳素分泌的影响

目的探讨癫痫发作和抗癫痫药物治疗对泌乳素(PRL)分泌的影响。方法利用RIA法测定癫痫发作前后和应用不同抗癫痫药物治疗的癫痫患者血清中PRL水平。结果癫痫发作后PRL分泌明显升高,发作后15 min PRL分泌达到峰值,是基础PRL水平的5.1倍,发作后90 min,有89.4%的病例PRL水平下降;癫痫发作后血清PRL水平的变化与癫痫病灶位置无关;失神性癫痫发作后,血清PRL水平不升高或升高不明显,而其他类型的癫痫发作后均可引起血清PRL水平升高。苯妥英钠、丙戊酸钠单一治疗和马西平+丙戊酸钠+苯妥英钠联合治疗后,血清PRL水平降低,而纯中药治疗不影响垂体PRL的分泌。结论癫痫发作和抗癫痫药物治疗均明显影响垂体PRL的分泌。     

抗癫痫药对癫痫患者骨代谢的影响

目的 :探讨抗癫痫药对癫痫患者骨代谢影响。方法 :正常对照组 30例 ,癫痫患者组 38例 ,于抗癫痫药(患者组 )治疗前 ,治疗后 3个月、6个月分别测定血钙 (Ca)、磷 (P)、碱性磷酸酶 (ALP)、骨特异性碱性磷酸酶(BAP)、骨钙素 (BGP)、甲状旁腺素 (PTH)、2 5羟基维生素D3 [2 5 (OH)D3 ]、降钙素 (CT)等生化指标。结果 :癫痫患者治疗前和正常对照组骨代谢无显著性差异 ,癫痫患者组抗癫痫治疗 3个月、6个月后血钙、磷、碱性磷酸酶对比无明显变化 ;骨特异性碱性磷酸酶、甲状旁腺素均较治疗前增高 (P <0 .0 1 ) ;骨钙素、降钙素、2 5羟基维生素D3 均较治疗前下降 (P <0 .0 1 )。结论 :抗癫痫药可导致癫痫患者骨代谢异常 ,其中骨特异性碱性磷酸酶、甲状旁腺素、骨钙素、降钙素、2 5羟基维生素D3 可作为骨形成和骨吸收的敏感指标     

儿童期难治性癫痫的治疗进展

如何合理应用抗癫痫药物治疗儿童期难治疗癫痫以获得满意的治疗效果,已经引起广大医务工作者的广泛注意。新型抗癫痫药的问世和应用,给儿童癫痫患者的治疗带来了希望和更多的选择。虽然没有证据显示新型抗癫痫药比传统抗癫痫药更有效,但许多研究已经证明它们的抗痫谱广,药物相互作用和不良反应少,耐受性和安全性较传统抗癫痫药好。神经营养因子、抗氧化剂既有脑保护作用,又有抗癫痫作用。迷走神经刺激术、脑电刺激术、冷却法、放射疗法等物理疗法为难治性癫痫的治疗拓宽新的思路。改良后的生酮饮食疗法的临床实用性值得进一步研究。     

Refractory epilepsy: diagnosis and management

Persistence of seizures despite appropriate medical treatment is called refractory epilepsy. Persistent seizures have enormous psychosocial, behavioural and cognitive effects in addition to effects on mortality. Almost 2,40,000 to 3,20,000 patients of refractory epilepsy in India are potential candidates for epilepsy surgery. Causes of refractory or intractable epilepsy are inadequate anti-epileptic treatment, difficulty in treating some epileptic syndromes and difficulty in controlling seizures due to structural brain diseases. Careful evaluation of historical details, especially based on an eyewitness account is the most important aspect in establishing the diagnosis of epilepsy. Raised serum prolactin level helps in differentiating convulsive seizures from non-epileptic convulsions. Video electroencephalographic monitoring is proved effective and efficient mean to establish the rightful diagnosis. Recent developments in neuro-imaging have revolutionised the diagnosis of underlying pathology in patients with refractory epilepsies. Patients with refractory epilepsy should be referred to a specialised epilepsy centre where facilities for epilepsy surgery are available. When medical therapy fails, other options are helpful like use of newer anti-epileptic drugs, vagus nerve stimulation or consideration of epilepsy surgery.     

大剂量甲强龙冲击治疗小儿癫痫的临床研究

目的评价大剂量甲强龙冲击治疗小儿癫痫的疗效。方法将201例癫痫患儿随机分为治疗组（n=110）和对照组（n=91）。治疗组按癫痫分型分别给予口服传统一线抗癫痫药物,同时给予甲强龙10mg·kg-1·d-1＋0.9%氯化钠注射液100-250ml静脉滴注,静点时间〉3h以上,1次/d,连用3d,后改为口服强的松片1-2mg·kg-1·d-1,清晨6-8点空腹服用,以后按常规减量停用。对照组按癫痫分型分别给予口服传统一线抗癫痫药物,同时给予0.9%氯化钠注射液100-250ml静脉滴注作为对照,静点时间〉3h以上,1次/d,连用3d。结果治疗组总有效率为90%,明显优于对照组的65.9%,差异有统计学意义（χ2=16.024,P〈0.05）。结论甲强龙冲击治疗小儿癫痫有明显效果,且对各种发作类型均有效,不良反应少而轻,可联合抗癫痫药物应用于小儿癫痫,以及临床上一些难治性癫痫的首选治疗方案。     

Recent advances in drug therapy for epilepsy.

Recent advances in drug therapy for epilepsy have contributed to the reduction in the proportion of persons whose epilepsy is uncontrolled. New knowledge of the pharmacokinetics of phenytoin has led to a better understanding of the drug's bioavailability and uses. Carbamazepine has recently been introduced for the treatment of generalized tonic-clonic and partial seizures. Clonazepam has been found of particular benefit in the treatment of absence and myoclonic seizures. Valproic acid is a promising antiepileptic drug with broad-spectrum activity, and is particularly useful in the treatment of absence and myoclonic seizures, although further clinical experience is required before it can supplant ethosuximide as the preferred drug for the treatment of absence seizures. Monitoring of the plasma concentration of antiepileptic drugs has added greatly to the achievement of optimal drug therapy and the prevention of toxic effects.     

妥泰作为添加药治疗儿童难治性癫痫61例临床疗效分析

目的：考察妥泰作为添加药在儿童难治性癫痫治疗中的的相对疗效及安全性。方法方便选取并回顾性分析2013年7月—2015年7月该院接受检查的61例儿童难治性癫痫患者,采用自身对照法对患者进行妥泰添加治疗,治疗前12周的发作频度为基础,分别在添加妥泰治疗后8周、12周、6个月及1年对患者进行连续性观察,比较患者前后发作频度。结果患者在添加妥泰治疗后,癫痫总发作频度下降显著,发作频度下降66.09%(P<0.01);同时添加妥泰治疗后,总有效率提高明显,1年后总有效率为81.00%,差异有统计学意义(P<0.05)。结论以妥泰作为添加药对治疗儿童难治性癫痫安全有效,耐受性好,安全有效,为较好的治疗方法。     

Allopurinol as adjunctive therapy in intractable epilepsy: a double-blind and placebo-controlled trial

BACKGROUND: Adenosine has been proposed to be an endogenous anticonvulsant agent. It inhibits glutamate release from excitatory neurons and neuronal firing. Therefore, adenosine agonists have potential clinical application as antiepileptics. In this double-blind randomized, placebo-controlled trial, we assessed the antiepileptic effect of allopurinol as an adjuvant agent in 38 patients with refractory epilepsy. METHODS: Thirty eight patients were randomly allocated equally to allopurinol+preexisting antiepileptic (Group A) or placebo+preexisting antiepileptic (Group B) for a 6-month, double-blind, placebo-controlled study. The dose of allopurinol was titrated up to 300 mg/day (100 mg TDS). The dose of preexisting medications was maintained without change over the trial. The effect of allopurinol was evaluated by a reduction in the total number of seizures per month and duration of seizure attacks. RESULTS: Of 38 participants, 32 patients completed the study. There were significant differences between the two groups in terms of reduction in the total number of seizure over the trial. Seizures reduction of >30% in 66%, >50% in 55%, and >60% in 44% of cases in the allopurinol group was achieved after 2 months and persisted during the study. Nevertheless, only during month 4 was there a significant difference between the two groups regarding reduction in seizure duration. In the allopurinol group, two patients had transient rashes, two patients had mild nausea, and two experienced dizziness, but only one patient discontinued the drug due to dizziness. In the placebo group, one patient had rash and one patient had nausea. In addition, no significant hematological or hepatic changes were found during the trial in both groups. CONCLUSIONS: The results suggest allopurinol as a safe and effective adjuvant agent in refractory epilepsy. Based on this study, we suggest that purine metabolism pathways and the specific use of allopurinol should be further investigated with regards to neurobiology and treatment of refractory epilepsy.     

自发性脑出血后继发癫痫的临床研究

目的：对自发性脑出血后继发癫痫的发作特点及治疗方法进行探讨。方法：选取我院2010年1月～2015年1月收治的自发性脑出血后继发癫痫患者158例作为研究对象,对患者颅内出血部位与继发性癫痫的发作类型、发作时间之间的相关性、治疗方法等临床资料进行回顾性分析。结果：158例脑出血继发癫痫患者中脑叶出血91例,其中58例为强直阵挛发作,33例为部分性发作,非脑叶出血67例,53例为部分性发作,14例为强直阵挛发作。脑叶出血中强直阵挛发作占63.7%,非脑叶出血强直阵挛发作占20.9%,两者比较有差异。另91例脑叶出血继发癫痫患者中早发型癫痫为58例,67例非脑叶出血继发癫痫的患者中早发型仅16例,两相比较有差异。对158例脑出血继发癫痫患者,均采用常规一线抗癫痫药物治疗,排除最终12例死亡患者,133例患者均无再发癫痫,有效率达91.1%。结论：脑出血继发癫痫患者,脑叶出血多早发型,发作类型以强直阵挛发作常见,非脑叶出血多迟发型,发作类型以部分性发作常见。脑出血继发癫痫通过常规一线抗癫痫药物治疗有效。     

儿童良性癫痫伴中央颞区棘波的不典型表现

目的 探讨儿童良性癫痫伴中央颞区棘波(BECT)的不典型临床表现、脑电图特点、治疗及预后。 方法 收集2006年12月至2012年7月在齐鲁医院就诊的122例BECT患儿的临床资料,对病程中出现不典型症状的11例BECT患儿进行动态脑电图或视频脑电图监测,并对其发作时的表现、神经心理学损伤及对抗癫痫药物治疗的反应进行分析和随访。 结果 11例患儿病程中均出现发作形式的改变或脑电图恶化。2例丙戊酸钠治疗有效,4例丙戊酸钠加氯硝西泮治疗有效,3例托吡酯治疗有效。2例经多种抗癫痫药物治疗后,仍存在睡眠期脑电图癫痫性电持续状态。 结论 BECT存在不典型表现,病程中可出现不同的发作形式,同时伴有脑电图的恶化及认知行为等方面的缺陷,发作相对难以控制。     

抗氧化剂防治抗癫痫药所致周围神经损伤的实验性研究

目的探讨抗氧化剂维生素E和银杏叶提取物（Ginkgo biloba extract,GBE）对抗癫痫药物致周围神经损伤的防治功效。方法不同年龄大鼠（7d和2个月）随机分组后分别灌喂抗癫痫药物及抗氧化剂,并取坐骨神经用于组织病理观察,同时检测坐骨神经组织匀浆和大鼠血清抗氧化指标。结果补充抗氧化剂后,两年龄组原纤维病变率均显著下降（P〈0.01）,血清和周围神经组织抗氧化能力显著改善（P〈0.05,P〈0.01）。结论GBE和维生素E通过改善体内超氧化-抗氧化平衡,可有效防治抗癫痫药物导致的周围神经损伤。     

癫痫患者骨密度改变的性别差异及相关影响因素分析

目的评价癫痫患者骨密度及骨代谢相关指标的改变,探讨癫痫患者骨代谢异常的性别差异及其相关影响因素,旨在为临床治疗提供依据。方法入选110例女性癫痫患者及96例男性癫痫患者进行观察,并设立健康女性45例及健康男性40例作对照。收集癫痫患者相关临床资料,对各组分别测定骨密度及骨代谢相关生化指标,并进行统计学分析。结果癫痫组骨密度异常比例及甲状旁腺素均较健康对照组升高,女性癫痫组骨密度异常比例高于男性癫痫组（均P〈0.05）。影响因素分析中,年龄、药程、药物数量、癫痫发作对骨密度均有负面作用（均P〈0.05）,年龄对女性患者骨密度影响更加明显,病程、药物种类仅对女性患者骨密度影响显著。多因素回归分析显示,年龄、病程、药物数量是女性患者骨质异常的危险因素,而药程、药物数量是男性患者骨质异常的危险因素（均P〈0.05）。结论癫痫病及抗癫痫药（AEDs）均影响患者骨密度,并可继发甲状旁腺功能亢进。女性患者骨密度异常比例高于男性患者,且骨质异常的影响因素更多,在临床治疗中应给予更多的关注。     

加巴喷丁治疗癫痫的疗效及安全性研究

目的：加巴喷丁抗癫痫作用的有效性与安全性。方法：随机双盲，添加治疗安慰剂对照临床试验。整个试验历时6个月，入选者随机分入试验组或对照组，于试验前、入组后第1、4、8、12、16、20、24周末随访。结果：均衡性：加巴喷丁治疗癫痫在随访中均衡性较好，各指标间无明显差别。疗效评价：加巴喷丁添加治疗组结果显示较安慰剂组发作次数明显减少，两组间有统计学差别；对各类型癫痫总的治疗有效率及MMSE评分等方面无统计学差异，未显示出疗效；但对全身性强直阵挛发作类型具有明显疗效，具有统计学意义。安全性评价：加巴喷丁组和安慰剂组都有不良事件发生，加巴喷丁组居多，但差别无统计学意义。结论：加巴喷丁对全身性强直阵挛发作类型有效，对其它类型疗效不佳，是一种安全性较好的药物。     

左乙拉西坦佐治儿童难治性癫痫的疗效

目的探讨左乙拉西坦（LEV）佐治儿童难治性癫痫的临床疗效。方法选择2009年2月至2013年3月新乡医学院第三附属医院收治的难治性癫痫患儿58例,在对其行常规抗癫痫药物治疗基础上加用LEV进行佐治,并对佐治前后患儿癫痫的发作频次行Poisson回归分析。结果本组58例难治性癫痫患儿经LEV佐治,临床总有效率为74．1％（43／58）,不同类型癫痫患儿的疗效比较差异无统计学意义（P〉0．05）;行LEV佐治后综合所有类型癫痫患儿情况,其总体发作频次减少率为42．5％,癫痫发作频次佐治前后比较差异有统计学意义（P〈0．01）;本组患儿7例有轻微不良反应,均能耐受。结论LEV佐治儿童难治性癫痫临床疗效满意,且不良反应轻微,患儿治疗耐受度良好,在传统抗癫痫药物较大程度失效时可加用LEV佐治。     

影响儿童非癫痫发作性障碍诊断的因素

目的：探讨儿童非癫痫性发作（ＮＥＳ）的诊断及其影响因素。方法：根据２４ｈ动态脑电图（ＡＥＥＧ）监测,综合分析病史、体格检查、神经系统检查及影像学资料。结果：ＮＥＳ合并癫痫者占所有病例的２８％;单纯ＮＥＳ癫痫样脑波检出率为１０％;有脑器质性损害者,ＮＥＳ合并癫痫占３２％,单纯ＮＥＳ占１１％;单纯ＮＥＳ使用抗癫痫药者占１８％,合并癫痫而加用抗癫痫药者达５０％。结论：ＡＥＥＧ是鉴别ＮＥＳ与癫痫发作的较好方法;ＮＥＳ发作形式,ＮＥＳ与癫痫并存,癫痫样脑波,脑器质性损害证据及抗癫痫药滥用是影响ＮＥＳ诊断的主要因素。     

多药耐药相关蛋白1 mRNA在慢性癫痫大鼠脑中的表达

目的难治性癫痫（refractory epilepsy,RE）的发生机制尚不明确。现已明确多药耐药相关蛋白（multidrug resistance associated protein,MRP）1与某些肿瘤耐药有关。为了探讨该蛋白是否与癫痫的多药耐药相关,本研究利用大鼠癫痫模型观察癫痫发作对大鼠脑MRP1 mRNA表达的影响及左乙拉西坦（Levetiracetam,LEV）和托吡酯（Topiramate,TPM）的作用。方法通过脑立体定向技术,将海人酸（kainic acid,KA）1．5μg（3μl）注射至SD大鼠海马,制作癫痫模型。对照组大鼠海马注射3μl等渗盐水。建立模型3d后,将癫痫组和对照组大鼠各15只随机分为LEV、TPM和Ns亚组分别给予LEV（50mg／kg）、TPM（40mg／kg）和等体积NS灌胃,1次／d,共30d。用荧光定量RT—PCR测定大鼠颞叶、海马MRP1 mRNA表达水平,并进行定量分析。结果各组癫痫大鼠颞叶、海马MRP1 mRNA表达与相应非癫痫组相比呈增高趋势,但差异无统计学意义。非癫痫或癫痫大鼠各处理组间颞叶或海马MRP1 mRNA表达水平总体差异均无统计学意义。结论病程为1个月的慢性癫痫大鼠脑内MRP1 mRNA表达无明显增加,TPM、LEV不影响正常和癫痫大鼠脑MRP1 mRNA的表达。     

Vagus nerve stimulation: A novel approach for prevention and control of refractory seizures

In order to understand the brain function and to treat various neuropsychiatric illnesses including epilepsy, continued search and discovery of newer antiepileptic drugs has failed to revolutionize the approach in the management of this complex disorder. Moreover, in close to 30% of epilepsy patients, the seizure control is either not satisfactory or it is intractable to pharmacotherapy. Amongst the non-pharmacological treatment options for refractory epilepsy, vagus nerve stimulation occupies a unique position as an adjunctive treatment in prevention and control of partial-onset seizures in adults and adolescents older than 12 years. Though the precise mode of action of VNS is still debatable an honest attempt has been mode here to review all possible literatures available on VNS to establish its role in the management of this complex disorder. Key words: Neuropsychiatric illness, Intractable Epilepsy, Vagus nerve stimulation, Seizure control.