脑静脉窦血栓形成的治疗进展

脑静脉窦血栓形成(cerebral venous and sinus thrombosis, CVST)是由多种病因所致的以脑静脉回流障碍伴颅内压增高为特征的特殊类型脑血管病,占全部脑血管病的0．5%~1%。 CVST的早期诊断和治疗对患者的预后有着显著的影响。文章对 CVST 的治疗进展进行了综述。     

Evaluation of fosphenytoin,levetiracetam, and propofol as treatments for nerve agent-induced seizures in pediatric and adult rats

Multiple recent instances of nerve agent (NA) exposure in civilian populations have occurred, resulting in a variety of negative effects and lethality in both adult and pediatric populations. Seizures are a prominent effect of NAs that can result in neurological damage and contribute to their lethality. Current anticonvulsant treatments for NAs are approved for adults, but no approved pediatric treatments exist. Further, the vast majority of NA-related research in animals has been conducted in adult male subjects. There is a need for research that includes female and pediatric populations in testing. In this project, adult and pediatric male and female rats were challenged with sarin or VX and then treated with fosphenytoin, levetiracetam, or propofol. In this study, fosphenytoin and levetiracetam failed to terminate seizure activity when animals were treated 5 min after seizure onset. Propofol was effective, exhibiting high efficacy and potency for terminating seizure activity quickly in pediatric and adult animals, suggesting it may be an effective anticonvulsant for NA-induced seizures in pediatric populations.     

Valproate in the treatment of epilepsy in girls and women of childbearing potential

This document provides guidance on the use of valproate in girls and women of childbearing age from a joint Task Force of the Commission on European Affairs of the International League Against Epilepsy (CEA‐ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures‐Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in infants who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use of valproate and treatment alternatives, the importance of seizure control and of patient and fetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Force's recommendations include the following: (1) Where possible, valproate should be avoided in women of childbearing potential. (2) The choice of treatment for girls and women of childbearing potential should be based on a shared decision between clinician and patient, and where appropriate, the patient's representatives. Discussions should include a careful risk–benefit assessment of reasonable treatment options for the patient's seizure or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most effective treatment, the risks and benefits of valproate and other treatment alternatives should be discussed. (4) Valproate should not be prescribed as a first‐line treatment for focal epilepsy. (5) Valproate may be offered as a first‐line treatment for epilepsy syndromes where it is the most effective treatment, including idiopathic (genetic) generalized syndromes associated with tonic–clonic seizures. (6) Valproate may be offered as a first‐line treatment in situations where pregnancy is highly unlikely (e.g., significant intellectual or physical disability). (7) Women and girls taking valproate require regular follow‐up for ongoing consideration of the most appropriate treatment regimen.     

The antiepileptic primidone impairs male rat sexual behavior

Many antiepileptic drugs (AEDs) produce sexual impairments. Of commonly prescribed AEDs, primidone produces the greatest impairments. Here we examined the effects of primidone on male rat sexual behavior. Sexually-experienced male rats received administration of either vehicle or primidone. After baseline measures were obtained, the effects of daily primidone treatment on home cage sexual performance were assessed three times over the course of 14 days. Motor activity and sucrose preference were also assessed during this time period. Results indicate that primidone impaired copulation but not sexual motivation. Specifically, animals receiving primidone displayed fewer ejaculations, required more time to achieve an intromission, and displayed fewer intromissions per attempted mount as evidenced by a lower intromission ratio. However, animals treated with primidone also chose a goal box containing a sexually-receptive female in an x-maze as often as animals receiving vehicle. The lower intromission ratio suggests an inability to achieve intromissions perhaps as a result of impaired erectile function. Primidone did not affect motor activity or sucrose consumption, an additional measure of natural reward. Together, these data indicate that primidone impairs male sexual activity and suggest that these impairments result primarily from changes in erectile function and not changes to mechanisms mediating motivation.     

Extended‐release antiepileptic drugs: A comparison of pharmacokinetic parameters relative to original immediate‐release formulations

Many antiepileptic drugs (AEDs) have short half‐lives with large fluctuations in peak‐to‐trough plasma concentrations. Consequences of these pharmacokinetic (PK) properties may include adverse events (AEs) and breakthrough seizures, potentially leading to poor adherence. To address these challenges, newer formulations of these AEDs have been developed using unique extended‐release (ER) technologies. These technologies extend the dosing interval such that dosing frequency can be minimized, which may improve patient adherence. Available ER formulations have the potential to minimize the spikes in maximum plasma concentrations (C_max) at steady‐state that often contribute to AEs during treatment with immediate‐release (IR) products. In so doing, tolerability advantages may lead to increased AED effectiveness by improving adherence and allowing higher doses if clinically indicated. Direct PK comparison studies of IR and ER formulations (e.g., carbamazepine, divalproate sodium, lamotrigine, oxcarbazepine, levetiracetam, and phenytoin) have found that dose‐normalized ER formulations may or may not be bioequivalent to their IR counterparts, but most ER formulations have a lower fluctuation index ([C_max–C_min]/C_avg) compared with the IR versions. This results in flatter concentration‐time plots. Not all ER preparations improve the various PK parameters to the same extent, and PK nuances may impact the effectiveness, tolerability, and adherence rates of various ER formulations.     

Lamotrigine in mood disorders

SUMMARY

Lamotrigine is an anticonvulsant drug with good efficacy and safety in the treatment of epilepsy. There is now substantial evidence that lamotrigine is also useful in treating resistant depression, rapid cycling bipolar affective disorder, depressive episodes in bipolar affective disorder and in the maintenance phase or prophylaxis of bipolar affective disorder. There are possible roles in managing mood changes in borderline personality disorder, reducing chronic pain and treating schizoaffective disorder.

The general range of doses found effective in affective disorders is from 50 to 300?mg daily.

Clinical use seems to involve a titration of dose upwards over several weeks until the desired ! effect is obtained.

However, further definitive double-blind, randomised controlled trials against gold standard treatments are required.

Lamotrigine has a preferable side-effect profile compared to standard agents for bipolar affective disorder such as lithium or carbamazepine. Further research is certainly warranted and, given its tolerability, could point to lamotrigine as the treatment of choice for some affective disorders.     

拉莫三嗪对部分性发作癫痫患者认知功能及生活质量的影响

目的 评价拉莫三嗪(LTG)对部分性发作癫痫患者认知功能以及生活质量的影响.方法 对26例新诊断的部分性发作的癫痫患者随机分为两组,LTG组14例,给予LTG治疗,卡马西平(CBZ)组12例,给予CBZ治疗,在用药前及用药后16周进行认知功能评定及生活质量调查.认知功能评定包括数字广度,词语流畅、连线测验(A、B型)、Stroop字色干扰测验、威斯康星卡片分类测验(WCST)、延迟逻辑记忆、延迟视觉记忆、计算力、数字符号转换测验;生活质量调查采用癫痫患者生活质量评定量表-31(QOLIE-31). 结果癫痫患者应用LTG治疗16周后认知功能与用药前比较词语流畅性增加,A型、B型连线测验时间缩短,WCST正确数、分类数增加,持续错误、操作时间减少,数字符号转换测验增加,延迟逻辑记忆增加,延迟视觉记忆增加,均有统计学意义(t=3.043、-3.287、-2.543、3.167、3.028、-2.191、-3.216、3.061、3.036、3.021,P<0.01或P<0.05).两组治疗前后差值比较,LTG组比CBZ组Stroop读色时间减少,数字符号转换测验增加,计算力增加,差异均有统计学意义(t=3.167、2.142、2.101,P<0.01或P<0.05).QOLIE-31调查结果显示,与治疗前比较,LTG组和CBZ组治疗后综合生活质量、总体健康水平、认知功能、社会功能得分均增加(LTG组:t=3.321、2.462、3.294、3.512;CBZ组:t=3.314、3.149、3.294、3.202;P<0.01或P<0.05);LTG组与CBZ组治疗前后差值比较,认知功能、社会功能明显改善(t=2.257、2.140,均P<0.05),对发作的担心也减少(t=2.147、P<0.05). 结论 拉莫三嗪能够改善新诊断的部分性发作的癫痫患者认知功能,并提高生活质量.     

单药治疗的癫患儿认知功能的

目的了解影响癫患儿认知功能的因素,尤其是抗癫药物(苯巴比妥、卡马西平、丙戊酸)对其有无影响.方法对38例单药治疗的癫患儿及15例正常儿童的多项认知功能指标进行6～12个月的随访研究.结果(1)癫患儿言语智商(106±11)、短时视觉记忆(12.3±4.2)及对外界信息的反应速度[单音辨认反应时间(492±75)ms、汉字辨认反应时间(615±99)ms]均落后于正常同龄儿[分别为112±7、14.9±3.8、(443±55)ms、(558±70)ms,P均<0.05].(2)癫患儿的认知功能水平是多因素共同作用的结果①年龄是影响癫患儿及正常儿多项认知指标的共同因素;②抗癫药种类与短时视觉记忆、言语智商及注意力指标有关;血药浓度和服药时间与各认知指标无关;③患病时间、临床发作类型、发作持续时间、惊厥持续状态史等因素对短时视觉记忆、注意力、反应速度及手的协调运动等方面产生影响,不同因素作用的方面有所不同.(3)单药治疗已控制发作的癫患儿,多数认知指标发育与同龄儿持平,仅汉字结构辨认事件相关电位P3潜伏期的缩短速度落后于同龄儿[前后2次测验差值癫组为(5.17±30.95)ms,对照组为(-13.04±1.91)ms,P＜0.05].结论癫患儿的认知功能状态及发育受多因素共同影响,抗癫药物仅为其因素之一,药物治疗效果良好并已控制发作的患儿多项认知功能发育水平与同龄儿持平.