Docosahexaenoic acid prevents resistance to antiepileptic drugs in two animal models of drug-resistant epilepsy

Objectives: One-third of epileptic patients are resistant to antiepileptic drugs. Few clinical studies with small sample size indicate that polyunsaturated fatty acids could control drug-resistant epilepsy. We examined the efficacy of acute and chronic administration of docosahexaenoic acid (DHA) in two animal models of drug-resistant epilepsies, i.e. 6-Hz psychomotor seizures in mice and lamotrigine (LTG)-resistant kindled rats.

Methods: Mice received a single injection of DHA (300?µM, i.c.v.) along with phenytoin (PHT) or LTG (i.p.). Six-Hz electroshock (0.2?milliseconds rectangular pulse width, 3?seconds duration, 44?mA current) was given 15 minutes after DHA, and seizure behaviors were recorded. In LTG-resistant kindled rats, a single dose of DHA (300?µM, i.c.v.) was administered with LTG, and seizure parameters were measured. In chronic treatment, mice received DHA (0.1?g/day, orally) for 30 days. Then, a single dose of LTG or PHT was administered to mice and 6-Hz-induced seizures were recorded. In rats, DHA (1?µM, i.c.v.) was administered during kindling development and effect of LTG in DHA-pretreated LTG-resistant kindled rats was verified.

Results: LTG and PHT did not inhibit 6-Hz seizures in mice after single injection of DHA. However, LTG and PHT inhibited 6-Hz seizures in mice that received DHA for 1?month. Acute or chronic administration of DHA to LTG-resistant kindled rats led to the suppression of kindled seizure parameters by LTG.

Discussion: DHA removes the ‘inherent resistance’ of 6-Hz seizures to PHT and LTG, and prevents the development of pharmacodynamic tolerance to LTG in LTG-resistant kindled rats. DHA might have potential to be used as add-on therapy in patients with refractory epilepsy.     

Health and Safety Issues Relating to Maine's Fishing Industry

SUMMARY

The Maine Agricultural Safety and Health Program performed a needs assessment to determine the health and safety concerns of Maine's fishing community. Information for the assessment was obtained from clinicians, focus groups of wives of fishers, and government agencies. Reports from the United States Coast Guard showed that during 1993-1994, sixty-five people were injured on commercial fishing vessels and eight people died. Decompression illness was the most frequently reported non-fatal injury (n = 15). Chronic injuries reported by clinicians included back pain, tendinitis, carpal tunnel syndrome, dysbaric osteonecrosis. Clinicians and family members were also concerned about hand and arm infections from the bait and sun exposure. Family health issues and access to care are addressed in the report. Recommendations include, in part, increasing surveillance, reducing barriers to access, increasing clini-cians' knowledge about the fishing industry, and fostering collabora-tion between agencies providing health and safety information to fishers.     

Looking ahead: planning for the first human intracortical visual prosthesis by using pilot data from focus groups of potential users

In planning for our research team's first human implant of a technologically advanced intracortical visual prosthesis we have conducted three focus groups with blind persons from a pool of likely participants. Guided by the principles of the Independent Living movement and Participatory Action Research (PAR), we asked the participants to share their thoughts and concerns about the procedure. The preliminary results reveal that achievement of the desired highest ethical of informed consent will require extensive pre-operative learning opportunities, such as those provided by these focus groups. Persons who are blind may be motivated to participate in research like this based on a need to know, understand, and explore ones environment, to leave a legacy, and to experience some restored perception.     

灵芝多糖对癫痫大鼠脑中谷氨酸转运体的影响

目的：观察和探讨灵芝多糖干预后戊四氮（ PTZ）致痫大鼠皮质和海马区兴奋性谷氨酸转运体（EAAT）GLAST（EAAT1）、GLT1（EAAT2）、EAAC1（EAAT3）的变化,进一步研究癫痫的发病机制及灵芝多糖的作用机制。方法 SD 大鼠32只,随机分为正常对照组、癫痫模型组、灵芝多糖组和卡马西平组,每组8只。癫痫组、灵芝多糖组和卡马西平组采用 PTZ 腹腔注射制作慢性癫痫点燃模型。实验结束后断头迅速取脑,采用免疫组化法检测皮质和海马区各指标的变化。结果癫痫模型组大鼠脑中 GLAST、GLT1、EAAC1的表达较正常对照组降低：皮质（31.87±4.76）、（48.00±5.34）,（42.87±4.01）、（52.12±3.75）,（40.25±2.81）、（46.87±3.04）;海马：（29.87±4.32）、（44.51±4.81）,（36.50±3.02）、（47.00±3.20）,（35.62±3.42）、（42.12±3.56）;灵芝多糖和卡马西平组大鼠脑中 GLAST1、GLT1、EAAC1的表达较癫痫模型组升高：皮质（40.50±4.47）、（31.87±4.76）,（48.87±3.48）、（42.87±4.01）,（43.87±2.53）、（40.25±2.81）;海马：（37.75±3.61）、（29.87±4.32）,（41.25±2.60）、（36.50±3.02）,（39.50±2.61）、（35.62±3.42）。灵芝多糖组和卡马西平组之间 GLAST1、GLT1、EAAC1三者的表达无统计学意义。结论灵芝多糖能够升高癫痫大鼠脑中 GLAST、GLT1、EAAC1的表达,加速了兴奋性氨基酸 Glu（谷氨酸）的清除。降低神经元兴奋性、减少神经系统损伤而抑制癫痫的发作。     

皮层脑电图监测下癫痫病人手术治疗的麻醉处理

目的:探讨皮层脑电图(ECoG)监测下癫痫病人手术治疗的麻醉方案及管理方法.方法:选择40例需行手术治疗的癫痫病人作为研究对象,随机分为静吸复合麻醉组(A组)和全静脉麻醉组(B组).A组采用七氟烷静吸复合麻醉,B组采用丙泊酚靶控静脉麻醉,观察2组七氟烷吸入浓度及丙泊酚靶浓度分别为1.5最低肺泡有效浓度(MAC)或5.0μg/mL(T1)、1.0 MAC或3.0μg/ML(T2)、0.5 MAC或1.5μg/mL(T3)时ECoG出现爆发性抑制波例数、术中棘波频率变化以及血流动力学变化情况.结果:在T2、T3时刻,2组癫痫手术过程中ECoG可准确描记癫痫波且血流动力学指标稳定.2组病人在T1时刻ECoG出现爆发抑制波的例数最多,随着麻醉药物浓度的降低,2组ECoG监测到的爆发抑制波出现次数逐渐减少.但在不同时刻,2组在血流动力学指标、爆发抑制波和棘波出现情况差异均无统计学意义(P>0.05).结论:七氟烷与丙泊酚对癫痫病人ECoG的影响均呈剂量依赖型,但在一定麻醉深度下不影响ECoG对癫痫波的识别及病灶定位,可安全用于癫痫病灶切除手术麻醉.     

依托咪酯语言及记忆评估的Wada试验在癫痫外科运动、语言和记忆评估中的初步应用

目的 依托咪酯语言及记忆评估的Wada试验(etomidate speech and memory-Wada testing, eSAM-Wada)在我国还未见相关报道,而血管超选下eSAM-Wada试验国内外还未见报道。探讨eSAM-Wada试验的安全性及其对运动、语言和记忆功能评估的效果。 方法 本文通过回顾性分析我中心5例行eSAM-Wada试验的难治性癫痫患者,观察操作过程中患者运动、语言及记忆功能的改变和术中的不良反应。结果：5例患者均可完成整个评估流程,智商偏低的患者仍可配合完成。2例患者完成血管超选下的eSAM-Wada试验。3例左利手患者中,2例(66.7%)语言优势侧仍位于左侧半球,2例(100%)右利手患者语言优势侧均位于左侧半球。4例左侧半球病变的患者,2例(50%)记忆的优势侧仍位于左侧颞叶,1例(25%)记忆为双侧优势,1例(25%)记忆优势侧转移至右侧颞叶。2例患者进行了后续切除性手术,1例患者进行了立体定向脑电图电极引导下热凝毁损术,1例患者出现左下肢一过性无力,运动、语言及记忆功能改变均与eSAM-Wada试验预测结果相符。2例患者(40%)出现癫痫发作可能与操作流程中依托咪酯静脉推注给药速度过快有关,后给药速度改为>30秒后,患者再无癫痫发作。不良反应需要进一步观察。结论：eSAM-Wada试验是全面评估运动、语言及记忆评估较为可靠且相对安全的方法。与血管超选技术结合,可以更加有效的指导涉及功能区的颅脑外科手术治疗。由于病例数量有限,结论尚需进一步观察。     

Use of levetiracetam in treating epilepsy associated with other medical conditions

OBJECTIVE: This prospective, open-label study was conducted to evaluate the effectiveness, tolerability, and safety of levetiracetam in patients with epilepsy in whom unfavorable metabolism, complex drug interactions, or direct toxic effects of antiepileptic drugs (AEDs) had caused a worsening of comorbid conditions. METHODS: Study design included the introduction of levetiracetam, discontinuation of other AEDs, and a serial assessment comprising electroencephalograms and blood tests at baseline and 2, 6, and 12 months. Of 21 patients, 16 had partial and five generalized epilepsy. Concomitant pathologies were gastroenterological (six), vascular (four), endocrinological (four), or complex conditions including hematological (four) or dermatological (three) disease. A change of regimen was necessitated by drug-drug interactions in four patients, direct real or potential toxic effects of previous AEDs in 13, and a combination of interactions/toxic effects in four. RESULTS: After 12 months, 12 patients were seizure-free, nine had reductions in seizure frequency of 50-75%, and improvement in concomitant medical conditions was observed. No side effects were reported. CONCLUSION: Levetiracetam appears to be effective, well tolerated, and safe in patients with epilepsy and other medical conditions that are difficult to manage because of drug interactions or AED-related side effects.     

Clinical relevance of memory performance during Wada is stimulus type dependent

OBJECTIVES: This study aimed to investigate whether different types of memory stimulus provide different information during the Wada or intracarotid amytal procedure (IAP) in patients with refractory medial temporal lobe epilepsy (MTLE). METHODS: Eighty nine surgical candidates with documented MTLE and selected for left hemispheric language dominance underwent memory assessment with verbal and dually encodable stimuli during a presurgical IAP. RESULTS: The overall IAP memory performance with the left hemisphere is significantly better than with the right hemisphere regardless of lesion side. This can be explained by the left hemispheric advantage of encoding all stimuli, whereas the right hemisphere has only limited resources to encode verbal stimuli. More importantly, it appeared that dually encodable items remain more readily recognised following injection ipsilateral to the lesion, whereas verbal items are always better recognised following right hemisphere injection regardless of lesion side. CONCLUSIONS: Verbal IAP stimuli show left hemispheric sensitivity in left language dominant MTLE patients. The dually encodable items of the IAP appear lesion sensitive.     

顽固性颞叶癫(癎)海马超微结构的体视学分析

目的对顽固性颞叶癫痫病人的海马癫痫灶组织和癫痫灶周围正常组织的超微结构进行形态定量观察，以探讨颞叶癫痫的发生机制．方法对45例病人在深部电极监测下手术切除海马．电镜观察癫痫灶组织和癫痫灶周围正常组织中锥体细胞和突触结构的形态学变化：采用体视学分析颞叶癫痫灶组织和癫痫灶周围正常组织锥体细胞线粒体体积密度（Vv）、面积密度（Sv）、数密度（Nv）、比表面积（δ）、平均体积（V）：测量突触间隙的宽度。结果癫痫灶组织锥体细胞线粒体较癫痫灶周围正常组织明显肿胀，且嵴断裂．数量减少，平均截面积增大：线粒体的Vv、V较癫痫灶周围正常组织大，Sv、Nv、8较癫痫灶周围正常组织小。癫痫灶组织中锥体细胞的轴突和树突内线粒体较癫痫灶周围正常组织的锥体细胞肿胀明显；轴棘、轴树突触间隙宽度变窄。结论海马锥体细胞超微结构的改变和细胞线粒体功能变化与顽固性颞叶癫痫的发生关系密切。     

托吡酯对戊四氮点燃慢性癫(癎)大鼠海马神经细胞黏附分子的影响

目的:探讨神经元活化在癫发生、发展中的作用及托吡酯对其的影响。方法:采用戊四氮制备慢性癫模型,利用托吡酯干扰,选取不同时间点,观察大鼠行为学变化及神经细胞黏附分子在海马回的表达(免疫组织化学染色)。结果:托吡酯组点燃率在27d明显低于模型组;模型组及托吡酯组神经细胞黏附分子表达增加,并随时间延长明显;而不同时间点该表达的增加程度,托吡酯组均低于模型组。结论:神经细胞黏附分子表达的增加,说明出现了神经元活化及脑可塑性变化,而托吡酯明显地抑制了该表达的增加。