Domoic Acid Epileptic Disease

Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis.     

Suspected Limbic Encephalitis and Seizure in Cats Associated with Voltage‐Gated Potassium Channel (VGKC) Complex Antibody

Background

Treatment‐resistant complex partial seizures (CPS) with orofacial involvement recently were reported in cats in association with hippocampal pathology. The features had some similarity to those described in humans with limbic encephalitis and voltage‐gated potassium channel (VGKC) complex antibody.

Hypothesis/Objectives

The purpose of this pilot study was to evaluate cats with CPS and orofacial involvement for the presence of VGKC‐complex antibody.

Animals

Client‐owned cats with acute orofacial CPS and control cats were investigated.

Methods

Prospective study. Serum was collected from 14 cats in the acute stage of the disease and compared with 19 controls. VGKC‐complex antibodies were determined by routine immunoprecipitation and by binding to leucine‐rich glioma inactivated 1 (LGI1) and contactin‐associated protein‐like 2 (CASPR2), the 2 main targets of VGKC‐complex antibodies in humans.

Results

Five of the 14 affected cats, but none of the 19 controls, had VGKC‐complex antibody concentrations above the cut‐off concentration (>100 pmol/L) based on control samples and similar to those found in humans. Antibodies in 4 cats were directed against LGI1, and none were directed against CASPR2. Follow‐up sera were available for 5 cats in remission and all antibody concentrations were within the reference range.

Conclusion and Clinical Importance

Our study suggests that an autoimmune limbic encephalitis exists in cats and that VGKC‐complex/LGI1 antibodies may play a role in this disorder, as they are thought to in humans.     

癫痫患者血浆皮质醇浓度测定的临床意义

本文对47例癫痫患者血浆皮质醇浓度作了测定,结果表明:癫痫发作期及间歇期的血浆皮质醇浓度高于对照组(P<0.01,0.05),发作期又高于间歇期(P<0.01);原发性癫痫控制期与对照组浓度比较无差异(P>0.05);继发性癫痫发作期、间歇期浓度分别高于原发性癫痫发作期、间歇期(P<0.01);苯妥英钠治疗与丙戊酸钠治疗组浓度比较元差异(P>0.05),但后者高于对照组(P<0.05)。对其机理和临床意义作了探讨。     

Magnetic resonance imaging findings in Finnish Spitz dogs with focal epilepsy

Eleven Finnish Spitz dogs with focal seizures and 3 healthy controls were evaluated. General clinical and neurological examinations, blood examination, urinalysis, cerebrospinal fluid examination, electroencephalography (EEG), and magnetic resonance imaging (MRI) of the brain were performed on all dogs. On EEG examination, focal epileptic activity was found in 7 of 11 dogs (64%), and generalized epileptic activity was observed in 4 of 11 dogs (36%). MRI (performed with 1.5 T equipment) detected changes in 1 epileptic dog. Mild contrast enhancement after gadolinium injection was identified in this dog's right parietal cortex. However, no such changes were observed in repeated magnetic resonance images. Special emphasis was given to seizure history to determine any correlations between seizure intervals and MRI findings. Our results indicate that Finnish Spitz dogs with focal seizures suffer from focal idiopathic epilepsy and have nondetectable findings on MRI or pathology. MRI showed poor sensitivity in detecting epileptogenic areas in our patients with focal seizures. Reversible MRI changes in 1 dog could have been caused by seizures.     

癫痫小鼠颅脑损伤后海马与顶叶皮质中C-FOS蛋白的表达

【目的】探讨具有癫痫基础病变小鼠在遭受颅脑损伤时,海马和顶叶皮质中CFOS表达与损伤的相关性及其在损伤中的意义,为癫痫后颅脑损伤复合病变研究提供理论依据。【方法】用腹腔注射匹罗卡品法构建小鼠（2周龄）癫痫模型,饲养4周后（6周龄）采用自由落体法构建闭合性颅脑损伤小鼠模型和癫痫+闭合性颅脑损伤小鼠模型,同时以正常小鼠为对照,于造模后0.5,3 h及1,3,7 d取小鼠大脑,制备切片,采用尼氏染色、免疫组织化学染色方法,从形态学以及蛋白质水平上研究各组小鼠大脑海马和顶叶皮质中C-FOS的表达情况。【结果】癫痫模型、闭合性颅脑损伤模型及癫痫+闭合性颅脑损伤小鼠模型均构建成功。免疫组织化学染色结果显示,癫痫合并闭合性颅脑损伤小鼠顶叶皮质、海马均有着色深浅不同、数目不等的C-FOS阳性细胞。与对照组相比,单纯癫痫组、单纯闭合性颅脑损伤组、癫痫+闭合性颅脑损伤组C-FOS灰度值均显著（P<0.05）或极显著降低(P<0.01);癫痫+闭合性颅脑损伤组小鼠海马和顶叶皮质C-FOS阳性细胞数均显著（P<0.05）或极显著（P<0.01）高于单纯癫痫组与单纯闭合性颅脑损伤组。【结论】癫痫小鼠颅脑损伤后,海马和顶叶皮质持续高表达C-FOS,从而促进神经细胞凋亡,加重颅脑损伤后的病理变化。     

愈痫灵方对难治性癫痫大鼠多药耐药相关蛋白MRP1、P-gp、LAP、MCP-1表达的作用

目的 探讨“愈痫灵”方对红藻氨酸（KA）致痫难治性癫痫模型大鼠海马及颞叶皮质区多药耐药相关蛋白1（MRP₁）、P糖蛋白（P-gp）、层黏连蛋白（LAP）以及单核细胞趋化蛋白1（MCP-1）表达的影响。方法 （1）造模：在脑立体定位仪引导下,海马区微量进样器注入KA1.0μL（即1.0μg）点燃发作,选取发作行为级别在Racines标准Ⅳ级以上者,以丙戊酸钠及卡马西平灌胃干预14 d后,再次以亚惊厥剂量KA0.5μL复燃,筛选再次发作级别在Ⅳ级以上或持续状态大鼠,且脑电图检测有癫痫样波放电者为造模成功的耐药难治性癫痫模型鼠。（2）分组与处理：造模成功鼠随机分为愈痫灵方干预组、拉莫三嗪对照组、模型组,另设假手术对照组、空白对照组共5组,分别给予“愈痫灵”汤剂、拉莫三嗪及同等体积的蒸馏水（2 mL/d）灌胃30 d。（3）标本处置与检测：采用免疫组织化学技术,检测多药耐药相关蛋白MRP₁、P-gp、LAP、MCP-1在海马与颞叶皮层的表达。结果 与假手术对照组、空白对照组间比较,造模成功组海马区及颞叶皮质区MRP₁、P-gp、LAP、MCP-1的表达均明显升高,差异有统计学意义（P<0.01）;与模型组比较,愈痫灵、拉莫三嗪干预处理后能显著降低模型鼠海马区MRP₁、P-gp表达水平（P<0.05）,海马区及颞叶皮质区LAP、MCP-1的表达差异均无统计学意义（P>0.05）;愈痫灵方组与拉莫三嗪组比较,差异均无统计学意义（P>0.05）;各组间颞叶皮质区LAP、MCP-1表达差异无统计学意义（P>0.05）。结论 耐药性癫痫大鼠模型海马及颞叶皮质区多药耐药相关蛋白MRP₁、P-gp、LAP、MCP-1表达均明显升高,逆转与降低海马区MRP₁、P-gp的表达可能是“愈痫灵”方抗耐药性癫痫作用机制之一。     

穴位埋药线对难治性癫痫大鼠癫痫样波的发放及大脑海马和颞叶皮质多药耐药相关蛋白MRP1、P-gp表达的影响

目的 探讨穴位埋药线对难治性癫痫大鼠癫痫样波的发放及大脑海马和皮质中多药耐药相关蛋白MRP₁、P-gp表达的影响。方法 （1）造模：大鼠海马区注射红藻氨酸（KA）,经过点燃和再次亚惊厥剂量点燃造模,且脑电图检测有癫痫样波发放者筛选为造模成功耐药难治性癫痫模型鼠。（2）分组与处理：普通线组（PTX组）与药线组（YX组）,先埋一侧穴位,间隔15 d后埋对侧穴位。拉莫三嗪组（LTG组）按照人用拉莫三嗪剂量换算灌胃大鼠,每日2次;空白对照组（Normal组）和模型组（Model组）给予灌胃同等体积的蒸馏水,均灌胃30 d。（3）采用VEEG-1518K型数字化视频脑电监测分析系统检测脑波基本节律的波幅与频率变化。（4）标本处理与检测：采用免疫组织化学技术,检测多药耐药相关蛋白MRP₁、P-gp在海马与颞叶皮层不同部位的表达。结果 各组治疗前比较差异无统计学意义（P>0.05）;各组治疗后,YX组、LTG组分别与Model组、PTX组比较差异有统计学意义（P<0.05）,YX组与LTG组比较差异无统计学意义（P>0.05）;与Model组相比,LTG组和YX组干预后能降低致痫鼠EEG痫波放电持续时间与发放频率以及海马区和颞叶皮质区多药耐药蛋白MRP₁、P-gp的表达水平（P<0.05或P<0.01）;YX组与PTG组比较差异无统计学意义（P<0.05）。结论 （1）埋药线使KA致痫鼠EEG痫波放电持续时间缩短,发放频率减少。（2）KA点燃难治性癫痫模型大鼠大脑海马区存在多药耐药蛋白MRP₁、P-gp的表达较皮质区明显升高。（3）埋药线逆转与降低致痫鼠海马区多药耐药蛋白MRP₁、P-gp的表达水平,可能是其抗癫痫生物学作用机制之一。     

国医大师熊继柏从痰辨治神志病医案举隅

国医大师熊继柏认为神志病主要责之于心,痰饮是导致神志病的重要病理因素,化痰法是中医治疗神志病的常用方法,但必须以神志异常,兼痰多、苔腻、脉滑为辨证要点。通过列举癫证、狂证、痫证、失眠、梅核气5个医案,介绍熊教授从痰辨治神志病的经验与方法。