神经皮肤黑变病合并部分性癫

目的讨论神经皮肤黑变病(NCM)合并部分性癫的手术治疗及效果。方法回顾性分析1例NCM合并癫病人的临床资料。皮质电极监测后,行颞极及颞叶新皮质部分切除术。结果术后脑组织病理提示:颞极见大量黑色素细胞,原发性脑膜黑色素细胞增生症。皮肤病理提示复合性色素痣。术后10个月无癫发作。Engel分级Ⅰ级。结论 NCM是癫的罕见原因,但手术治疗效果满意。致灶切除术是一种安全有效的治疗方法。     

皮质电刺激在功能区致疒间灶手术中的应用

目的：分析皮质电刺激在功能区致疒间灶手术中的应用。方法回顾性分析8例功能区难治性癫疒间病人的临床资料。根据视频脑电图及电刺激结果，确定致疒间灶与功能区之间位置关系，术中保护功能区，最大程度切除致疒间灶。结果手术顺利，术后2例左额叶软化灶病人术前肌力4级，术后无肌力下降；1例右枕叶皮质发育不良病人，术后视野部分缺损。随访6个月~3年，6例病人无癫疒间发作，2例病人发作减少90%。Engel分级Ⅰ~Ⅱ级。结论皮质电刺激是定位大脑功能区的金标准，应用皮质电刺激治疗功能区癫疒间可以在保留功能区的基础上最大程度切除致疒间区，提高癫疒间病人生活质量，更好地控制癫疒间。     

皮层脑电监测下颞叶病变合并癫的手术治疗

目的探讨皮层脑电监测下合并颞叶病变的癫手术治疗效果。方法 21例伴有癫症状的颞叶病变患者,术中通过皮层脑电图确定癫灶,切除病变后,切除或热灼可疑癫疒间灶。术后随访患者的癫发作情况。结果 21例患者切除颞叶病变前均可通过皮层脑电图探及疒间波,病变及疒间灶完全切除后,癫波消失者19例,2例功能区患者虽多次皮层热灼,仍可见偶发棘波。术后20例未再有癫疒间发作,1例有部分性发作,用抗癫疒间药可控制。结论术中皮层脑电监测切除或热灼癫灶是一种有效控制颞叶病变切除术后癫发作的方法。     

多种术式联合治疗难治性额叶癫疒间临床分析

目的观察额叶致疒间灶切除术和选择性胼胝体切开术联合癫疒间灶周围多处软膜下横纤维切断手术治疗难治性额叶癫疒间的临床疗效。方法分析在我院接受多种术式联合治疗的19例难治性额叶癫疒间的临床资料,应用Engel标准进行术后效果分级,并对其中15例随访6个月~4a,总结手术体会,评价其远期疗效。结果按Engel分级:Ⅰ~Ⅱ级15例(78.9%),Ⅲ级4例(21.1%)。术后出现短暂肢体偏瘫6例,缄默2例,小便失禁3例,无死亡。癫疒间灶病理检查多为神经元变性及胶质增生。结论难治性额叶癫疒间手术治疗效果较满意,需要多种术式联合治疗才能提高手术效果。     

颅内视通路多发节细胞胶质瘤癫疒间的手术治疗

目的总结颅内视通路多发节细胞胶质瘤癫疒间的诊治经验。方法回顾性分析2例以癫疒间发作为首发症状的颅内视通路多发节细胞胶质瘤病例资料。MRI均显示左侧视通路(视交叉、视束、外侧膝状体)多发性病灶。术前评估为左侧颞叶癫疒间,均在术中唤醒下实施裁剪式左侧前颞叶(含杏仁核、海马)切除,同时切除部分视通路病变,其中1例术中部分切除视交叉病变。结果术后病人视野缺损均不同程度加重。术后病理报告为颞叶局灶性皮质发育不良,海马硬化,节细胞胶质瘤。术后癫疒间控制分别达到Engel分级Ⅱa级和Ⅰa级。结论节细胞胶质瘤属良性神经元胶质细胞混合性肿瘤(WHOⅠ级),最常见症状为癫疒间发作。视通路节细胞胶质瘤极罕见,颞叶癫疒间+视通路多发病灶是特征性临床表现。手术治疗应以控制癫疒间发作为主要目的,无需过多切除非致疒间性的肿瘤灶而加重视觉功能缺失。     

颅内电极置入与脑功能区定位技术在功能区难治性癫疒间手术的应用

目的探讨颅内电极埋藏与脑功能区定位技术在功能区起始的难治性癫疒间手术的评估价值。方法回顾性分析7例难治性癫疒间的临床资料,头皮视频脑电图长程监测均考虑致疒间灶可能累及功能区,故行颅内电极置入术,再行皮质电极视频脑电图长程监测,记录发作间期和发作期脑电图,以判断致疒间皮质,并采用皮质电刺激行脑功能区定位,在指导术中尽可能切除致疒间皮质的同时,最大限度保护脑功能。结果癫疒间发作起始区切除2例,癫疒间起始区部分切除加周围皮质热灼5例。随访6个月~1年,术后运动及语言功能均保护良好6例,对侧肢体出现短暂运动障碍后恢复1例。结论颅内电极埋藏与脑功能区定位技术是功能区难治性癫疒间手术必要评估手段,有助于术前明确脑功能区和皮质放电区域,以及两者之间的关系,指导设计手术方式,最大限度提高病人术后生活质量。     

脑膜瘤术后癫(癎)发生的危险因素分析

目的分析脑膜瘤手术后癫疒间发生的危险因素。方法回顾性分析行手术治疗且资料完整的158例脑膜瘤病人的临床资料,以性别、年龄、主要症状、术前癫疒间史、阳性体征、肿瘤部位、手术操作时间、皮质牵拉伤、动静脉损伤、术后血肿、颅内感染、术后水肿、肿瘤切除程度、手术次数、放射治疗、肿瘤复发等16项可能影响因素为自变量,以术后发生癫间疒为因变量,使用Logistic回归分析研究相关的危险因素。结果术前癫间疒史、肿瘤部位、术后水肿、肿瘤切除程度、肿瘤复发等5个因素为脑膜瘤术后癫疒间发生的危险因素。结论脑膜瘤术后癫疒间的发生影响病人生活质量,防治癫疒间发生的危险因素,有望减少脑膜瘤术后癫疒间的发生,改善预后。     

单侧慢性海马电刺激治疗颞叶癫疒间的疗效观察

目的初步探讨单侧慢性海马电刺激治疗颞叶癫疒间的疗效。方法选取经过术前评估认为不适宜行前颞叶切除术的5例颞叶癫疒间病人。癫疒间灶均位于左侧颞叶,其中3例致疒间灶对侧颞叶存在结构性病损,1例对侧颞叶存在功能性异常,1例颞叶病灶累及优势半球侧语言功能区。进一步定位评估单侧颞叶致疒间灶起源,立体定向下向致疒间侧海马头部植入刺激电极,术后进行慢性电刺激,观察控制癫疒间发作的效果及不良反应。结果刺激器埋植术后及慢性电刺激开启后未见明显不良反应。术后随访14~24个月,发作次数平均减少75%1例,50%3例,无明显改善1例。结论对于部分不适合进行前颞叶切除手术的难治性颞叶癫疒间病人,慢性海马电刺激是一项可供选择的治疗方法。     

先天性黑色素细胞痣伴弥漫性黑色素细胞增多症恶性变1例并文献复习

目的探讨先天性黑色素细胞痣(CMN)伴弥漫性黑色素细胞增多症恶性变的治疗方法及效果。方法回顾性分析1例CMN伴弥漫性黑色素细胞增多症恶性变病人的临床资料,行显微手术切除病变组织,送病理检查。并对该病进行文献复习。结果病变达镜下全切除,病理检查结果符合恶性黑色素瘤(MM),综合临床特征,病理诊断考虑为弥漫性黑色素细胞增多症恶性变。病人术后未行进一步治疗,于术后3个月死亡。结论 CMN是一种先天性色斑样痣,仅极少部分可演变为MM和神经皮肤黑色素细胞增多症(NCM)并恶性变,大型CMN病人存在大量复合卫星痣是发生MM和NCM最重要的危险因素。临床上一旦出现颅内MM,治疗应以外科手术为主,放、化疗及免疫治疗仅可使极少部分病人受益,预后极差。     

改良功能性大脑半球切除术治疗婴儿偏瘫伴顽固性癫(癎)(附9例分析)

目的探讨改良功能性大脑半球切除术治疗婴儿偏瘫伴顽固性癫疒间的疗效。方法总结9例小骨窗经侧裂功能性大脑半球切除术病人的临床资料。手术均采用侧裂表面4cm×5cm骨窗开颅,分开侧裂后经皮质进入侧脑室,完成功能性大脑半球切除手术。结果与常规功能性大脑半球切除术相比,手术时间明显缩短(平均4.2h)、术中需要输血比例(22.2%)降低。随访时间平均2.1年,Engel癫疒间疗效分级Ⅰ级6例,Ⅱ级2例,Ⅲ级1例。偏瘫改善6例(66.7%),语言改善5例(55.6%),行为改善8例(88.9%)。结论小骨窗经侧裂功能性大脑半球切除术,癫疒间控制效果满意,且可缩短手术时间,减少术中出血。     

Tau-induced neurodegeneration: mechanisms and targets

The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau’s functions in microtubule assembly and stabilization and with regard to its interactions with other proteins. We describe and analyze important post-translational modifications: hyperphosphorylation, ubiquitination, glycation, glycosylation, nitration, polyamination, proteolysis, acetylation, and methylation. We discuss how these post-translational modifications can alter tau’s biological function. We analyze the role of mitochondrial health in neurodegeneration. We propose that microtubules could be a therapeutic target and review different approaches. Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and propose a mechanism of neurodegeneration.     

The effect of risperidone on reward‐related brain activity is robust to drug‐induced vascular changes

Dopamine (DA) mediated brain activity is intimately linked to reward‐driven cerebral responses, while aberrant reward processing has been implicated in several psychiatric disorders. fMRI has been a valuable tool in understanding the mechanism by which DA modulators alter reward‐driven responses and how they may exert their therapeutic effect. However, the potential effects of a pharmacological compound on aspects of neurovascular coupling may cloud the interpretability of the BOLD contrast. Here, we assess the effects of risperidone on reward driven BOLD signals produced by reward anticipation and outcome, while attempting to control for potential drug effects on regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). Healthy male volunteers (n = 21) each received a single oral dose of either 0.5 mg, 2 mg of risperidone or placebo in a double‐blind, placebo‐controlled, randomised, three‐period cross‐over study design. Participants underwent fMRI scanning while performing the widely used Monetary Incentive Delay (MID) task to assess drug impact on reward function. Measures of CBF (Arterial Spin Labelling) and breath‐hold challenge induced BOLD signal changes (as a proxy for CVR) were also acquired and included as covariates. Risperidone produced divergent, dose‐dependent effects on separate phases of reward processing, even after controlling for potential nonneuronal influences on the BOLD signal. These data suggest the D2 antagonist risperidone has a wide‐ranging influence on DA‐mediated reward function independent of nonneuronal factors. We also illustrate that assessment of potential vascular confounds on the BOLD signal may be advantageous when investigating CNS drug action and advocate for the inclusion of these additional measures into future study designs.     

星形胶质细胞对天冬氨酸特异性半胱氨酸蛋白酶介导β淀粉样蛋白早期突触毒性作用的影响

目的探讨星形胶质细胞(astrocyte,AS)对天冬氨酸特异性半胱氨酸蛋白酶(cysteinyl aspartate specific proteinase,caspase)介导β淀粉样蛋白(β-amyloid,Aβ)早期突触毒性作用的影响,以期为进一步研究与血管性痴呆(vascular dementia,Va D)的发病机制奠定基础。方法以原代培养大鼠海马纯神经元体系(NE-S)及混合培养体系(MIX-S,主要包含神经元及AS)为研究对象,各体系分为6组:对照组、caspase-8抑制剂组、caspase-9抑制剂组、Aβ处理组、caspase-8抑制剂预处理加Aβ组和caspase-9抑制剂预处理加Aβ组。免疫荧光检测各组近胞体10μm段树突中突触后密度蛋白(postsynaptic density-95,PSD95)表达量的变化。结果 1在NE-S与MIX-S中,与对照组相比,caspase-8抑制剂组、caspase-9抑制剂组PSD95的表达量均无明显差异,Aβ处理组PSD95的表达量均显著降低(P均0.001)。2在NE-S中,与Aβ处理组相比,caspase-9抑制剂预处理加Aβ组PSD95的表达量显著回升至对照组水平,caspase-8抑制剂预处理加Aβ组则无显著改变;在MIX-S中的结果则相反,即caspase-8抑制剂预处理加Aβ组PSD95的表达量显著回升至对照组水平,而caspase-9抑制剂预处理加Aβ组则无显著改变。3MIX-S与NE-S两种培养系统间相比较,对照组间及Aβ处理组间PSD95的表达量均无显著差异,而caspase-8抑制剂预处理加Aβ组间及caspase-9抑制剂预处理加Aβ组间PSD95的表达量差异有显著性。结论在Aβ早期突触毒性作用中,AS参与caspase-8介导的死亡受体通路激活过程,且参与抑制神经元的线粒体通路。     

Ultrastructure of non-myelinated neurons during energy deprivation

Summary This paper examines the neuropathology of oxygen-glucose deprivation uncomplicated by stagnant conditions. Rabbit vagus nerves were pulled into asmulti-compartment perfusion chamber, stimulated five times per second and deprived of energy by substituting nitrogen and deoxyglucose for oxygen and glucose in the Locke's perfusate. After incubation the compartments were perfused with gluteraldehyde solution, and the nerves were prepared for electron microscopy. Fixation in the compartments ensured precise cross and longitudinal sections which permitted quantitative comparisons. Although the action potentials ceased in 45 min, 1 h of energy deprivation did not significantly affect the ultrastructure. After 2 h of deprivation the axons were smaller and flattened and microtubules appeared packed together. In the smallest axons the microtubules were gone, the neurofilaments were compacted and the few mitochondria had a dense, homogenous appearance. By 4 h the shrinking was extreme, yet 8% were swollen much larger than any of the controls. Longitudinal views showed these balloned areas were greatly expanded regions of the smallest axons. Both tiny and huge regions were devoid of microtubules and the swollen axons contained expanded mitochondria.Calcium is indirectly implicated in the pathogenesis by the concurrence of mitochondrial alteration as the microtubules disappear coupled with the known role of mitochondria in calcium regulation and the reported effect of high calcium on microtubual dissociation. In is suggested that axons first shrink as osmotially active molecules are used or washed out. After a time without energy the mitochondria can no longer regulate the intracellular calcium, microtubules dissociate, and calcium-activated phospholipases create osmotically active molecules. Finally, high-amplitude, disruptive swelling occurs.Supported, in part, by a Grant-in-aid from the American Heart Association with funds contributed by the American Heart Association, Kansas Affiliate and by the University of Kansas Biomedical Sciences Support Grant RR0737     

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

Positron emission tomography (PET) is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including genetically-engineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.     

Norharman-induced motoric impairment in mice: neurodegeneration and glial activation in substantia nigra

Summary. The β-carboline norharman is present in cooked food and tobacco smoke and show structural resemblance to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. C57BL/6 mice were injected subcutaneously with norharman (3 and 10 mg/kg) twice per day for five consecutive days. Eighteen hours after the last dose an increased expression of glial fibrillary acidic protein and fluoro-jade staining were demonstrated whereas the number of tyrosine hydroxylase positive cells were unchanged in the substantia nigra. Two weeks after the last treatment a decreased motor activity was observed whereas cognitive functions remained intact. In cultured PC12 cells norharman treatment induced mitochondrial dysfunction and increased the number of caspase-3 and TUNEL-positive cells. The results demonstrate that norharman induced apoptosis in cultured cells as well as early neurodegeneration, glial activation and sustained motor deficits in mice and suggest that exposure to norharman may contribute to idiopathic Parkinson’s disease.     

轻型缺血性卒中静脉溶栓后双重抗血小板疗效观察

目的 观察rt-PA静脉溶栓联合双重抗血小板治疗轻型缺血性卒中的有效性及安全性。 方法 以2013年12月-2016年12月在石家庄市第一医院连续住院治疗的轻型缺血性卒中患者为研究 对象,将其随机分为对照组、溶栓+单抗组和溶栓+双抗组。对照组不进行静脉溶栓,长期口服阿 司匹林（100 mg/d）抗血小板治疗;溶栓+单抗组在rt-PA静脉溶栓（0.9 mg/kg,最大剂量90 mg）基 础上长期单用阿司匹林（100 mg/d）抗血小板治疗;溶栓+双抗组在溶栓后单抗基础上加用氯吡格雷 （75 mg/d）双重抗血小板治疗,双抗治疗21 d后改为阿司匹林长期单抗治疗。随访3个月,有效性指标 为3个月时NIHSS 0～1分、Barthel指数（Barthel index,BI）95～100分和mRS 0～1分的比例,3个月时缺 血性卒中的复发率;安全性指标为治疗24 h出血转化和症状性出血转化的发生率。另外比较三组间 基线和3个月时血清hs-CRP和IL-6的水平差异。 结果 研究共纳入85例患者,对照组28例,溶栓+单抗组28例,溶栓+双抗组29例,全部患者均完 成3个月随访,无死亡患者。对照组、溶栓+单抗组和溶栓+双抗组3个月随访时NIHSS 0～1分比例分 别为46.43%、78.57%和93.10%,BI 95～100分比例分别为53.57%、82.14%和89.66%,mRS 0～1分 的比例分别为50.00%、82.14%和93.10%,三组上述有效性指标差异均有统计学意义,两两比较显 示,溶栓+双抗组高于溶栓+单抗组和对照组,溶栓+单抗组高于对照组,差异均有统计学意义;对 照组、溶栓+单抗组和溶栓+双抗组3个月时缺血性卒中复发率分别为32.14%、7.14%和3.45%,差异 有统计学意义。安全性指标方面,三组均无出血转化事件。对照组、溶栓+单抗组和溶栓+双抗组3 个月时的hs-CRP水平分别为11.92±3.58 mg/L、9.04±2.85 mg/L和6.04±2.65 mg/L,IL-6水平分别为 26.18±4.65 ng/L、16.11±6.93 ng/L和12.84±2.57 ng/L,三组上述炎症因子水平差异均有统计学意 义,其中溶栓+双抗组低于溶栓+单抗组和对照组,溶栓+单抗组低于对照组。 结论 对于急性轻型缺血性卒中患者,rt-PA静脉溶栓治疗后短期双重抗血小板治疗可显著改善患 者神经功能,降低炎症因子水平,降低复发率,且不增加出血风险。     

The ENIGMA‐Epilepsy working group: Mapping disease from large data sets

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy.     

缺血性卒中并发2型糖尿病患者颈动脉斑块内新生血管分布特点的超声造影研究

目的 应用超声造影观察缺血性卒中并发2型糖尿病患者颈动脉斑块内新生血管分布情况,明确其 斑块内新生血管分布特征。 方法 病例组选取因急性缺血性卒中住院的糖尿病患者40例（入组前未服用降糖药）,卒中同侧颈 动脉斑块形成;对照组为同期门诊就诊的颈动脉斑块形成患者,无卒中病史,性别及年龄匹配的非 糖尿病患者32例。两组患者行弓上计算机断层扫描血管造影（computed tomography angiography,CTA） 检查排除主动脉弓斑块及颅内动脉病变,排除卵圆孔未闭及心房颤动等。对所有患者均行常规超声 及超声造影检查。常规超声观察斑块厚度及内部回声,超声造影观察斑块增强情况,横切面多角度 观察,将超声造影结果分为近内膜处有增强（代表新生血管）及近内膜处无增强两种。 结果 两组患者颈动脉斑块厚度及回声情况差异无统计学意义。超声造影结果显示病例组颈动脉 斑块近内膜处增强者34例（85%）,对照组近内膜处增强12例（37.5%）,差异有统计学意义（χ 2=17.38, P＜0.01）。 结论 未服用降糖药的2型糖尿病并发急性缺血性卒中的患者颈动脉粥样硬化斑块内近内膜处新生 血管增生多于无糖尿病患者,提示血糖升高与颈动脉斑块内血管新生有关。     

Yohimbine increases the binding potential for [11C]flumazenil in the monkey brain

Summary. We evaluated the impact of yohimbine administration on benzodiazepine (BDZ) receptor binding in the central nervous system of non-human primates (rhesus monkeys). Estimates of the binding potential (B_max/K_d) of BDZ receptors were made following intravenous administration of yohimbine, an α₂-adrenoceptor antagonist. Positron emission tomography was used in conjunction with [¹¹C]flumazenil (Ro 15-1788), a tracer for central BDZ receptor binding activity. The effects of yohimbine were compared with a control condition in which saline was administered. Yohimbine significantly increased the binding potential in the hippocampus, as assessed using a Student's t-test with Bonferroni correction. The result that the administration of yohimbine readily induces an increase in the binding potential for BDZ receptors in the primate brain suggests that the presence of an anxiety state potentiates the effect of anxiolytics. Accepted August 10, 2001