丘脑底核脑深部电刺激治疗帕金森病的临床分析

目的:通过丘脑底核脑深部电刺激术治疗帕金森病,观察其肌肉僵直、静止性震颤、运动迟缓等症状的改善情况。方法:选取以丘脑底核为刺激靶点收治的帕金森病患者8例,对比手术前后患者肌强直、静止性震颤、运动迟缓等症状的改善情况,并进行UPDRS评分。结果:接受丘脑底核脑深部电刺激术治疗帕金森病6个月后,患者肌肉僵直、静止性震颤、运动迟缓等临床主症的改善上效果良好;与手术前相比,患者术后UPDRS评分均有所降低,差异具有统计学意义(P0.05);患者术后美多巴服用量显著减少,差异具有统计学意义(P0.05);患者术后没有产生永久性的并发症以及较明显的临床症状;但对大量油脂性渗出及典型面具性面容的治疗上未见明显疗效。结论:丘脑底核脑深部电刺激术治疗帕金森氏病,可以使帕金森病主要临床症状肌肉僵直、静止震颤及运动迟缓得到明显改善,显著减少美多巴服药量,具有安全可靠的疗效,对临床具有指导意义,值得临床推广应用。     

脑深部电刺激的研究现状

脑深部电刺激是近年来神经中枢疾病治疗的一项新技术,具有可逆性、参数可调、对组织非破坏性等特点.目前,脑深部电刺激的治疗对象主要有帕金森症患者、癫痫患者以及各种难治性疼痛患者.本文综述了脑深部电刺激的概念、原理、优缺点,并对临床应用现状和应用前景进行了分析.     

脑深部电刺激自身给药大鼠伏隔核区△FosB的表达

目的:对吗啡依赖大鼠实施双侧伏隔核脑深部电刺激(NAc-DBS),分析NAc区△FosB的表达变化,为NAc-DBS治疗药物依赖提供分子生物学证据.方法:18只大鼠随机分为三组,包括DBS组(n=6,实施颈静脉插管和电板植入手术,吗啡给药,DBS),Sham组(n=6,实施颈静脉插管和电极植入手术,吗啡给药),Control组(n=6,实施颈静脉插管和电极植入手术,给予生理盐水),观察DBS组大鼠在高频电烈激期(160 Hz,1 h/d,7d)的觅药行为变化,然后进行取脑,切片,免疫组化染色,观察伏隔核区△FosB的表达.结果:成瘾大鼠在高频电刺激期,觅药行为明显减少;免疫组化染色后观察到DBS组大鼠NAc区△FosB的表达相对于Sham和Control组明显减少.结论:双侧NAc-DBS抑制吗啡成瘾大鼠的觅药行为以及NAc区△FosB的表达,证实△FosB可能是慢性成瘾转换机制的关键分子的观点.     

深部脑刺激的工作原理

深部脑刺激器是一种体内植入型治疗设备．它能连续不断地传送刺激脉冲到深部脑组织区域，这种作用称为深部脑刺激。神经外科医生通常会用深部脑刺激来治疗各种抗药性运动障碍疾病，如帕金森氏症、原发性震颤及肌张力异常等，但科学家们一直不清楚刺激作用改善疾病症状的机理。     

经颅磁刺激对癫痫病灶脑电相关维数的影响

利用脑功能指标——大鼠病灶区脑电的相关维数,研究低频经颅磁刺激对慢性颞叶癫痫大鼠脑功能改善的作用。对一组颞叶癫痫大鼠施予频率为0．5Hz、强度为0．4T、20次／日、连续一周的低频重复性经颅磁刺激(rTMS)．在rTMS前后,分别测取颞叶癫痫大鼠责任病灶区皮层和海马区的脑电,重构时间延迟吸引子,用G-P算法估算反映对应脑区功能状态的相关维数。研究结果显示：施予适量的rTMS(0.4T、20次／日、连续一周),使颞叶癫痫大鼠海马和相应皮层脑电的相关维数比刺激前明显升高。研究表明适量的rTMS有抑制癫痫的作用。     

深部脑刺激对大鼠丘脑底核神经活动的影响

为了探求高频电刺激对受刺激核团的影响,在高频刺激丘脑底核的同时,同步记录了大鼠丘脑底核神经元活动．针对同步记录中刺激伪迹的难题,研究并应用了高效的刺激伪迹滤出算法,恢复了被掩盖的神经响应,且失真小．研究了刺激幅度、频率与神经元神经响应类型的关系,以及在临床治疗有效刺激参数下,高频刺激对神经元平均放电率的影响．研究结果显示,放电率的变化可能与帕金森症病理状态无直接关系,爆发式放电增多更可能是帕金森发病潜在的电生理基础,而受刺激核团的自发放电的抑制、放电率的降低及爆发式放电的减少则有可能是深部脑刺激作用机制的一部分．     

新型深部脑刺激模式的开发及研究进展

深部脑刺激(deep brain stimulation,DBS)已成为治疗帕金森病等运动障碍疾病的常规方法之一,并且在许多其他神经和精神疾病的治疗中也具有良好的应用前景.但是,目前常规DBS采用单通道恒定脉冲间隔的高频刺激(high frequency stimulation,HFS),刺激模式缺少多样化,限制了DBS在临床上的推广应用.为了开发更多DBS刺激模式,用于改善疗效、拓展应用范围、并节省刺激器的电能,近年来研究人员基于去同步调控机制,在脉冲序列的时间模式和空间排布两方面开发了DBS新模式.主要包括:变频序列(包括规则变频和随机变频)、不同空间位点上的多通道异步刺激以及变频和多通道两者的结合.这些新刺激模式能够提高DBS的临床疗效、降低刺激能耗,在帕金森病以及癫痫、强迫症和微意识障碍等其他脑疾病的治疗中都展现了良好的应用前景.更值得关注的是,多通道异步刺激不仅在刺激期间具有更好的即时疗效,而且刺激结束后还能长时间保持疗效,具有刺激后效应.这个特性突破了常规DBS主要为即时效应的局限性,展现了DBS新前景.本文在概述常规DBS模式及其去同步调控机制的基础上,综述变频脉冲刺激和...     

电刺激大鼠右后背海马诱导前背海马神经网络癫痫样电活动

本文旨在探讨单侧海马(hippocampus,HPC)内神经网络与HPC癫痫发生的关系及其细胞机制。实验在45只SSprague-Dawley大鼠上完成。急性强直电刺激大鼠右侧后背HPC CAl基树突区(acute tetanizatio of the posterior dorsal hippocampus,ATPDH;60Hz,2s,0.4-0.6mA)诱发HPC癫痫模型,同步记录同侧前背HPC CAl顶树突区单位放电和基树突区深部电图。结果,ATPDH可以沿长铀向前1．8mm处对前背MIC神经网络产生下述效应：(1)同步或非同步原发性单位与深部电图后放电,在同步性后放电锁时(time-lock)关系明显。非同步性后放电的深部电图癫痫样电活动具有宽频带特征(5-90Hz);(2)原发性单位后放-后抑制效应可以引发低频原发性电图后放电,长时程爆发式单位放电可以诱发高频原发性电图后放电;(3)短束原发性电图后放电也可以诱发原发性单位后放电;(4)原发性电图后放电和神经元单位放电的抑制效应具有明显可塑性特征。以上结果提示,重复施加ATPDH可以引起前背HPC癫痫相关性病理生理性神经网络的重建;而单个神经元与神经网络的异常电活动之间具有明显的互动作用和突触传递可塑性特征;沿HPC长铀内在抑制性通路的过度活动也可以诱发电图癫痫样电活动,导致HPC网络癫痫的发生。     

深部脑刺激作用机制的探讨

深部脑刺激器（deep brain stimulator）,也经常被称为脑起搏器,是可植入人体设备,并连续不断地传送刺激脉冲到深部脑组织的特定区域,即所谓的深部脑刺激（deep brain stimulation,DBS）.迄今为止,深部脑刺激是治疗严重顽固抗药性运动障碍疾病（如帕金森病,原发性震颤及肌张力异常等）的最有效的外科治疗手段之一.此外,广大的科研工作者也不断地探索应用DBS治疗其他神经及精神异常（如,癫痫和强迫症）的新的临床应用.尽管应用DBS治疗运动障碍非常有效,并也迅速被探索性地应用到其他神经障碍治疗中,但其作用机制仍然不是十分清楚,成为学者们争论的热点.DBS治疗效果的作用机制通常有两种基本的观点：高频刺激抑制学说及高频刺激兴奋学说.基于最近发表的关于中枢神经系统内的高频刺激效应的资料、数据及相关评论,两种机制共存并发挥作用的DBS作用假说被提出,认为DBS通过施加高频刺激干扰并控制了核团病理性紊乱随机活动,同时施加兴奋性刺激到其他基底节的网络,以实现对帕金森病的治疗.     

微弱电刺激对失眠者睡眠状况及睡眠脑电影响的初步研究

根据睡眠是由脑内亿万神经元同步振荡所刻划的观点［１］,及各种电刺激对动物睡眠影响的实验［２,３］,设计了用特定θ频率的正弦波微弱电流,刺激失眠病人颈部安眠２穴,以观察其对受试者脑电频率的客观影响。其结果是刺激后失眠病人由醒到２期的脑电记录中,θ波逐渐增加,增加了病人的总睡眠时间。这启示我们这种脑部的特殊频率微弱电流刺激,可能有引起脑部神经元群的共振现象,改变了受试者脑电中频率成分的分布特征,从而有助于失眠的治疗。这一现象是值得进一步研究的。     

Insight and the no‐self in deep brain stimulation

Ethical analyses of the effects of neural interventions commonly focus on changes to personality and behavior, interpreting these changes in terms of authenticity and identity. These phenomena have led to debate among ethicists about the meaning of these terms for ethical analysis of such interventions. While these theoretical approaches have different criteria for ethical significance, they agree that patients’ reports are concerning because a sense of self is valuable. In this paper, I question this assumption. I propose that the Buddhist theory of no‐self offers a novel approach to making ethical sense of patients’ claims following deep brain stimulation. This alternative approach is based on the value of insight into patterns of cause and effect among mental states and actions.     

令人烦恼的记忆

记载着挫折、恐惧、绝望等负性情绪的负性记忆,具有难以遗忘、令人烦恼的特点,与一些脑重大疾病,如创伤后应激综合征、抑郁症等存在密切关系。研究表明NMDA受体依赖性长时程增强在记忆的获取、储存等过程中起着关键作用。电休克和NMDA受体拮抗剂氯胺酮已知可导致短暂性遗忘,应用于治疗创伤后应激综合征、抑郁症具有起效快、疗效好的显著特点,提示这类脑疾病可能与负性记忆的遗忘特点有关。最近报道,遗忘具有独立的分子机理,在记忆和遗忘机理的共同作用下,既可能发生"记不住"如老年痴呆症、也可能出现"忘不了"如创伤后应激综合征和抑郁症等。深入研究遗忘的细胞分子机理,无疑有助于我们认识、预防和治疗相关脑重大疾病。     

New insights offered by a computational model of deep brain stimulation

Deep brain stimulation (DBS) is a standard neurosurgical procedure used to treat motor symptoms in about 5% of patients with Parkinson's disease (PD). Despite the indisputable success of this procedure, the biological mechanisms underlying the clinical benefits of DBS have not yet been fully elucidated. The paper starts with a brief review on the use of DBS to treat PD symptoms. The second section introduces a computational model based on the population density approach and the Izhikevich neuron model. We explain why this model is appropriate for investigating macroscopic network effects and exploring the physiological mechanisms which respond to this treatment strategy (i.e., DBS). Finally, we present new insights into the ways this computational model may help to elucidate the dynamic network effects produced in a cerebral structure when DBS is applied.     

Ethical concerns regarding commercialization of deep brain stimulation for obsessive compulsive disorder

The United States Food and Drug Administration's recent approval of the commercial use of Deep Brain Stimulation (DBS) as a treatment for Obsessive Compulsive Disorder (OCD) will be discussed within the context of the existing USA regulatory framework. The purpose will be to illustrate the current lack of regulation and oversight of the DBS market, which has resulted in the violation of basic ethical norms. The discussion will focus on: 1) the lack of available evidence on procedural safety and efficacy, 2) the numerous conflicts of interest held by research investigators, and 3) the ambiguity of both aforementioned categories due to an inherent lack of transparency in the research. It is argued that in order to address these issues, ethical analyses of DBS for psychiatric disorders must include the role of the industry forces that have become the primary impetus for this research. As such, DBS for OCD serves as an important case example in studies of neurotechnology and innovative surgery.     

老年痴呆患者生活质量及其影响因素分析研究

目的:研究老年痴呆患者生活质量并分析其影响因素。方法:收集2009年1月至2013年8月我院收治的符合标准的老年痴呆患者232例记为病例组,另选取300例正常老年人作为对照组,运用老年痴呆生活质量量表(QOL-AD)评价其生活质量,并运用多元逐步回归分析分析影响生活质量的因素。结果:与对照组相比,病例组QOL-AD的13项评分均低于对照组,差异有统计学意义(P0.05)。多元逐步回归分析显示年龄、照顾者、居住情况是老年痴呆患者生活质量的影响因素(P0.05)。结论:老年痴呆患者生活质量差,受多因素影响,应采取综合措施改善老年痴呆患者的生活质量。     

Stimulating personality: Ethical criteria for deep brain stimulation in psychiatric patients and for enhancement purposes

Within the recent development of brain-machine-interfaces deep brain stimulation (DBS) has become one of the most promising approaches for neuromodulation. After its introduction more than 20 years ago, it has in clinical routine become a successful tool for treating neurological disorders like Parkinson's disease, essential tremor and dystonia. Recent evidence also demonstrates efficacy in improving emotional and cognitive processing in obsessive-compulsive disorder and major depression, thus allowing new treatment options for treatment refractory psychiatric diseases, and even indicating future potential to enhance functioning in healthy subjects. We demonstrate here that DBS is neither intrinsically unethical for psychiatric indications nor for enhancement purposes. To gain normative orientation, the concept of “personality” is not useful – even if a naturalistic notion is employed. As an alternative, the common and widely accepted bioethical criteria of beneficence, non-maleficence, and autonomy allow a clinically applicable, highly differentiated context- and case-sensitive approach. Based on these criteria, an ethical analysis of empirical evidence from both DBS in movement disorders and DBS in psychiatric disease reveals that wide-spread use of DBS for psychiatric indications is currently not legitimated and that the basis for enhancement purposes is even more questionable. Nevertheless, both applications might serve as ethically legitimate, promising purposes in the future.     

The epigenetic component of the brain response to electromagnetic stimulation in Parkinson's Disease patients: A literature overview

Modulations of epigenetic machinery, namely DNA methylation pattern, histone modification, and non‐coding RNAs expression, have been recently included among the key determinants contributing to Parkinson's Disease (PD) aetiopathogenesis and response to therapy. Along this line of reasoning, a set of experimental findings are highlighting the epigenetic‐based response to electromagnetic (EM) therapies used to alleviate PD symptomatology, mainly Deep Brain Stimulation (DBS) and Transcranial Magnetic Stimulation (TMS). Notwithstanding the proven efficacy of EM therapies, the precise molecular mechanisms underlying the brain response to these types of stimulations are still far from being elucidated. In this review we provide an overview of the epigenetic changes triggered by DBS and TMS in both PD patients and neurons from different experimental animal models. Furthermore, we also propose a critical overview of the exposure modalities currently applied, in order to evaluate the technical robustness and dosimetric control of the stimulation, which are key issues to be carefully assessed when new molecular findings emerge from experimental studies. Bioelectromagnetics. 39:3–14, 2018. © 2017 Wiley Periodicals, Inc.     

Intracerebral quantitative chromophore estimation from reflectance spectra captured during deep brain stimulation implantation

Quantification of blood fraction (f_blood), blood oxygenation (S), melanin, lipofuscin and oxidised and reduced Cytochrome aa 3 and c was done from diffuse reflectance spectra captured in cortex, white matter, globus pallidus internus (GPi) and subthalamus during stereotactic implantations of 29 deep brain stimulation (DBS) electrodes with the aim of investigating whether the chromophores can give physiological information about the targets for DBS. Double‐sided Mann‐Whitney U ‐tests showed more lipofuscin in GPi compared to white matter and subthalamus (p < 0.05). Compared to the other structures, f_bloodwas significantly higher in cortex (p < 0.05) and S lower in GPi (p < 0.05). Median values and range for f_blood were 1.0 [0.2–6.0]% in the cortex, 0.3 [0.1–8.2]% in white matter, 0.2 [0.1–0.8]% in the GPi and 0.2 [0.1–11.7]% in the subthalamus. Corresponding values for S was 20 [0–81]% in the cortex, 29 [0–78]% in white matter, 0 [0–0]% in the GPi and 0 [0–92]% in the subthalamus. In conclusion, the measurements indicate very low oxygenation and blood volume for DBS patients, especially in the GPi. It would be of great interest to investigate whether this is due to the disease, the normal situation or an artefact of doing invasive measurements. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)