Wilson病患者眼区情绪认知障碍的研究

目的探讨Wilson病(Wilson disease,WD)患者是否存在眼区情绪认知障碍,了解基底节有无参与眼区情绪认知加工过程。方法将32例WD患者以及29名与其人口学资料相匹配的健康人(healthy control,HC)作为被试,采用眼区的6种基本情绪(喜、惊、恐、悲、厌、怒)任务,对两组进行测试。结果与HC组比较,WD组在在眼区情绪认知任务对怒(17.53±1.39分,P<0.05),恐(15.88±1.21分,P<0.05)和厌(18.00±1.85分,P<0.001)眼区情绪认知存在明显障碍;而对于喜、惊、悲的眼区情绪认知任务识别却无障碍(均P>0.05)。结论WD患者存在明显的怒、恐及厌眼区情绪认知障碍,基底节可能参与眼区情绪认知任务的加工过程。     

肝移植与Wilson病

Wilson病（Wilson disease，WD）是神经科较为常见的以铜代谢障碍为特征的单基因常染色体隐性遗传病，以青霉胺为代表的驱铜药物是目前WD最主要的对症治疗手段，但其对终末期WD治疗效果差，也无法挽救首发表现为暴发性肝功能衰竭的WD患者的生命。自1969年DuBois等首次为WD患者成功实施肝移植手术以来，包括我国在内已有数百名WD患者接受了这一手术，肝移植为WD的治疗带来了新的希望。有些移植中心报道肝移植能够逆转WD的临床症状、体征及铜代谢障碍，并有长期乐观的预后”。     

Wilson病患者心理理论障碍的研究

目的探讨Wilson病(WD)患者的心理理论(ToM)障碍。方法对32例WD患者(WD组)以及29名健康人(NC组)进行认知功能及失言识别和眼区基本情绪辨别(喜、惊、恐、悲、厌、怒)评分,并对结果进行比较。结果与NC组比较,WD组的简易精神状态检查量表、智商、言语流畅性测试和数字广度评分差异无统计学意义。与NC组比较,WD组失言识别及心理状态判断评分显著降低(均P<0.01);眼部情绪辨别中的怒、恐和厌的评分显著降低(P<0.05～0.01),而喜、悲和惊的评分差异无统计学意义。结论 WD患者存在明显的ToM障碍,可能与其基底节损害有关。     

脑型Wilson病患者认知功能障碍与负性情绪研究

目的 分析脑型WD患者的认知功能损害与负性情绪的特点.方法 对30例脑型WD患者和30例对照者组采用简易智能量表(MMSE)、MoCA量表进行认知功能评估.采用抑郁自评量表(SDS)和焦虑自评量表(SAS)进行情绪状态评估,并进行分析.结果 脑型WD患者组MMSE、MoCA量表评分均较正常组低,差异具有统计学意义(P<0.05);脑型WD患者组SDS评分和SAS评分均较正常组高,差异有统计学意义(P<0.01).结论 脑型WD患者存在认知功能损害和明显的抑郁和焦虑情绪.神经精神量表是客观的评价脑型WD患者神经心理状况的有效手段.     

厌恶情绪加工神经机制的研究

目的探讨岛叶、基底节卒中患者的情绪认知特征,验证这些脑结构参与情绪加工以及厌恶的特异性神经机制的假说。方法测试2例岛叶损伤患者(例1、例2)、32例基底节卒中患者(基底节梗死或出血)和30名健康对照组的6种基本情绪(喜、惊、怕、悲、厌、怒)和中性情绪的面孔表情以及声音辨认能力。结果与相应对照组比较(厌恶面孔和厌恶声音的正确得分为14.65±2.25、17.61±3.12),例1、例2对厌恶声音和厌恶面孔的辨别均有障碍(厌恶面孔识别正确得分分别为7、9,厌恶声音识别正确得分分别为7、8,P<0.01)。而基底节卒中患者主要表现厌恶面孔辨别障碍(正确得分为10.42±2.71,P<0.01),对厌恶声音辨别正常,但表现为“怕”和“怒”的辨别障碍(正确得分为11.00±2.31、13.30±2.75,P<0.05)。结论基底节可能选择性参与厌恶情绪的视觉加工,而岛叶则选择性参与了厌恶情绪视觉和听觉通道的加工。岛叶-基底节系统在厌恶情绪加工中起着重要作用。     

肝豆状核变性的治疗进展

肝豆状核变性（hepatolenticular degeneration，HLD）亦称Wilson病（Wilson disease，WD），好发于青少年，呈常染色体隐性遗传，由于铜代谢障碍导致铜离子在机体各脏器异常沉积引起多系统损害。主要病理改变为肝硬化及豆状核变性。不同地区、种族及个体差异，铜离子沉积的速度、部位及程度有所不同。临床表现复杂多样，主要表现为肝脏损害、神经精神功能障碍、肾脏损害及角膜K—F环；生化特征表现为血浆铜蓝蛋白及血清铜离子水平低下，24h尿铜排出量增加。[第一段]     

肝豆状核变性诊断与治疗中需注意的问题

肝豆状核变性（亦称Wilson病）是以铜离子代谢障碍为特征的神经遗传性疾病，遗传方式为常染色体隐性遗传。其发病机制是由于Wilson基因（13q4．1）突变致该基因编码的蛋白质（ATPTB蛋白或ATP7B酶）发生改变，引起血浆铜蓝蛋白（ceruloplasmin，CP）合成减少和胆管排铜障碍，使铜离子在肝、脑（尤其是基底节）、肾、角膜等组织中沉积；临床表现为肝硬化、锥体外系症状、肾功能损害、角膜K—F环等。肝豆状核变性好发于青少年，亚洲国家（中国、韩国、日本、印度等）发病率明显高于欧美等西方国家，据我院李洵桦等统计，肝豆状核变性占我院神经遗传病门诊的10．14％，仅次于Duchenne型肌营养不良症（DMD）。[第一段]     

X-连锁隐性遗传肌张力障碍一家系10例

原发性肌张力障碍（idiopathic torsion dystonia，ITD）是指因持续性肌肉收缩而引起的肢体扭曲或重复运动综合征，是全身性肌张力障碍的一种表现。ITD是一种遗传病，可分为常染色体显性、常染色体隐性和X-连锁隐性遗传。ITD在犹太人中发病率可高达1／15000，在非犹太人群则为1／200000。国内曾有常染色体显性遗传肌张力障碍家系的报道，而X-连锁隐性遗传肌张力障碍（X-linked dystonia parkinsonism，XDP）未见报道。我科于2004年9月收治了1例XDP患者，现将该家系报道如下。     

肝豆状核变性一家3例报告

患者．男．18岁，因黑便6天、呕血2次住院。入院前6天无诱因黑便1次，柏油状，量约200ml，未介意，此后每日排柏油便2～3次。入院前1d因进食油炸鱼突发呕血2次，鲜红色，带血块．总量约600ml。伴头晕、乏力、心悸，无腹疼．无返酸、嗳气。10年前因尿黄、纳差诊断为“病毒性肝炎”住院治     

Wilson病患者的铁代谢相关指标研究

目的:研究Wilson病(WD)患者的血清铁代谢相关指标水平.方法:选取未接受过正规驱铜治疗的WD患者103例(WD组),WD组再依据MRI异常分为3个亚组:WD-MRI无异常组、WD-MRI长T2组和WD-MRI短T2组.另选取健康志愿者25名(正常对照组)和乙肝患者18例(乙肝对照组)为研究对象.WD组患者于入院时进行血清铜蓝蛋白以及血清铁代谢指标测定;正常对照组及乙肝对照组均检测铁代谢指标.结果:WD各亚组高铁铁蛋白水平与正常对照组比均显著增高,差异有统计学意义(P<0.05);与乙肝对照组比较则显著降低(P<0.01).WD组转铁蛋白明显降低,与正常对照组和乙肝对照组比较,均差异有显著统计学意义(均P<0.01).WD各亚组的人转铁蛋白受体与乙肝对照组比较,差异有显著统计学意义(P<0.01);乙肝对照组与正常对照组比较,差异有显著统计学意义(P<0.01).结论:WD患者存在铁代谢异常,但不同于乙肝对照组的人转铁蛋白受体高表达,可能是转铁蛋白的低调节所致.     

Impairment of recognition of disgust in Chinese with Huntington's or Wilson's disease

The selective involvement of the basal ganglia in recognition of the facial expression of disgust was investigated by examining a group of six symptomatic Huntington's disease patients and 32 Wilson's disease patients in China. Morphed photographs of facial expressions covering happiness-surprise-fear-sadness-disgust-anger were used and the patients were asked to label each photo. Other measures assessed basic cognitive functions and perception of non-emotion facial information, such as perception of gender, age, gaze direction, and recognition of unfamiliar as well as famous people. There was dissociation between the perception of emotions and other facial information, and between impairment of recognition of disgust and other emotions. The basal ganglia are the overlapping substrate involved in both Huntington's and Wilson's disease, although each has its own other lesions. The differentially severe impairment of recognition of disgust in the Chinese Huntington's disease and Wilson's disease patients strengthens the view that basal ganglia are selectively involved in processing the emotion of disgust.     

No disgust recognition deficit in obsessive-compulsive disorder

BACKGROUND: Patients with basal ganglia abnormalities misclassify facial expressions of disgust as expressions of anger when asked to identify the emotion depicted in photographs of individuals displaying different emotions. Sprengelmeyer, Young, Pundt et al. (1997) reported a similar disgust recognition deficit in patients with obsessive-compulsive disorder (OCD)--an anxiety disorder associated with basal ganglia abnormality. METHODS: In the present experiment, we attempted to replicate Sprengelmeyer, Young, Pundt et al.'s (1997) findings. RESULTS: We failed to replicate Sprengelmeyer, Young, Pundt et al.'s finding of disgust recognition deficits in OCD patients relative to healthy control subjects. One patient with especially severe OCD did, however, exhibit impairment by misclassifying disgust expressions as anger expressions. DISCUSSION: These data do not confirm the presence of disgust recognition deficits in individuals with OCD. In light of the deficits exhibited by one subject with severe OCD, disgust recognition deficits may be confined to an unidentified subset of people with OCD.     

Wilson病ATP7B基因重组腺病毒载体Ad-ATP7B的构建

目的 构建Wilson病基因ATP7B的重组腺病毒载体。方法 分别以BamHⅠ SalⅠ双酶切pcDNA3．0／ATP7B和pDC315，将ATP7BcDNA目的基因片段和线性化的pDC315连接，定向克隆构建pDC315／ATP7B，以PCR和酶切的方法鉴定。pDC315／ATP7B与腺病毒骨架共转染293细胞构建Ad-ATP7B，PCR进行鉴定。结果 经PCR和酶切鉴定证实pDC315／ATP7B构建成功。pDC315／ATP7B与腺病毒骨架共转染293细胞后见明显的毒斑，说明二者在293细胞中同源重组并包装成功。经PCR证实重组腺病毒Ad-ATP7B构建已完成。结论 本实验成功构建了ATP7B外源目的基因序列完全正确的重组腺病毒载体Ad-ATP7B，为下一步采用ATP7B基因重组腺病毒载体对Wilson病进行基因治疗打下了基础。     

Recognition of disgust is selectively preserved in Alzheimer's disease

The neural substrates that subserve decoding of different emotional expressions are subject to different rates of degeneration and atrophy in Alzheimer's disease (AD), and there is therefore reason to anticipate that a differentiated profile of affect recognition impairment may emerge. However, it remains unclear whether AD differentially affects the recognition of specific emotions. Further, there is only limited research focused on whether affect recognition deficits in AD generalize to more ecologically valid stimuli. In the present study, relatively mild AD participants (n = 24), older controls (n = 30) and younger controls (n = 30) were administered measures of affect recognition. Significant AD deficits were observed relative to both the younger and older control groups on a measure that involved labeling of static images of facial affect. AD deficits on this measure were observed in relation to all emotions assessed (anger, sadness, happiness, surprise and fear), with the exception of disgust, which was preserved even relative to the younger adult group. The relative preservation of disgust could not be attributed to biases in the choice of labels made, and it is suggested instead that this finding might reflect the relative sparing of the basal ganglia in AD. No significant AD effect was observed for the more ecologically valid measure that involved dynamic displays of facial expressions, in conjunction with paralinguistic and body movement cues, although a trend for greater AD difficulty was observed.     

74例肝豆状核变性患者中ATP7B基因七种新突变的发现

目的 分析中国人肝豆状核变性（Wilson disease,WD）患者ATP7B基因突变的分布特征,建立利用变性高效液相色谱（DHPLC）技术对Wilson病进行基因诊断的方法,并评价其在临床的应用价值.方法 对临床确诊为Wilson病的74例患者及50名健康人抽取外周静脉血提取基因组DNA.以患者和健康人的DNA为模板,分别对ATP7B基因的21个外显子进行PCR扩增.取PCR产物应用DHPLC技术在部分变性条件下检测突变并DNA测序证实突变位点.结果 利用DHPLC技术筛查并经测序证实,共发现22种ATP7B基因突变类型,其中7种是新发现的,同时发现11种多态,其中3种是新发现的.第8外显子Arg778Leu突变率最高,其频率为25.0%.其次,2356-2A＞G突变频率为3.4%,Arg919Gly突变频率为2.7%,其他外显子突变频率均在1.0%～2.0%之间.结论 中国人的WD基因突变具有多样性特点,热点突变是第8外显子Arg778Leu.DHPLC具有高通量、敏感、准确且经济的特点,适合于大样本的筛查且能够发现未知的突变,是一种有临床应用价值的基因诊断技术.     

The interhemispheric connections of the striatum: Implications for Parkinson's disease and drug-induced dyskinesias

Parkinson's disease (PD) is characterized by loss of nigrostriatal neurons and depletion of dopamine. This pathological feature leads to alterations to basal ganglia circuitry and subsequent motor disability. Pharmacological dopamine replacement therapy with medications such as levodopa ameliorates the symptoms of PD but can lead to motor complications known as drug-induced dyskinesias. We have recently shown that clinically hemiparkinsonian rhesus monkeys do not develop levodopa-induced dyskinesias despite chronic intermittent exposure and significant unilateral loss of nigrostriatal neurons and dopamine. It is currently unclear what mechanisms prevent the onset of dyskinesias in these animals. Based on our study and results from previous lesioning studies in both the rat and monkey models of PD, we hypothesize that one potential mechanism that may prevent the genesis of dyskinesias in these animals is interhemispheric neuromodulation. Two potential interhemispheric connections that may modulate dyskinesias are the interhemispheric nigrostriatal and corticostriatal pathways. Few investigators have examined the interhemispheric nigrostriatal and corticostriatal connections and the functional role they may play in drug-induced dyskinesias in PD. Therefore, in the following review, we assess the neuroanatomical, electrophysiological and behavioral properties of these interhemispheric connections. Future studies evaluating these interhemispheric striatal pathways and the pathophysiological changes that occur to these pathways in the dyskinetic state are warranted to further develop treatments that prevent or mitigate drug-induced dyskinesias in PD.     

Kinematic properties of slow arm movements in Parkinson's disease

Present pathophysiological concepts of bradykinesia stress an impairment of fast movements in Parkinson's disease. It is, however, unknown whether bradykinetic movements are different from slow movements of normal subjects. We recorded trajectories of unrestrained natural arm movements from normal subjects and patients with Parkinson's disease. The experiment required the execution of pointing movements for different movement distances and velocities. The shape of trajectories was found to be changed in Parkinson's disease. The steepness of the initial segment and the relation between steepness of the initial segment and final segment both exceeded corresponding values in normal subjects. An analysis of velocity profiles showed an impaired synchrony of vertical and horizontal velocity components. The difference from normal subjects increased with movement velocity. Parkinsonian patients suffered from a fundamental defect in the composition of complex sequences of motor programs required to perform natural arm movements.     

肝豆状核变性睡眠障碍初步研究

目的探讨肝豆状核变性(HLD)患者睡眠障碍特点及其潜在发生机制。方法采用帕金森病睡眠量表(PDSS)、Epworth嗜睡量表(ESS)和匹兹堡睡眠质量指数(PSQI)评价26例肝豆状核变性患者的睡眠障碍。结果 HLD组患者PDSS总评分低于对照组(P=0.000),其中,夜间总体睡眠质量(P=0.010)、入睡困难(P=0.009)、睡眠维持困难(P=0.013)、震颤(P=0.005)、清晨醒后感觉困倦欲睡(P=0.042)和白天过度嗜睡(P=0.028)等分评分亦低于对照组;而ESS(P=0.009)和PSQI(P=0.005)评分高于对照组。进一步分析肝豆状核变性各亚组患者睡眠障碍,脑型HLD组PDSS总评分低于肝型HLD组和无症状型HLD组(P=0.046),其中,夜间总体睡眠质量(P=0.021)、入睡困难(P=0.009)和睡眠维持困难(P=0.002)等分评分亦低于肝型HLD组和无症状型HLD组。结论肝豆状核变性患者常合并睡眠障碍且以入睡困难、夜间觉醒和白天过度嗜睡为主,其中脑型肝豆状核变性患者睡眠质量差于肝型和无症状型患者。肝豆状核变性睡眠障碍的发生机制尚待进一步研究。