不宁腿综合征的进展

不宁腿综合征(restless legs syndromes RLS)又称多动腿或不安腿综合征.1685年Thomas Willis首次描述该病的临床特点,1945年Ekbom将其正式命名为不宁腿综合征[1].但迄今为止,人们(包括临床医生)对此病了解甚少.近10年来,众多专家学者基于临床研究和实践相继发表了一些建设性见解,1999年AASM(美国睡眠医学协会)对此作了详尽概述,NIH(美国国立卫生研究院)又发表了专题评述,旨在改善RLS的诊断和治疗.本文就RLS的流行病学、病因和发病机制、临床表现、诊断及治疗作简要综述.     

不安腿综合征最新诊断标准共识

正不安腿综合征(restless legs syndrome,RLS)是一种常见的神经系统感觉运动性疾病,显著影响患者的睡眠及生活质量。1685年Thomas Willis第一次描述了RLS,但直至1945年,Karl-Axel Ekbom才在他的开创性专著"不安腿(Restless Legs)"中提出了诊断标准。为纪念他     

不宁腿综合征的研究进展

不宁腿综合征(RLS)又称不安腿综合征,是一种常见的神经系统疾病,以有强烈活动双下肢的欲望为特征,常伴有感觉异常,症状在休息或夜间时发生或加重,运动后减轻.由于临床医生对其认识不足,常将RLS的感觉运动症状归于失眠、应激、肌肉痛性痉挛、抑郁症、焦虑症等原因,临床上漏诊率和误诊率高.RLS常引起患者睡眠障碍、抑郁症和焦虑症的患病率增高、心血管疾病的风险增加,生活质量受到严重影响.现就RLS的研究进展作一综述.     

不安腿综合征

不安腿综合征（restless legs syndrome，RLS）是一种常见的神经系统感觉运动障碍性疾病，该病可严重影响患者的睡眠，显著降低生活质量。由于该病未引起临床医生重视，常造成误诊或漏诊。我们现就近年来RLS的流行病学、病因、临床表现和诊断、治疗的研究进展作一综述。     

不宁腿综合征40例临床分析

目的 探讨不宁腿综合征(RLS)的临床表现,观察吡贝地尔对RLS的治疗效果.方法 对40例不宁腿综合征患者的临床特征和治疗结果 进行回顾性分析.结果 40例患者均有肢体不能忍受的不适感,迫切希望活动肢体,夜间症状加重,常伴失眠.根据国际不宁腿综合征研究组(IRLSSG)的诊断标准,平均得分24分.40例患者均给予吡贝地尔50mg睡前口服,治疗4周后,大多数患者主观症状明显改善,IRLSSG评分明显减少(平均得分11分).结论 不宁腿综合征常表现下肢不适,夜间加重,活动后减轻,常伴睡眠障碍,诊断主要依据临床表现,吡贝地尔治疗有一定效果.     

不安腿综合征33例报告

目的 进一步探讨不安腿综合征(Restless legs Syndrome，RLS)的临床及预后。方法 对已明确诊断的33例RLS，对其临床及预后作了进一步分析。结果 发现RLS在老年病人中并不少见，多数病人发病找不到任何原因，应用苯二氨罩类药、血管扩张药及抗惊厥药等治疗好转率占90％；无1例死亡。结论 RLS是可以治疗的，预后较好。     

尿毒症合并不安腿综合征患者护理

不安腿综合征又称腿多动症(restless leg syndrome,RLS),是一种常见神经系统感觉运动障碍性疾病,其发病率为3%～15%.主要临床表现为:下肢难以忍受、难以形容的酸困感、蚁走感、虫蚀感、麻木等感觉异常;可伴有烧灼痛、刺痛.感觉异常也可累及上肢,休息时出现或加重,活动后减轻,被迫移动受累肢体可缓解症状.症状呈昼夜节律变化,夜间加重,常常影响睡眠,白天疲乏无力,工作效率低下,生活质量下降,可继发于缺铁性贫血、尿毒症和多发性神经病[1].随着尿毒症人群的不断扩大,RLS人群也不断扩大,但在临床工作中RLS常被忽视.2007-01～2009-03在我院行血液透析的150例患者,出现不安腿综合征16例.现总结护理经验如下.     

不安腿综合征患者伴发的抑郁和焦虑分析

目的了解不安腿综合征（restless legs syndromes,RLS）患者伴发抑郁、焦虑的发病率并分析其相关因素。方法采用抑郁自评量表（SDS）和焦虑自评量袁（SAS）对45例RLS患者和45例对照者进行评定,以国际不安腿综合征评估量表（IRLS）进行评分,评定病情严重程度。结果RLS组抑郁程度明显高于对照组,焦虑标准分明显高于对照组,差异均有统计学意义（P〈0．001）;RLS组抑郁发生率明显高于对照组,焦虑发生率明显高于对照组,且差异显著（P〈0．01）;RLS组抑郁与焦虑共病发生率明显高于对照组,且差异显著（P〈0．05）;经回归分析发现RLS患者伴发的抑郁、焦虑与年龄呈负相关,与IRLS评分呈正相关,与患者的性别、学历、病程无相关性。结论RI。S患者易伴发抑郁和焦虑,应及时发现,尽早干预。     

北京某中学青少年中原发性不安腿综合征患病率调查

目的调查青少年人群中原发性不安腿综合征的患病情况。方法采用问卷调查及电话随访的方式,以国际不安腿综合征研究小组(IRLSSG)制定的4个基本标准进行诊断,并排除继发病因。结果共发放问卷1 568份,有效问卷1500份。第一题答案为"是"的120份,对其进一步电话随访及问卷调查,诊断为原发性RLS共5名(0.33%)。男1名,女4名,年龄14~18岁,平均(16±1.58)岁。患者均无明确家族史,并排除了ADHD等疾病。结论北京市西城区某中学10~20岁青少年中原发性不安腿综合征患病率为0.33%。严重程度为轻中度,均不影响日常生活,未合并情绪异常及睡眠障碍。     

不宁腿综合征11例临床分析

目的探讨不宁腿综合征(RLS)的临床表现及可能的发病机制,观察多巴丝肼对RLS的治疗效果。方法对3年内收治的不宁腿综合征患者11例临床特征和治疗结果进行回顾性分析。结果11例均有活动肢体的迫切愿望,以减轻肢体的不舒服感觉,均在夜间症状加重,其中3例白天也有严重症状。根据国际不宁腿综合征研究组(IRLSSG)的诊断标准,平均得分为24分。经多巴丝肼每晚睡前服用,治疗4周后,多数患者主观症状明显改善,IRLSSG评分明显减少(平均得分14分),其中3例恢复正常。结论多巴丝肼可使RLS临床症状获得明显改善,不良反应较轻,患者依从性好,但长期疗效尚有待于进一步观察。     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

Targeting 13-secretase with RNAi in neural stem cells for Alzheimer＇s disease therapy

There are several major pathological changes in Alzheimer＇s disease, including apoptosis of cho- linergic neurons, overactivity or overexpression of 13-site amyloid precursor protein cleaving enzyme 1 （BACE1） and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein （AI3） production, and introduced it into the pSilenCircle vector to construct a short hairpin （shRNA） expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing AI3 protein production. We anticipate that this technique combining cell transplantation and gene ther- apy will open up novel therapeutic avenues for Alzheimer＇s disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.     

阿尔茨海默病治疗的研究进展

阿尔茨海默病（AD）是一种隐匿性起病,进行性恶化的神经退行性疾病,临床最初表现为认知功能障碍,并有可能在5～10年内完全衰退。患者往往伴随严重的记忆力丧失、精神行为异常、人格改变、言语功能障碍,无法独立生活,最终近乎于植物状态。Ferri等采用DISMOD软件在全球60岁以上人群中估计,全球的痴呆患者人数到2040年将达到8llO万左右。     

Total saponins of Panax ginseng effects on proliferation and differentiation of human embryonic neural stem cells and in a Parkinson’s disease mouse model

BACKGROUND： Total saponins of Panax ginseng （TSPG） exhibits neuroprotection against Parkinson＇s disease in the substantia nigra. OBJECTIVE： To investigate the effects of TSPG on human embryonic neural stem cells （NSCs） proliferation and differentiation into dopaminergic neurons using in vitro studies, and to observe NSC differentiation in a mouse model of Parkinson＇s disease, as well as behavioral changes before and after transplantation. DESIGN, TIME AND SETTING： In vitro neural cell biology trial and in vivo randomized, controlled animal trial were performed at the Institute of Basic Medical Sciences, Chongqing Medical University between September 2004 and December 2007. MATERIALS： TSPG （purity 〉 95%） was isolated, extracted, and identified by Chongqing Academy of Chinese Materia Medica. Recombinant human basic fibroblast growth factor （bFGF） and recombinant human epidermal growth factor （EGF） were purchased from PeproTech, USA. A total of 25 C57/BL6J mice, aged 18-20 weeks were included. Twenty were used to establish a Parkinson＇s disease model with i.p. injection of MPTP （1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine） and TSPG alone or combined with interleukin-1 （IL-1）-treated NSCs prior to transplantation into the corpus striatum. The remaining five mice were pretreated for 3 days with TSPG prior to MPTP injection, serving as the TSPG prevention group. METHODS： Primary NSCs were isolated, cultured and purified from embryonic cerebral cortex. Immunocytochemistry was employed to detect specific antigen expression in the NSCs. In vitro experiment： （1） to induce proliferation, NSCs were treated with TSPG, EGF＋bFGF, or TSPG＋EGF＋bFGF, respectively; （2） to induce dopaminergic neuronal differentiation, NSCs were treated with TSPG, IL-1, or TSPG＋IL-1, respectively. MAIN OUTCOME MEASURES： In vitro experiment： the effects of TSPG on NSCs proliferation were evaluated with flow cytometry and MTT assay. Tyrosine hydroxylase expression was determined by immunocytochemistry assay to observe effects of TSPG on dopaminergic neuronal differentiation. In vivo experiment： differentiation of grafted NSCs in the mouse brain was determined by immunohistochemical staining. Behavioral changes were evaluated by spontaneous activity frequency, memory function, and score of paralysis agitans. RESULTS： （1） NSCs were cultured and passaged for more than three passages. Immunocytochemistry revealed positive nestin staining, as well as neurofilament protein and glial fibrillary acidic protein. （2） TSPG significantly increased NSC proliferation, in particular when combined with EGF and bFGF, which was twice as effective as FGF or bFGF alone. TSPG also induced dopaminergic differentiation in NSCs, in particular when TSPG was added together with IL-1, resulting in an effect five times greater than that of IL-1 alone. （3） At day 30 following transplantation, most NSCs in the TSPG prevention group differentiated into dopaminergic neurons, and the scores of paralysis agitans, spontaneous activity, and memory function were significantly increased compared with TSPG alone or TSPG＋IL-1 groups （P 〈 0.05）. CONCLUSION： TSPG stimulated NSC proliferation, in particular when combined with FGF and bFGF. TSPG significantly induced dopaminergic neuronal differentiation of NSCs, and the effect was greater when combined with IL-1. In addition, TSPG greatly improved behavior in the Parkinson＇s disease mouse model following NSC transplantation. Following NSC transplantation, TSPG pretreatment exhibited superior efficacy over either TSPG alone or TSPG in combination with IL-1, in terms of behavioral improvements in the Parkinson＇s disease mouse model.     

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.     

Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer＇s disease

Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.     

墨蝶呤还原酶基因与精神分裂症相关性的研究进展

墨蝶呤还原酶（SPR）催化四氢生物蝶呤（BH4）从头合成途径的最后一步反应。SPR基因遗传缺陷或突变可导致BH。的合成紊乱,影响单胺类神经递质（如多巴胺、5-羟色胺及谷氨酸等）的合成或释放,进而参与包括精神分裂症在内的多种神经精神系统疾病的发生发展过程。此外,SPR基因敲除小鼠表现出持续增强的自主活动等类精神分裂症症状,说明该基因在精神分裂症的发病中扮演重要的角色。进一步研究SPR基因及其单核苷酸多态性的功能,可为阐明精神分裂症的发病机制提供重要的线索,也为新一代抗精神病药物的研制及开发开拓新的视野。现对SPR基因与精神分裂症的相关研究做一综述。     

Wnt信号通路与骨髓间充质干细胞增殖及分化的关系

骨髓间充质干细胞（bonemarrow—derived mesenchymal stem cells,BMSCs）是骨髓中不同于造血干细胞的一类细胞,其来源丰富,取材简便,易分离、纯化、培养,在一定的条件下可以迅速体外扩增,具有多向分化潜能,可以通过不同的方法被诱导分化成骨细胞、软骨细胞、肌细胞、神经胶质细胞、神经元细胞等,而且它具有低免疫源性,向病变部位迁移的能力,     

癫痫与自杀

自杀而导致死亡被为是增加癫痫患者死亡率的最重要原因之一。国外许多研究报道都表明癫痫患者的自杀率比普通人群的自杀率高几倍到二十几倍。可能导致癫痫患者自杀的危险性因素是有多方面的,本文将从5-HT、抗癫痫药及癫痫手术治疗、精神病理等方面对癫痫患者可能存在自杀危险因素进行综述,并希望在癫痫的综合治疗中对这些危险因素能加以考虑。