重症肌无力患者胸腺切除术后合并视神经脊髓炎1例（附文献复习）

目的：分析重症肌无力（MG）患者胸腺切除后合并视神经脊髓炎的临床特点,探讨两者合并发生的机制。方法：结合文献对1例MG胸腺切除后合并视神经脊髓炎患者的临床特点和血清学改变进行分析。结果：现有的MG合并视神经脊髓炎的文献报道中,绝大多数（13/15例）在胸腺切除后发生。胸腺切除后抑制T细胞产生减少,B细胞过度增殖,自身免疫抗体增加,可能与视神经脊髓炎的发病有关。此外,HLAB8、DR2和DR3也可能与MG合并视神经脊髓炎的发生相关。结论：MG患者胸腺切除后引起的免疫系统改变（如血清中抑制T细胞数的改变和自身抗体的出现）,患者的HLA抗原类型（如HLA-B8、DR2和DR3）可能与合并视神经脊髓炎的发生相关。     

视神经脊髓炎——是否是多发性硬化的一个亚型？

目的 探讨视神经脊髓炎与多发性硬化的方法。方法 对１３例视神经脊髓炎患者的临床表现,脑脊液,电生理学及影像学检查结果进行分析。结果 ８５％的视神经脊髓炎患者有多次（平均３．１次）的缓解复发,复发时症状仅限于视神经和／或脊髓,其脑脊液中寡克隆区带阳性率３３％,脑干诱发电位异常率８％,头颅ＣＴ和ＭＲＩ未发现异常。结论 视神经脊髓炎和多发性硬化之间有所不同,支持视神经脊髓炎是一个单独的疾病单元学说。     

视神经脊髓炎的临床及磁共振成像研究

目的探讨视神经脊髓炎临床与MRI表现特点。方法回顾分析20例经临床或实验室检查明确诊断的视神经脊髓炎患者临床资料,总结其发病特点。结果视神经脊髓炎多以急性脊髓炎（13例）或视神经炎（7例）为首发症状,复发病程（18例）多见。临床主要表现为急性视力减退、视野呈向心性缩小或复视（7例）,以及病灶平面以下运动、感觉和自主神经功能紊乱（13例）。部分患者眼底呈急性视神经炎、视乳头水肿（3例）,球后视神经炎（5例）或视神经萎缩（4例）变化;视觉诱发电位呈现潜伏期延长、波幅下降和波形分化不良（7例）。脑脊液和血清免疫球蛋白IgG阳性检出率分别为44．44％（8／18）和50．00％（6／12）,寡克隆区带阳性率为27．78％（5／18）。8例患者头部MRI检查显示存在颅内病灶,分布于下丘脑、脑桥、中脑、第四脑室周围。结论实验室检查有助于视神经脊髓炎的诊断与鉴别诊断,第三、第四脑室周围和脑桥等病灶分布具有特征性,与脑内水通道蛋白4高表达区域相一致。     

视神经脊髓炎36例临床分析（附24例MRI检查）

视神经脊髓炎３６例临床分析（附２４例ＭＲＩ检查）刘德新视神经脊髓炎（又称Ｄｅｖｉｃ综合征）。临床表现以急性或亚急性视神经和脊髓损害为特征。近年来认为视神经脊髓炎是多发性硬化的一种变异型。本文收集３６例视神经脊髓炎，对其中２４例进行了随访观察４～８年，...     

神经系统副肿瘤综合征16例临床分析

目的　对神经系统副肿瘤综合征的临床特点进行分析，探讨可能的病因。方法　对１６ 例神经系统副肿瘤综合征患者临床资料进行回顾性分析。结果　本组临床类型有：肌无力综合征（１０ 例） ，周围神经病（７ 例） ，脑脊髓炎（４ 例） ，亚急性小脑变性（２ 例） ，其中肌无力综合征合并周围神经病４ 例，肌无力综合征合并脑脊髓炎２ 例，肌无力综合征合并周围神经病、脑脊髓炎１ 例；肌无力综合征合并周围神经病、亚急性小脑变性１ 例。肿瘤类型有小细胞未分化肺癌、腺癌、淋巴瘤等。结论　神经系统副肿瘤综合征临床表现形式多样，免疫机制异常可能在发病中起重要作用。     

74例重症肌无力危象的临床分析

目的 探讨重症肌无力危象患者的临床特点和预后。方法 回顾74 例第一次发生肌无 力危象的重症肌无力患者的一般资料，分析Osserman 分型、危象发生时间、危象前特点、危象持续时间， 评价重症肌无力危象治疗效果及预后。结果 伴胸腺瘤的重症肌无力危象患者45 例，占60.81%，非胸 腺瘤患者29 例，占39.19%。60.81%（45/74）的肌无力危象发生在重症肌无力起病的1 年之内，胸腺切除 术后6 个月内发生危象的比例为76.00%（38/50）。呼吸费力和吞咽费力（24/74）是出现危象前最显著的特 征，其次为胸腺手术后（11/74）、感染（9/74）、激素相关（7/74）。所有危象患者中Osserman 分型ⅡB 型所占 比例最高，为45.95%（34/74）。重症肌无力危象患者的插管时间为15（7，30）d，44.60%（33/74）的危象患者 需要丙种免疫球蛋白和（或）血浆置换联合甲泼尼龙冲击治疗。肌无力危象最常见的并发症为肺部感染 （32/74，43.24%），反复气管插管最严重的并发症为支气管扩张伴出血、气胸。随访2～10 年，17 例患者 出现再次或多次危象，死亡率为9.46%（7/74）。结论 伴胸腺瘤的重症肌无力患者较不伴胸腺瘤患者出 现肌无力危象的比例更高。重症肌无力危象治疗困难，需要多种免疫抑制剂联合治疗。胸腺切除后的 半年内，仍然是肌无力危象发生的高峰。肌无力危象并发症、反复危象、胸腺瘤转移是患者死亡的主要 原因。     

视神经炎与多发性硬化的视神经功能障碍

目的：探讨视神经炎与多发性硬化（MS）视神经功能改变的特点,方法：采用x^2检验与t检验对患者视神经功能改变的特点进行分析。结果：（1）视神经炎视力障碍严重,82％视力低于0．1,MS视功能障碍常见,其中尤以MS视神经脊髓炎型严重,81％视力低于0．1,77％双眼视力低于0．1。（2）视神经炎,MS的VEP异常率高达80－88％,MS视神经脊髓炎型VEP异常率高达95％,主要表现为潜伏期延长,（3）视神经炎鞘内IgG合成率低于MS。（4）两组部分患者经过大剂量肾上腺糖皮质激素治疗后,视力恢复到0．5以上者约31％－33％。结论：视神经炎是MS的最常见症状之一,视神经炎与MS视神经脊髓炎型的视神经损害发生频率高且程度重,迫切需要对急性视神经炎患者进行早期诊断并及时给予大剂理肾上腺糖皮质激素治疗。     

重症肌无力患者血清干扰素-α抗体的检测意义

目的研究重症肌无力（MG）患者外周血中干扰素α抗体（IFN-αAb）的含量,并探讨其与MG的关系。方法采用ELISA法测定60例MG患者、20例正常对照组（NC）及20例非MG其他神经系统疾病患者（OND）血清中IFN-αAb。结果 发现伴胸腺瘤的重症肌无力患者（MGT）血清中IFN-αAb阳性率为75%,明显高于不伴胸腺瘤的重症肌无力患者（NTMG,11.5%）及对照组（P〈0.05）;晚发型MG者IFN-αAb阳性率为29.41%,明显高于早发型MG患者7.69%（P〈0.05）。结论 伴胸腺瘤的MG患者及晚发型MG患者外周血中IFN-αAb表达增高。     

重症肌无力与人类嗜T淋巴细胞I型病毒抗原的关系

采用免疫荧光法检测２５例重症肌无力患者外周血细胞中人类嗜Ｔ淋巴细胞Ｉ型病毒（ＨＴＬＶ－１）抗原。结果显示，２０％（５／２５）的重症肌无力患者血细胞中ＨＴＬＶＩ抗原阳性，而对照组７１例全部为阴性。两组比较差异有极显著性意义。提示重症肌无力的发病可能与ＨＴＬＶ－１的感染有关。     

重症肌无力与人类嗜T淋巴细胞：I型病毒抗原的关系

采用免疫荧光法检测２５例重症肌无力患者外周血细胞中人类嗜Ｔ淋巴细胞Ｉ型病毒（ＨＴＬＶ－１）抗原。结果显示，２０％（５／２５）的重症肌无力患者血细胞中ＨＴＬＶ－１抗原阳性，而对照组７１例全部为阴性。两组比较差异有极显著性意义。提示重症肌无力的发病可能与ＨＴＬＶ－１的感染有关。     

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.     

高血压脑出血的显微外科治疗进展

高血压脑出血（Hypertensive intrac-rebral hemorrhage,HICH）是具有高发病率、高病死率、高致残率的急性脑血管疾病,占所有脑卒中患者的10%-20%,早期病死率可高达49.4%。随着人口老龄化,其发病率逐年提高;而外科手术的干预,使其病死率有所下降,但致残率居高不下。如何提高手术疗效和患者生存质量,一直是神经外科医师努力的方向。微侵袭血肿清除术因其手术创伤小,恢复快,是目前国内治疗高血压脑出血的重要手段。     

神经内镜联合亚低温治疗高血压基底节区脑出血

目的 探讨神经内镜联合亚低温在治疗高血压基底节区脑出血中的临床应用价值.方法 回顾性分析我院神经内镜治疗高血压基底节区脑出血患者40例的临床资料,并对治疗结果进行分析.结果 神经内镜治疗组22例(甲组),神经内镜联合亚低温治疗组18例(乙组),术后3个月根据GCS评分,甲组恢复良好1例,中残4例,重残6例,植物生存6例,死亡5例;乙组恢复良好4例,中残8例,重残3例,植物生存1例,死亡2例,两组比较差异有统计学意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组颅内压明显降低.结论 神经内镜是治疗高血压基底节区脑出血较为有效的手术方式,联合亚低温治疗能有效降低颅内压,改善术后神经功能恢复,具有较好的临床应用价值.     

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.     

Dysfunctional autophagy in Alzheimer＇s disease： pathogenic roles and therapeutic implications

Neuronal autophagy is essential for neuronal survival and the maintenance of neuronal homeostasis. Increasing evidence has implicated autophagic dysfunction in the pathogenesis of Alzheimer＇s disease （AD）. The mechanisms underlying autophagic failure in AD involve several steps, from autophagosome formation to degradation. The effect of modulating autophagy is context-dependent. Stimulation of autophagy is not always beneficial. During the implementation of therapies that modulate autophagy, the nature of the autophagic defect, the timing of intervention, and the optimal level and duration of modulation should be fully considered.     

Oxidative stress in Alzheimer＇s disease

Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.     

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.     

Effects of p75 neurotrophin receptor knockout on axonal regeneration in a mouse model of facial nerve injury

BACKGROUND： Previous studies have shown that p75 neurotrophin receptor plays an important role in peripheral nerve injury. However, the role of p75 neurotrophin receptor in the regeneration of peripheral nerves remains poorly understood. OBJECTIVE： To study the effect of p75 neurotrophin receptor on facial nerve regeneration. DESIGN, TIME AND SETTING： A randomized controlled experiment was performed in the Regeneration Laboratory of Flinders University, Australia and the Biomedical Laboratory of Dentistry School, Shandong University from March 2005 to February 2006. MATERIALS： Cholera toxin B subunit, fast blue, and biotin rabbit-anti goat IgG were provided by Sigma, USA; goat-anti choleratoxin B subunit ant/body was provided by List Biologicals, USA. METHODS： In p75 neurotrophin receptor knockout and wild type 129/sv mice, the facial nerves on one side were crushed. At days 2 and 4 following injury, regenerating motor neurons in the facial nuclei were labeled by fast blue, and the regenerating axon was labeled by the anterograde tracer choleratoxin B subunit. MAIN OUTCOME MEASURES： Axonal regenerative velocity and number were detected by immunohistochemical staining of choleratoxin B subunit, growth-associated protein, protein gene product 9.5, and calcitonin-gene-related peptide; survival of motor neurons in the facial nuclei was detected by retrograde fast blue. RESULTS： Axonal growth in the facial nerve of p75 neurotrophin receptor knockout mice was significantly less than in wild type mice. At day 7 after injury, the number of regenerating motor neurons in p75 neurotrophin receptor knockout mice remained significantly less than in wild type mice （P 〈 0.05）. The number of positively stained fibers for growth-associated protein-43, protein gene product 9.5, and calcitonin-gene-related peptide in p75 neurotrophin receptor knockout mice was significantly less than in wild type mice （P 〈 0.01）. CONCLUSION： p75 neurotrophin receptor promoted axonal regeneration and enhanced the survival rate of motor neurons following facial nerve injury.     

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.