KIF5A基因突变致家族性肌萎缩侧索硬化一例

<正>1 病例报告患者(即先证者)女,40岁,家庭主妇,因“进行性四肢无力3个月”于2022-11-14就诊于南京医科大学附属脑科医院老年神经科。患者于此次就诊3个月前无明显诱因出现右上肢近端力弱,未重视,症状逐渐加重,日常活动基本不影响;1个月前患者自觉右上肢无力加重,表现为右上肢不能平举、右手不能持物紧握,同时患者自感左上肢抬起费力,持物尚未受到影响,并逐渐出现双下肢近端力弱,蹲下站起费力。患者于外院就诊,     

四肢无力3月余 视物成双2 个月 尿急1 个月简

病历摘要 患者女性,55岁。因四肢无力3月余、视物成双2个月,加重伴尿急1个月,于2013年10月31日入院。患者入院前3个月（2013年7月中旬）出现双下肢肌力减弱、行走易疲劳,尤以上台阶费力,但下蹲后可自行站起,晨起、休息后症状缓解,晚间或活动后症状加重;约2周后（2013年7月底）出现双上肢肌力减弱,抬手臂或梳头无力,能持握碗筷,不伴肢体麻木、肌柬颤等,至当地医院就诊。     

第53例--右侧肢体无力伴口渴、多饮、多尿

患者，男，22岁。住院13个月前（2002年10月)曾有感冒发热病史．住院12个月前(2002年11月)出现右面部发胀．右眼部发紧感，右手1，2、3手指麻木，住院9个月前(2003年2月)出现右手发抖．写字不流利．烦躁．话少．并逐渐出现右下肢行走费力．头颅CT未见异常。     

莫旺综合征1例报告

<正>莫旺综合征是一种少见的与电压门控钾离子通道(VGKC)复合物抗体相关的自身免疫性疾病,现报告1例病例如下。1 病例患者男性,61岁,因"肌肉跳动、无力2月余,加重伴躁动不安二十余天"于2016年9月5日收入我院。患者于2个月前无明显诱因出现全身肉跳,呈持续性,伴大小便费力,否认肢体僵硬、痛性痉挛。发病1个月后患者出现四肢无力,坐起费力,需拄拐行走,伴下肢皮肤瘙痒感。发病2个月后出现顽固性失眠,夜间出现错觉、烦躁、答非所问,虚构不     

单纯呼吸肌麻痹型吉兰-巴雷综合征一例报告

患者,女性,３２岁。因气促、胸闷１个月,呼吸骤停１周而于１９９８年７月２２日入院。患者于４０天前曾作过剖腹产术,术后第１０天出现气促、呼吸费力、胸闷、心悸。心电图、肝肾功能、胸片、心超检查等均无异常发现。但上述症状逐渐加重。１周前出现口唇发绀、意识丧...     

双侧小脑中脚对称性病灶的多系统萎缩一例

患者男性．44岁，因尿便障碍1年，头昏6个月，行走不稳3个月入院。入院前1年无明显诱因逐渐出现小便费力，解不尽，后逐渐出现便秘及阳痿。入院前半年起多次出现短时跑步后及由床上突然起立出现黑噱，静坐及平卧后可缓解，伴进食、饮水呛咳及语调不稳。入院前3个月起行走不稳，方向不定，时有跌跤。上述症状逐渐加重。既往体健，     

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。     

一例巨长胸椎管内血管脂肪瘤报道

患者女,24岁,主因“双下肢无力7年,加重3个月”于2013年8月25日人院。患者7年前出现双下肢无力,并进行性加重,半年后双下肢瘫痪伴感觉障碍,就诊多家当地医院,行胸椎核磁提示椎管内占位（T1-11）,因手术困难,未行手术治疗,后服中药治疗（具体不详）,症状逐渐缓解至正常。3个月前患者再次出现双下肢无力,自述乳头水平以下无感觉,症状进行性加重,1个月前患者无法行走,伴乳头水平以下感觉减退,以右侧显著,为进一步治疗收住院。     

丙戊酸钠对成人癫痫患者认知功能的影响

目的了解丙戊酸钠对成人癫痫患者认知功能的影响。方法采用简易精神状态评定量表,分别于治疗前及治疗6个月、1年、2年、3年对74例接受丙戊酸钠治疗的成人癫痫患者认知功能进行评价,并选同期健康体检者85例作为对照组。结果癫痫组丙戊酸钠血药浓度均在正常浓度范围。简易精神状态评定量表评分：在干预前,癫痫组11项得分均低于对照组（P〈0.01）;在干预后6个月、1年、2年、3年,癫痫组11项得分均低于对照组（P〈0.05）;癫痫组自身与治疗前比较,11项得分均增高（P〈0.05）,但随时间延长无进一步改善趋势（P〉0.05）;癫痫组治疗前后原发性和继发性癫痫患者间比较无差异（P〉0.05）。结论成人癫痫患者存在认知功能下降,丙戊酸钠具有改善癫痫患者认知功能的作用。     

抗MuSK抗体阳性的重症肌无力合并Graves病一例

正患者男性,24岁,因视物成双伴双眼上睑下垂22个月、加重6周,于2017年7月7日至河北省保定市第一中心医院就诊。22个月前(2015年9月)无明显诱因出现视物成双,自觉左眼不能外展,习惯性单眼视物,继而出现双眼上睑下垂,眼睑抬举费力,伴多汗、皮肤潮湿和手抖,无视力下降、视野缺损,无头痛、言语不清、张口困难、颈肌无力、肢体     

硬脊膜动静脉瘘的早期诊断策略

目的硬脊膜动静脉瘘（SDAVF）是一种缓慢进展的脊髓血管性疾病,临床表现无特殊性,容易误诊。现分析3例得到早期诊断病例的资料,以期制定SDAVF早期诊断的策略。方法对近年来得到早期诊断的3例SDAVF患者诊断资料进行分析,总结其临床表现特征、诊断程序及内容。结果3例SDAVF患者均表现为双下肢无力或麻木,运动后加重等特点。磁共振检查出现脊髓周边血管流空影及局部脊髓水肿均高度提示SDAVF,均通过DSA获得确诊。结论对于临床表现疑似SDAVF患者,脊髓MRI扫描和进一步的DSA检查有助于早期诊断,提高治疗效果。     

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.     

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。     

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.