31例成人中枢神经系统白血病临床分析

目的：探讨成人非淋巴细胞白血病(ANLL)患者并发中枢神经系统白血病(CNSL)的临床特征。方法：回顾性分析3l例成人CNSL患者的临床资料。结果：3l例成人CNSL患者中，ANLL20例，分别为M2一M5患者。其中3例确诊于发病初期，l7例确诊于巩固期；40岁以下者27例，占87．0％，平均年龄27．48岁，目前死亡15例，失访2例，生存14例。结论：成人ANLL患者并发CNSL发生率高，病情危笃，预后差；临床应重视其预防治疗。     

甲状腺机能减退对仔鼠中枢神经系统Ⅱ型脱碘酶mRNA表达的影响

目的观察甲状腺激素机能减退(甲减)时仔鼠中枢神经系统Ⅱ型脱碘酶mRNA(D2-mRNA)的表达,研究甲状腺激素对脑发育调控的机制。方法怀孕Wistar雌鼠随机分为甲减组和对照组,从怀孕15d开始甲减组每日经胃灌注1%丙基硫氧嘧啶2.5ml,所生鼠即为甲减仔鼠。对照组每日经胃灌注生理盐水2.5ml。分别于出生时、出生后14、21和45d处死仔鼠,利用荧光定量PCR的方法,分析各组动物大脑皮质、小脑、脑干、海马及脊髓中D2的表达。结果甲减仔鼠大脑、脑干及脊髓中D2mRNA在出生时及出生后14d时表达量高于对照组,在21d和45d时与对照组无显著性差异;在小脑和海马中D2mRNA的表达量在出生时及出生后14、21d时都高于对照组,只有在45d时与对照组接近。结论甲减时仔鼠中枢神经系统D2表达增加,通过调节甲状腺激素水平对其生长发育起着重要作用。     

原发性中枢神经系统淋巴瘤23例临床分析

目的 探讨原发性中枢神经系统淋巴瘤(PCNSL)的诊断、合理治疗方案和预后的相关因素.方法 收集天津医科大学肿瘤医院2005年1月至2007年12月经病理证实且随访资料完整的23例免疫功能正常的PCNSL患者,其中男10例,女13例,中位年龄50岁.行腰穿检查者18例,检查出瘤细胞者4例.8例行开颅手术切除,15例行立体定向活检术.4例行全颅放疗,6例行以大剂量甲氨蝶呤为基础的联合化疗,13例行放疗联合化疗.分析其治疗、临床特点与预后之间的联系.结果 Kaplan-Meier分析显示本系列患者中位生存期45.0个月,3年生存率56.5％.Log-Rank检验发现放疗联合化疗组(43.8和30.0个月)与化疗组(39.7和29.7个月)的总生存期及肿瘤无进展生存期明显长于单纯放疗组(25.7和19.8个月,P值均＜0.05);放疗联合化疗组的总生存期长于单纯化疗组(P＜0.05),2组间肿瘤无进展生存期无明显差异(P＞0.05).结论 病理诊断仍是确诊的金标准,脑脊液检查发现瘤细胞者也可确诊.以全颅放疗联合化疗为主的综合治疗优于单纯放疗或化疗.     

Vascular involvement of the central nervous system and systemic diseases: etiologies and MRI findings

The objective of this study was to review magnetic resonance imaging (MRI) findings in patients with vascular involvement of the central nervous system (CNS) associated with systemic diseases. We reviewed the MRI findings in clinically suspected cases of vascular involvement of the CNS associated with systemic diseases. Vascular CNS involvement was considered in the presence of characteristic clinical, MRI and/or MR angiography findings. In order to be included in the study, patients needed to have a complete clinical and laboratory investigation and a follow-up of a minimum of 6 months. Twenty-four patients (17 women and 7 men), with mean age of 29.5 years had diagnosis of CNS vasculitis and were included. The clinical presentation was variable, but the most common complaints were headache in 18, focal deficits in 9, disturbances of consciousness in 9, and seizures in 8 patients. Underlying causes for CNS vasculitis were identified in all patients and included systemic lupus erythematosus in eight, tuberculosis in three, bacterial meningitis in three, Takayasu arteritis in two, polyarteritis nodosa in two, syphilis in two, drug abuse in two, yellow fever in one and varicella in one patient. Nonspecific high intensity T2WI/FLAIR lesions in white matter were the most common finding, present in ten patients. Eight patients had infarctions in large cerebral arteries territory, associated or not with high intensity T2WI/FLAIR small foci. Vascular involvement of the CNS can be found in a great variety of systemic diseases, including rheumatologic, infectious and drug abuse. Clinical findings are unspecific and MRI/MRA may help to establish the correct diagnosis.     

Retrospective study of prognostic factors in non-Hodgkin lymphoma secondarily involving the central nervous system

The aim of this retrospective single-center study was to analyze the clinical characteristics and outcome of non-Hodgkin lymphoma (NHL) patients with central nervous system (CNS) involvement and to identify prognostic factors for survival. We searched our hospital records for NHL patients diagnosed with CNS involvement from 1982 to 2004, and 43 patients were identified. The median age was 63 years (range 23–88) and the median Karnofsky performance status was 55% (range 10–90). Treatment of CNS lymphoma included intrathecal chemotherapy in 33 patients (77%), systemic chemotherapy in 25 (58%), and radiotherapy in 16 (37%). Twenty-six patients showed a CNS response. The median survival after CNS manifestation was 5 months (range 2 days–82.5+months). Nine patients achieved long-term survival. Low lactate dehydrogenase (LDH) at CNS manifestation and a CNS response to therapy were favorable independent prognostic factors for survival in multivariate analysis (p=0.051 and p<0.0005, respectively), whereas a young age at initial diagnosis, initial CNS involvement, an initially normal LDH, and high-dose chemotherapy for CNS involvement were significant in univariate analysis. In conclusion, long-term survival can be achieved in patients with secondary CNS lymphoma. LDH at CNS manifestation and a CNS response to therapy were significantly associated with survival.     

Clinical features,prognostic and risk factors of central nervous system infections in patients with systemic lupus erythematosus

The purpose of this study is to describe the etiology, characteristics and outcomes of central nervous system (CNS) infections in patients with systemic lupus erythematosus (SLE), while also identifying prognostic and risk factors. Thirty-eight SLE patients with CNS infections were identified from review of all charts of patients with SLE hospitalized from January 1995 to June 2005. These patients were divided into 3 groups, i.e., Mycobacterium tuberculosis (TB), non-TB bacterial and fungal infection groups. Of the 38 SLE cases with CNS infections, TB was identified in 19 patients, Listeria monocytogenes in 3 patients, Klebsiella pneumoniae in 1 patient, Staphylococcus aureus in 1 patient, Gram’s stain positive bacteria in 1 patient, Cryptococcus neoformans in 12 patients, and Aspergillus fumigatus in 1 patient. The rate of unfavorable outcome in patients with fungal infection was lower than in patients with TB (P=0.028) and non-TB bacterial CNS infections (P=0.046). SLE patients with TB or fungal CNS infections had a more insidious or atypical clinical presentation. Compared to SLE patients without CNS infections, those with CNS infections were more likely to have low serum albumin levels (P=0.048) and have been receiving higher doses of prednisolone at the onset of CNS infection (P=0.015) or higher mean doses of prednisolone within the previous year (P=0.039). In conclusion, low levels of serum albumin and higher doses of received prednisolone are important risk factors for the development of CNS infections in SLE patients. This work was supported by a research grant from Shanghai Leading Academic Discipline Project, Project number: T0203 and a research grant 30371332 from National Natural Science Foundation of China (NSFC).     

小胶质细胞Toll样受体4信号转导通路与中枢神经系统损伤

中枢神经系统损伤机制复杂,小胶质细胞参与了多种中枢神经系统疾病和损伤过程.Toll样受体4(Toll-like receptor 4,TLR4)可介导小胶质细胞的活化和炎性细胞因子的表达,是小胶质细胞发挥功能的重要受体蛋白之一.文章简要介绍了小胶质细胞TLR4信号通路在中枢神经系统损伤中的作用.     

高血压对主动脉夹层患者术后早期中枢神经系统功能的影响

目的分析高血压对主动脉夹层患者术后早期中枢神经系统功能的影响。方法选取南京鼓楼医院2008-11-2011-05主动脉夹层术后患者(n=77),根据是否有中枢神经系统损伤分为损伤组(n=35)和对照组(n=42),应用单因素和多因素Logistic回归分析高血压对主动脉夹层患者术后早期中枢神经系统功能的影响。结果与对照组比较,损伤组高血压患者的比率[80%(28/35)比45%(19/42),P<0.05]、术中失血量[(5037.1±3888.1)比(2466.7±2194.2)mL,P<0.01]升高,术后24h内尿量[(1092.9±727.2)比(1399.3±510.5)mL]、术后回重症加强护理病房(ICU)第一次血气分析pH值[(7.39±0.10)比(7.44±0.08)]、术后回ICU第一次血气分析的动脉血氧分压(PaO2)值[(81.8±30.7)比(116.1±56.9)mmHg,均P<0.05]降低。单因素分析表明高血压史、术中失血量、术后24h内尿量、术后回ICU第一次血气分析的pH值、术后回ICU第一次血气分析的PaO2值可明显影响中枢神经系统功能的恢复;多因素分析表明高血压史(OR0.196)及术后回ICU第一次血气分析PaO2值(OR1.015)是影响中枢神经系统功能恢复的独立危险因素。结论高血压是影响主动脉夹层患者术后早期中枢神经系统功能恢复的独立危险因素。     

艾滋病合并中枢神经系统病变61例分析

目的提高艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人合并中枢神经系统病变的确诊率,了解治疗方法及提高疗效,改善预后。方法统计61例HIV/AIDS合并中枢神经系统病变的病人,分析CD4细胞计数、脑脊液常规、生化、免疫学、病原学、头颅计算机层析成像(CT)或核磁共振成像(MRI)及脑活检等检查,了解诊断情况、治疗及预后。结果 632例HIV/AIDS病人中,合并中枢神经系统症状者61例,发病率9.7%。病人伴有不同程度的发热、头痛、恶心呕吐、意识障碍、抽搐、肢体痛温觉障碍、活动障碍、智力下降、痴呆、脑膜刺激征、定位体征等临床表现。诊断为:隐球菌脑膜炎25例(41.0%),不明原因的中枢神经系统感染11例(18%),进行性多灶性脑白质病(PML)8例(13.1%),不明原因占位6例(9.8%),艾滋病脑病5例(8.2%),弓形体脑病4例(6.6%),结核性脑膜炎3例(4.9%),脑梗死2例(3.3%)。其中PML合并隐球菌脑膜炎、弓形体脑病、艾滋病脑病各1例。好转27例,死亡11例,未愈自动出院23例。CD4计数50个/mm336例,200个/mm34例。有明确的病原学依据的27例,脑活检病理确诊者1例,其余均为临床诊断。结论 HIV/AIDS病人易合并各种中枢神经系统并发症,诊断困难,死亡率高。对于AIDS病人,尤其CD4计数200个/mm3的病人,如出现以上症状,应及时行脑脊液及头颅影像学检查,必要时应行脑活检,尽可能得到病原学及病理支持,以提高确诊率,及时进行相应治疗,改善预后。     

造血干细胞移植后中枢神经系统并发症的临床研究

目的 探讨造血干细胞移植(HSCT)后中枢神经系统(CNS)并发症的发生率影响因素及预后,提高CNS并发症的诊断和治疗水平,从而改善此类患者的生存.方法 研究对象为自2001年5月至2007年12月在北京市道培医院行HSCT的640例患者,对其中发生CNS并发症患者的临床特点进行回顾性分析和研究.结果 640例HSCT患者中共57例发生了CNS并发症,发生率为8.9%.非血缘、单倍型和间胞相合HSCT后CNS并发症的发生率分别为12.0%(10/83),13.5%(39/289)和3.4%(8/237)(P<0.001).预处理为全身照射(TBI)和非TBI方案的发生率分别为19.4%(7/36)和8.3%(50/604)(P=0.047).年龄<14岁组和年龄≥14岁组的发生率分别为15.3%(9/59)和8.3%(48/581)(P=0.072).恶性疾病中的发病率为8.9%(56/627),非恶性疾病中的发病率为7.7%(1/13)(P=1.000).最常见的并发症为原发病复发和颅内感染.患者总体病死率为57.9%(33/57),其中66.7%(22/33)的患者死亡原因为CNS并发症.结论 单倍型和非血缘移植、TBI的预处理方案是移植后发生CNS并发症的高危因素.而年龄和原发病类型对CNS并发症的发病率无显著影响.早期诊断和积极有效地治疗CNS并发症可以降低其相关病死率,改善患者的预后.     

原发性中枢神经系统淋巴瘤18例临床分析

目的探讨原发性中枢神经系统淋巴瘤(PCNSL)的诊断及治疗措施。方法回顾性分析18例PCNSL的临床、影像学特征及治疗效果。结果18例患者均经手术病理确诊;15例患者行手术治疗和(或)术后放疗和(或)常规CHOP方案化疗,生存期为3~18个月;3例患者手术确诊后使用大剂量甲氨蝶呤(MTX)为主的方案化疗及鞘内注射药物等治疗,生存期均大于36个月。结论PCNSL临床症状及影像学无特征性,诊断困难,易误诊;手术治疗、术后放疗及常规CHOP方案化疗的疗效欠佳,采用易通过血脑屏障药物治疗可取得一定的疗效。     

潮汕地区中枢神经系统疾病肠道病毒感染调查

目的对潮汕地区1972年-2003年间临床诊断为中枢神经系统(CNS)疾病的1 605例患者进行肠道病毒(EV)感染调查.方法采集临床诊断为CNS疾病的患者脑脊髓液、血液、咽拭子或粪便标本共l 605份.用Hep-2细胞对标本进行病毒培养;用免疫血清微量中和试验对分离出的毒株进行鉴定;采集患者的双份血清进行中和抗体检测.结果从l 605例CNS疾病患者(包括疑似脊髓灰质炎、脑炎、格林-巴利综合征、脊髓压迫症、脑血管意外、颅内积水或占位和多发性硬化)的各种标本中共检测出4种25个型EV病原541例,EV病毒总检出率为33.7%,患者EV感染型别分布及检出率构成比分别为:脊髓灰质炎病毒(Polio)260例(0.480 6);柯萨奇病毒(Cox)169例(0.3124);埃可病毒(ECHO)57例(0.105 4);新型EV 55例(0.101 6).结论潮汕地区CNS疾病中存在EV感染.不同年份EV的检出率不尽相同,1972年-1979年、1980年-1989年、1990年-1994年这三个时间段里EV检出率以Polio最高;1995年-2003年EV检出率则以Cox最高.随着脊髓灰质炎疫苗的普及接种,1995年后未再发现Po-lio.     

系统性红斑狼疮合并中枢神经系统感染的临床特点分析

目的 分析系统性红斑狼疮(SLE)合并中枢神经系统(CNS)感染的临床特点及相关危险因素.方法 对18例诊断为SLE合并CNS感染的患者和随机抽取的36例SLE患者的临床资料进行回顾性分析.结果 CNS感染组与对照组在大剂量激素冲击(22%与3%,P<0.05),1年内日平均激素用量[(35±18)mg/d与(24±17)mg/d,P<0.05],外周血白细胞[(4.4±3.4)×109/L与(6.7±2.9)×109/L,P<0.05]、淋巴细胞计数[(0.7±0.6)×109/L与(1.5±0.7)×109/L,P<0.01]和临床转归(病死率22%与0,P<0.05)方面的差异有统计学意义.结论 SLE患者合并CNS感染的临床表现不典型.大剂量激素冲击治疗,日平均激素剂量大以及外周血白细胞、淋巴细胞减少是SLE患者发生CNS感染的危险因素.     

系统性红斑狼疮并发中枢神经系统病变的危险因素

目的 探讨系统性红斑狼疮（ＳＬＥ）并发中枢神经系统（ＣＮＳ）病变的危险因素。方法 对４６例并发ＣＮＳ病变的ＳＬＥ患者进行回顾性分析,并与１５２例无ＣＮＳ病变患者做对照。结果 ＳＬＥ的ＣＮＳ表现以癫痫最常见,占５４．３％,其次为精神异常,占３０．４％。与无ＣＮＳ病变的患者对照,两组在发病年龄和病程方面均无显著性差异（Ｐ〉０．０５）。ＳＬＥ病情重者在ＣＮＳ病变组有４３例（９３．５％）,在对照组有４１例     

Similar chemokine receptor profiles in lymphomas with central nervous system involvement – possible biomarkers for patient selection for central nervous system prophylaxis,a retrospective study

Central nervous system (CNS) relapse occurs in around 5% of diffuse large B‐cell lymphoma (DLBCL) cases. No biomarkers to identify high‐risk patients have been discovered. We evaluated the expression of lymphocyte‐guiding chemokine receptors in systemic and CNS lymphomas. Immunohistochemical staining for CXCR4, CXCR5, CCR7, CXCL12, and CXCL13 was performed on 89 tissue samples, including cases of primary central nervous system lymphoma (PCNSL), secondary CNS lymphoma (sCNSL), and systemic DLBCL. Also, 10 reactive lymph node samples were included. Immunoelectron microscopy was performed on two PCNSLs, one sCNSL, one systemic DLBCL, and one reactive lymph node samples, and staining was performed for CXCR4, CXCR5, CXCL12, and CXCL13. Chi‐square test was used to determine correlations between clinical parameters, diagnostic groups, and chemokine receptor expression. Strong nuclear CXCR4 positivity correlated with systemic DLBCL, whereas strong cytoplasmic CXCR5 positivity correlated with CNS involvement (P = 0.003 and P = 0.039). Immunoelectron microscopy revealed a nuclear CXCR4 staining in reactive lymph node, compared with cytoplasmic and membranous localization seen in CNS lymphomas. We found that CNS lymphoma presented a chemokine receptor profile different from systemic disease. Our findings give new information on the CNS tropism of DLBCL and, if confirmed, may contribute to more effective targeting of CNS prophylaxis among patients with DLBCL.     

解耦联蛋白4及其在中枢神经系统疾病中的作用

解耦联蛋白4(uncoupling protein 4,UCP4)是在大脑皮质和海马特异性表达的解耦联蛋白家族成员,可通过解耦联、降低线粒体膜电位、调节Ca2+稳态以及氧化应激等机制在帕金森病、多发性硬化、癫(癎)、脑血管病和脑外伤等中枢神经系统疾病中起着重要作用.文章综述了UCP4及其在中枢神经系统疾病中的作用,以期为开发以UCP4为治疗靶点的药物提供一定的依据.

Abstract：

Uncoupling protein 4 (UCP4) is a member of the multigenic uncoupling proteins (UCPs), specific expressing in the cerebral cortex and hippocampus. UCP4 plays an important role in Parkinson's disease, multiple sclerosis, epilepsy, stroke, brain trauma and other central nervous system diseases by uncoupling, decreasing mitochondrial membrane potential,regulating Ca2+ homeostasis and oxidative stress. This article reviews UCP4 and its roles in the central nervous system diseases in order to provide certain basis for the development of UCP4targeted medication.     

Regulation of lipid metabolism by energy availability: a role for the central nervous system

The central nervous system (CNS) is crucial in the regulation of energy homeostasis. Many neuroanatomical studies have shown that the white adipose tissue (WAT) is innervated by the sympathetic nervous system, which plays a critical role in adipocyte lipid metabolism. Therefore, there are currently numerous reports indicating that signals from the CNS control the amount of fat by modulating the storage or oxidation of fatty acids. Importantly, some CNS pathways regulate adipocyte metabolism independently of food intake, suggesting that some signals possess alternative mechanisms to regulate energy homeostasis. In this review, we mainly focus on how neuronal circuits within the hypothalamus, such as leptin‐ ghrelin‐and resistin‐responsive neurons, as well as melanocortins, neuropeptide Y, and the cannabinoid system exert their actions on lipid metabolism in peripheral tissues such as WAT, liver or muscle. Dissecting the complicated interactions between peripheral signals and neuronal circuits regulating lipid metabolism might open new avenues for the development of new therapies preventing and treating obesity and its associated cardiometabolic sequelae.     

32例AIDS伴发中枢神经系统感染病人临床分析

目的分析艾滋病(AIDS)住院病人中,中枢神经系统感染的发病率、疾病谱及临床特点。方法对2009-2011年,在北京佑安医院住院治疗的AIDS伴发中枢神经系统感染病人的临床资料进行回顾总结,对其临床表现、诊治、转归等进行分析。结果 502例AIDS住院病人中,伴发中枢神经系统感染者32例,发生率6.4%。主要症状包括头痛23例(71.9%)、发热23例(71.9%)、呕吐20例(62.5%)、脑膜刺激征12例(37.5%)、肢体活动障碍9例(28.1%)、意识障碍7例(21.9%)等。这些病人的CD4细胞中位数为31/mm3,其中,≤100/mm3者27例,占总数的84.4%。诊断包括:隐球菌脑膜脑炎13例(40.6%),弓形体脑病10例(31.3%),结核性脑膜炎5例(15.6%),真菌性脑炎3例(9.4%),巨细胞病毒(CMV)脑炎1例(3.1%)。最终,32例病人中有22例(68.8%)治愈出院,5例(15.6%)死亡,5例(15.6%)未愈出院。结论 AIDS病人中枢神经系统感染以发热、头痛、呕吐、脑膜刺激征阳性等症状体征比较多见,主要发生于CD4细胞较低的病人,且病死率高,在临床中应引起重视。     

甲氨蝶呤和地塞米松鞘内注射治疗狼疮中枢受累的临床观察

目的 初步探讨鞘内注射甲氨蝶呤（ＭＴＸ）和地塞米松（ＤＸＭ）对治疗狼疮脑病（ＣＮＳＳＬＥ）的疗效。方法 选择１０例住院病人,临床上具有精神和神经异常表现,脑脊液（ＣＳＦ）检查和头颅ＣＴ或ＭＲＩ异常表现的ＣＮＳ－ＳＬＥ,在常规剂量糖皮质激素治疗ＣＮＳ－ＳＬＥ不能缓解的情况下鞘内注射ＭＴＸ和ＤＸＭ。结果 １０例病人都得到了不同程度的缓解。结论 鞘内注射ＭＴＸ和ＤＸＭ是治疗ＣＮＳ－ＳＬＥ的一种有效的方法     

胰高血糖素样肽-1受体激动剂对中枢神经系统的作用

胰高血糖素样肽-1受体(GLP-1R)激动剂通过GLP-1R刺激胰岛素分泌并改善胰岛细胞的状态,现已成为糖尿病领域研究热点.已证实GLP-1R在中枢神经系统有广泛表达,中枢应用GLP-1R激动剂后其可发挥保护神经细胞、调节食欲、调节认知功能等一系列作用,体现了其在中枢神经系统应用的潜质与价值.