多发性硬化、临床孤立综合征患者脑脊液β-淀粉样肽水平及其意义研究

目的 探讨多发性硬化(MS)及其早期表现-临床孤立综合征(CIS)患者脑脊液β-淀粉样肽(Aβ42)表达水平及其与病程、神经功能缺失以及MRI T2高信号病灶数量的关系.方法 对33例MS患者、23例CIS患者及13例对照者进行研究,MS、CIS患者发作期进行扩展残疾状态量表(EDSS)评分及MRI检查,采用液相芯片分析技术检测各组患者脑脊液Aβ42浓度.结果 MS、CIS患者发作期脑脊液Aβ42浓度与对照组相比差异无统计学意义(P>0.05),但继发进展型MS(SPMS)患者脑脊液Aβ42浓度[(167.99±36.39)pg/mL]比复发缓解型MS(RRMS)患者[(92.74±13.64)pg/mL]高,差异有统计学意义(P=0.042).MS、CIS患者脑脊液Aβ42浓度与病程及EDSS评分无明显相关性(P>0.05).病程≥1年的MS患者脑脊液Aβ42浓度比病程<1年的患者低,EDSS评分≥4.5分的MS、CIS患者脑脊液Aβ42浓度比EDSS评分<4.5分的患者低,但差异均无统计学意义(P>0.05).MS、CIS患者脑脊液Aβ42浓度与MRI T2高信号病灶数量呈正相关关系(MS患者:r=0.507.P=0.038;CIS患者:r=0.485,P=0.049).MRI T2高信号病灶总数≥4个的MS患者脑脊液Aβ42浓度[(129.34±19.96)pg/mL]比病灶总数<4个的MS患者[(73.51±12.60)pg/mL]高,差异有统计学意义(P=0.049).结论 SPMS患者轴突损伤比RRMS患者严重;脑脊液Aβ42水平升高可能是MS病情进展的标记之一;MRI T2高信号病灶负荷可能与MS轴突损伤有关.     

多发性硬化患者血清尿酸水平变化及与致残状况相关性研究

目的 探讨多发性硬化(MS)患者血清尿酸水平变化及其与致残状况的相关性.方法 收集复发缓解型多发性硬化患者42例,作为MS组,将MS组患者根据不同发作时期再分为MS-复发组和MS-缓解组；收集健康体检者42例作为对照组；比较MS与对照组间以及MS-复发组与MS-缓解组间血清尿酸水平,EDSS量表评价所有MS患者致残状况,对MS患者血清尿酸水平与EDSS评分进行相关性分析.结果 MS组血清尿酸浓度为(205.19±42.99) μmol/L,显著低于正常对照人群的(301.81±87.98) μmol/L,两组间比较差异有统计学意义(t=2.143,P＜0.05)；MS组EDSS评分为(3.9±1.1)分,较正常人群表现出显著的功能障碍；MS-复发组血清尿酸浓度为(171.47±38.33)μmol/L,显著低于MS-缓解组的(238.91±47.64) μmol/L,两组间比较差异有统计学意义(t=1.917,P＜0.05)；MS患者血清尿酸水平与其EDSS评分呈显著负相关(r=-0.365,P=0.011).结论 机体内尿酸水平的缺失在某种程度上可以影响多发性硬化的发生与进展,还与MS患者功能残障的发生及发展密切相关.     

中重度阿尔茨海默病与血管性痴呆患者脑脊液tau蛋白的预研究（英文）

背景:阿尔茨海默病(Alzheimer’s disease,AD)患病率高、医疗费用高、照料困难,已成为老龄化社会面临的严重社会、经济问题。迄今,AD的诊断尚无可靠的客观诊断指标。近年来,国内外对AD患者脑脊液生物学标志物的研究甚多,AD患者脑脊液T-tau、P-tau升高已是不争的事实。但是,这些标志物与痴呆严重程度以及随病程进展的关系还有待进一步深入研究。目标:比较中重度阿尔茨海默病(Alzheimer’s disease,AD)与血管性痴呆(vascular dementia,VD)患者脑脊液(cerebrospinal fluid,CSF)总tau蛋白(total tau,T-tau)和第231位苏氨酸磷酸化tau蛋白(P-tau231)的基线浓度,随访6个月,观察它们在AD患者与对照组之间的差异以及随病程进展的变化。方法:基线期中度AD患者11例(10≤MMSE≤20),重度AD患者10例(MMSE≤9)以及年龄匹配的重度VD患者7例,其中7例AD与6例VD完成了6个月的随访。用双抗体夹心ELISA检测脑脊液T-tau,P-tau231的浓度。结果:基线期AD组与VD组患者CSF T-tau的浓度分别为470.08(263.58)pg/m L、208.76(42.24)pg/m L,差异有统计学意义(Z=-3.369,p0.001);CSF P-tau231的浓度分别为90.94(49.86)pg/m L、42.96(13.10)pg/m L,差异有统计学意义(Z=-3.237,p0.001)。重度AD与重度VD相比,CSF T-tau(Z=-2.830,p=0.005)、CSF P-tau231(Z=-2.392,p=0.017)的浓度仍有统计学差异,重度AD患者CSF T-tau、CSF P-tau231的浓度比重度VD患者高。中度AD患者CSF P-tau231(Z=-2.605,p=0.009)的浓度显著高于重度AD患者。6个月随访期间,两组患者脑脊液T-tau、P-tau231浓度的变化均无统计学意义。结论:AD患者脑脊液T-tau、P-tau231与VD相比显著升高。中度AD患者CSF P-tau231显著高于重度AD患者。6个月随访期间两组患者脑脊液T-tau、P-tau231浓度的变化均无统计学意义。     

中重度阿尔茨海默病与血管性痴呆患者脑脊液tau蛋白的预研究

背景：阿尔茨海默病（Alzheimer’s disease,AD）患病率高、医疗费用高、照料困难,已成为老龄化社会面临的严重社会、经济问题。迄今,AD的诊断尚无可靠的客观诊断指标。近年来,国内外对AD患者脑脊液生物学标志物的研究甚多,AD患者脑脊液T-tau、P-tau升高已是不争的事实。但是,这些标志物与痴呆严重程度以及随病程进展的关系还有待进一步深入研究。
　　目标：比较中重度阿尔茨海默病（Alzheimer’s dis-ease,AD）与血管性痴呆（vascular demenita,VD）患者脑脊液（cerebrospinal lfuid,CSF）总tau蛋白（total tau,T-tau）和第231位苏氨酸磷酸化tau蛋白（P-tau231）的基线浓度,随访6个月,观察它们在AD患者与对照组之间的差异以及随病程进展的变化。
　　方法：基线期中度AD患者11例（10≤ MMSE ≤20）,重度AD患者10例（MMSE ≤9）以及年龄匹配的重度VD患者7例,其中7例AD与6例VD完成了6个月的随访。用双抗体夹心ELISA检测脑脊液T-tau, P-tau231的浓度。
　　结果：基线期AD组与VD组患者CSF T-tau的浓度分别为470.08（263.58）pg/mL、208.76(42.24）pg/mL,差异有统计学意义（Z=-3.369,p <0.001）;CSF P-tau231的浓度分别为90.94(49.86）pg/mL、42.96（13.10） pg/mL,差异有统计学意义（Z=-3.237,p<0.001）。重度AD与重度VD相比,CSF T-tau（Z=-2.830,p =0.005）、CSF P-tau231（Z =-2.392,p=0.017）的浓度仍有统计学差异,重度AD患者 CSF T-tau、CSF P-tau231的浓度比重度VD患者高。中度AD患者CSF P-tau231（Z=-2.605, p=0.009）的浓度显著高于重度AD患者。6个月随访期间,两组患者脑脊液T-tau、P-tau231浓度的变化均无统计学意义。
　　结论：AD患者脑脊液T-tau、P-tau231与VD相比显著升高。中度AD患者CSF P-tau231显著高于重度AD患者。6个月随访期间两组患者脑脊液T-tau、P-tau231浓度的变化均无统计学意义。     

阿尔茨海默病患者脑脊液可溶性血小板衍生生长因子受体β与认知损害及脑脊液生物标志物的相关性研究

目的研究阿尔茨海默病(AD)患者脑脊液可溶性血小板衍生生长因子受体β(sPDGFRβ)浓度与认知损害程度及脑脊液生物标志物的相关性。方法选取2018年9月至2020年8月安徽医科大学附属省立医院神经内科收治的AD患者(AD组)50例,及同期住院的认知功能正常的对照组33例,对其完善神经心理学测评,依据临床痴呆量表(CDR)评分将AD患者分为轻度AD组和中重度AD组,比较3组的临床资料、认知功能。采用酶联免疫吸附法测定各组患者的脑脊液sPDGFRβ、脑脊液β-淀粉样蛋白(Aβ)1-42、脑脊液Aβ1-40、总tau蛋白(T-tau)及磷酸化tau蛋白(P-tau)含量,比较3组间差异。将AD组根据载脂蛋白E(ApoE)基因是否携带ε4基因分为ApoE4+组和ApoE4-组,比较组间脑脊液sPDGFRβ差异。并将轻度AD组和中重度AD组、对照组脑脊液sPDGFRβ与认知损害程度和脑脊液Aβ1-42、T-tau及P-tau含量进行相关分析。结果中重度AD组脑脊液sPDGFRβ浓度[(235.358±86.187)pg/ml]和轻度AD组脑脊液sPDGFRβ浓度[(219.301±69.711)pg/ml]高于对照组[(184.878±52.944)pg/ml],差异有统计学意义(F=3.90,P=0.024)。而在AD患者中,ApoE4+组脑脊液sPDGFRβ[(219.493±76.745)pg/ml]和ApoE4-组[(222.802±81.665)pg/ml]间差异无统计学意义(t=-0.13,P=0.900)。相关分析结果显示,轻度AD组脑脊液sPDGFRβ与脑脊液P-tau水平呈正相关(r=0.43,P=0.019),与Aβ1-42、T-tau水平、简易精神状态检查量表评分及蒙特利尔认知评估量表评分无相关性,而在中重度AD组和对照组中则均无相关性。结论脑脊液sPDGFRβ在AD患者中升高,并在早期与P-tau有关;周细胞损伤可能参与了AD患者脑内tau蛋白的磷酸化。     

静脉滴注免疫球蛋白治疗多发性硬化随机对照试验的meta分析

目的 系统评价静脉滴注免疫球蛋白(intravenous immunoglobulin,IVIG)维持治疗多发性硬化(multiple sclerosis,MS)的临床疗效.方法 采崩Cochrane系统评价方法,通过电子检索MEDLINE、EMbas、CBMdisc、Cochrane Library、ISI和美国临床试验登记中心等的数据库文献(1990～2008).评价纳入文献的方法学质量后,采用RevMan 4.2.10软件对提取的数据进行分析.结果 共纳入10个随机对照试验研究.IVIG治疗组与安慰剂组比较,研究期限内复发缓解型多发性硬化(relapsing-remitting muhiple sclerosis,RRMS)患者的复发状况差异有统计学意义(P=0.04,OR:0.40.95%CI=0.19～0.86),RRMS患者EDSS评分的变化差异有统计学意义(P＜0.0001,WMD=-0.27,95%CI=-0.40～-0.13),不同剂量IVIG(每个月0.2 g/kg与0.4 g/kg)治疗RRMS的复发状况比较差异无统计学意义(P=0.69,OR=1.16,95%CI=0.56～2.41);IVIG与干扰素-β1a治疗RRMS的疗效比较,显示二者均能降低疾病的复发率,二者之间无统计学差异(P＞0.1),而在治疗前后EDSS评分的比较中,仅IVIG治疗前后的差异有统计学意义.IVIG治疗组与安慰剂组比较,研究期限内进展型MS患者的疾病进展状况差异无统计学意义(P=0.32,OR=0.68,95%CI=0.31～1.46),继发进展型多发性硬化(secondary-progressivemultiple sclerosis,SPMS)患者的复发状况差异无统计学意义(P=0.70,OR=0.93,95%CI=0.66～1.32).结论 IVIG用于维持治疗MS,其安全性好,可降低RRMS的复发率及EDSS评分显示的神经功能障碍.不同剂量的IVIG治疗RRMS无剂量-效应关系.IVIG与干扰素-β1a均能降低RRMS的复发率,IVIG改善神经功能方面的疗效优于低剂量的干扰素-β1a.目前尚不能认为IVIG用于进展型MS的维持治疗可以阻止疾病的进展及复发.     

多发性硬化患者生活质量评估及其影响因素探讨

目的评估多发性硬化患者生活质量水平,并探讨其影响因素。方法收集2012年7月~2016年12月就诊于河南省人民医院复发缓解型多发性硬化患者(relapsing-remitting MS,RRMS)36例,继发进展性多发性硬化患者(secondary progressive MS,SPMS)21例作为研究对象。采用多发性硬化生活质量54项评分(Multiple Sclerosis Quality of Life-54 instrument,MSQo L-54)测试MS患者的生活质量;对所有研究对象进行认知功能、抑郁状态、疲劳、睡眠质量及日常生活能力评估。结果 (1)RRMS组及SPMS组患者躯体生活质量(RRMS组58.62±16.32;SPMS组28.77±15.99,P=0.000)、精神生活质量(RRMS组57.33±16.72;SPMS组36.27±23.50,P=0.000)均有下降,SPMS组下降更明显。多元逐步回归法分析,与MS生活质量相关因素中,Hamilton抑郁量表评分处于第一位(β=-0.516,P<0.001),其次为反应躯体化残疾程度的EDSS评分(β=-0.372,P<0.001),第三位为疲劳评分(β=-0.250,P=0.002)。结论 MS患者有不同程度的生活质量下降,SPMS患者更明显。EDSS评分、抑郁、疲劳影响患者生活质量,早期干预抑郁及疲劳,对于改善MS患者生活质量有益。     

早期多发性硬化和视神经脊髓炎高危综合征的临床特点

目的 探讨早期多发性硬化和视神经脊髓炎高危综合征的临床特点.方法 回顾性分析我院2012-04-2014-01收治的45例早期MS患者和33例NMO高危综合征患者的临床资料,对比分析2组一般资料、机体功能评价、影像学检查和生化检查结果,总结两种疾病的临床特点.结果 2组在括约肌症状、认知障碍、小脑症状、视力受损及运动症状方面比较差异无统计学意义(P＞0.05),在病程、脑干症状、EDSS评分及感觉症状等方面比较差异有统计学意义(P＜0.05).早期MS组患者病灶数量＞9个、Barkhof标准符合率及脑MRI多发性硬化样病灶发生率均高于NMO高位综合征组,差异有统计学意义(P＜0.05).早期MS组患者脊髓病灶发生率、脑脊液白细胞计数异常率、脑脊液蛋白异常率、脑脊液蛋白水平及脑脊液白细胞计数均低于NMO高位综合征组患者,差异有统计学意义(P＜0.05).2组在钆增强扫描病灶发生率方面比较差异无统计学意义(P＞0.05).NMO高位综合征组抗体阳性率显著高于早期MS组,差异有统计学意义(P=0.018).结论 视神经脊髓炎高危综合征和早期多发性硬化具有不同的临床特点,临床诊断中应加以利用进行甄别,避免误诊的发生.     

复发-缓解型多发性硬化患者丘脑扩散张量成像研究

目的 通过扩散张量成像研究复发-缓解型多发性硬化患者常规MRI表现正常的丘脑扩散参数异常,以及与临床残疾程度和认知损害间的相关性.方法 24例复发-缓解型多发性硬化患者和与之性别、年龄相匹配的健康志愿者分别接受常规MRI和扩散张量成像检查,利用兴趣区法测量影像正常的丘脑扩散参数,比较两组受试者丘脑平均扩散率和部分各向异性间的差异性,并评价患者丘脑扩散参数与临床相关评分及病灶体积之间的相关关系.结果 复发-缓解型多发性硬化组患者丘脑平均扩散率[(85.34+14.68)x10-3mm2/s]低于正常对照组[(98.42±13.10)×10-3mm2/s],组间差异具有统计学意义(t=-3.257,P=0.002);丘脑部分各向异性(0.40±0.04)高于正常对照组(0.36±0.05),差异亦有统计学意义(t=3.163,P=0.003).复发-缓解型多发性硬化组患者丘脑平均扩散率与同步听觉连续加法测验评分呈显著正相关(r= 0.711,P=0.000).结论 对常规MRI表现正常的复发-缓解型多发性硬化患者,扩散张量成像可以发现丘脑异常.而且丘脑扩散异常与患者认知损害存在相关性,提示扩散张量成像作为评价临床功能的重要指标,具有很好的应用前景.     

脑脊液tau蛋白预测轻度认知障碍进展为阿尔茨海默病的Meta分析

目的评价脑脊液总tau(t-tau)蛋白和磷酸化tau(p-tau)蛋白预测轻度认知障碍(MCI)患者进展为阿尔茨海默病(AD)的临床价值。方法全面检索2000至2014年Pub Med、Cochrane Library、Web of Science数据库、Ovid全文电子期刊、中国知网全文数据(CNKI)和万方数据库中有关脑脊液tau蛋白预测MCI患者进展为AD的文献,收集每项研究中tau蛋白水平数据,用Stata11.0软件对数据进行Meta分析,计算合并效应量。采用Egger法对漏斗图作对称性检验评估发表偏倚、并进行敏感性分析。结果共纳入11项研究,其中9项研究完整提供了脑脊液总t-tau蛋白和p-tau蛋白浓度数据,另外2项研究仅提供了总t-tau蛋白浓度,未提供p-tau蛋白浓度。Meta分析显示:MCI进展为AD的患者脑脊液t-tau蛋白及p-tau蛋白基线浓度均高于稳定型MCI患者[t-tau:标准均数差(SMD)=1.063,95%CI:0.902~1.223,Z=13.00,P0.001;P-tau:SMD=1.335,,Z=7.44,P0.001]。结论脑脊液tau蛋白可作为预测MCI进展为AD的一项生物学指标。     

多发性硬化患者脑脊液和血清中髓鞘碱蛋白和白介素-16的相关研究

目的　了解多发性硬化 (MS)患者脑脊液 (CSF)和血清髓鞘碱性蛋白 (MBP)和白介素 16 (IL 16 )的水平 ,探讨两者之间的相关性 ,及其在MS发病过程中的作用。方法　采用ELISA法对 31例MS患者CSF和血清的MBP和IL 16进行测定 ,并与 2 4例炎性脱髓鞘性多发性神经病 (IDP)、2 2例对照者进行比较。结果　MS组CSF和血清中的MBP水平均显著高于IDP组及对照组 (均P <0 .0 1) ;CSF中的IL 16的水平显著高于对照组 (P <0 .0 1) ,而血清中IL 16水平与对照组相比无明显差异 (P >0 .0 5 )。MS组中CSF的MBP水平与IL 16水平显著相关 (r=0 .4 6 8,P <0 .0 1) ,但血清中MBP的水平与IL 16水平无相关性 (r=- 0 .131,P >0 0 5 ) ;CSF中MBP水平和血清中MBP的水平有相关性 (r=0 .5 0 5 ,P <0 .0 1) ,CSF中IL 16和血清中IL 16的水平无相关性 (r=0 .0 2 2 ,P >0 .0 5 )。结论　MBP是诱导MS发病的主要自身抗原之一 ,MBP可能主要在中枢神经系统中刺激IL 16的产生 ;而IL 16主要在中枢神经局部产生并起作用     

多发性硬化和格林-巴利综合征患者体液中TNF及IL-1水平与临床关系的研究

测定了多发性硬化(MS)和格林-巴利综合征(GBS)患者的细胞因子，发现活动的MS血清和脑脊液(CSF)TNF水平显著高于稳定的MS和对照组。GBS患者急性期CSF和血清TNF水平显著高于对照组及治疗后水平。另外，MS和GBS患者CSF的TNF水平均高于相应的血清水平。通过研究还发现MS和GBS组CSF的蛋白含量显著增高。此外，MS组CSF白细胞敷与CSF的TNF水平及CSF蛋白含量相关，且CSF蛋白含量与血清、CSF的TNF水平相关。这表明TNF一方面可能来源干鞘内的单个核细胞，另一方面由于血脑屏障受损可能来源于血液，另外还可能来源于神经肢质细胞及血管内皮细胞。TNF可能在炎性脱鞘病发病初期起作用。     

Determination of CSF guanase activity in multiple sclerosis: a comparative study on various parameters to monitor the disease activity

Forty two patients with multiple sclerosis (MS) were subjected to determination of CSF guanase activity, CSF IgG concentration, Tibbling's IgG index and Kurtzke's expanded disability status scale (EDSS) together with multimodal evoked potentials (MEPs), which consisted of somatosensory evoked potentials to arm and leg stimulation, visual evoked potential and auditory brainstem response. All patients were divided into active (n = 28) and inactive (n = 14) group, where an "active" was defined as a case revealing a relapse within one month prior to the study. The results were as follows: 1. CSF guanase activity was significantly high in active MS as compared with inactive MS (p less than 0.001), and the same trend was found in CSF IgG concentration (p less than 0.01), but not in IgG index. 2. Abnormal MEP was closely associated with elevated CSF guanase activity in active MS (p less than 0.05), but not in inactive MS. 3. In regard to the disease activity, EDSS was significantly high in active MS as compared with inactive MS (p less than 0.01), and EDSS was also significantly high in abnormal MEP group (p less than 0.001). 4. EDSS was closely correlated with CSF guanase activity in active MS (p less than 0.005), but not in inactive MS. 5. Judging from serial determinations of the parameters in 6 patients, CSF guanase activity, less susceptive to steroid hormone therapy than CSF immunoglobulin level, was found parallel to EDSS, however, both CSF IgG concentration and IgG index failed to correlated with EDSS. In summary, CSF guanase activity was thought to be a sensitive parameter in multiple sclerosis, reflecting not only the disease activity but also spatial involvement in the CNS.     

Increased levels of IL-23 and osteopontin in serum and cerebrospinal fluid of multiple sclerosis patients

Osteopontin (OPN) and interleukin-23 (IL-23) are pro-inflammatory cytokines proposed to play central roles to the development of multiple sclerosis (MS). The aim of this study was to evaluate levels of OPN, IL-23 and other inflammatory cytokines and investigate their relationships in serum and cerebrospinal fluid (CSF) in patients with MS. Fifty one MS patients and 48 patients with non-inflammatory neurological diseases (NIND) were recruited from clinic. The levels of OPN, IL-23, IL-17, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in serum and CSF were determined in each participant. Compared with NIND group, MS patients had significantly elevated levels of OPN, IL-23, IL-17 and TNF-alpha in CSF, and elevated levels of IL-23, IL-17 and TNF-alpha in serum (All P<0.001). In MS patients, OPN and IL-23 were positively correlated with IL-17 (r=0.302, P=0.019; r=0.417, P=0.001, respectively); and IL-23 was positively correlated with EDSS (r=0.329, P=0.019). Both OPN and IL-23 may play pivotal role in development of MS and might be specific markers and therapeutic targets for MS.     

Reduced CSF PLTP activity in Alzheimer's disease and other neurologic diseases; PLTP induces ApoE secretion in primary human astrocytes in vitro

Phospholipid transfer protein (PLTP) plays a pivotal role in cellular lipid efflux and modulation of lipoprotein metabolism. PLTP is distributed widely in the central nervous system (CNS), is synthesized by glia and neurons, and is active in cerebrospinal fluid (CSF). The aims of this study were to test the hypothesis that patients with Alzheimer's disease (AD) have altered PLTP-mediated phospholipid transfer activity in CSF, and to examine the potential relationship between PLTP activity and apolipoprotein E (apoE) levels in CSF. We assessed PLTP activity and apoE concentration in CSF of patients with probable AD (n = 50), multiple sclerosis (MS; n = 9), other neurologic diseases (n = 21), and neurologically healthy controls (n = 40). PLTP activity in AD was reduced compared to that in controls (P < 0.001), with approximately half of the AD patients with PLTP activity values below all controls. Patients with MS had lower PLTP activity than AD patients (P < 0.001). PLTP activity was highly correlated with PLTP mass, as estimated by Western blot (r = 0.006; P < 0.01). CSF PLTP activity positively correlated with apoE concentration in AD (R = 0.435; P = 0.002) and controls (R = 0.456; P = 0.003). Anti-apoE immunoaffinity chromatography and Western blot analyses indicated that some CSF PLTP is associated with apoE-containing lipoproteins. Exogenous addition of recombinant PLTP to primary human astrocytes significantly increased apoE secretion to the conditioned medium. The findings of reduced PLTP activity in AD CSF, and the observation that PLTP can influence apoE secretion in astrocytes suggest a potential link between alterations in the brain lipid metabolism and AD pathogenesis.     

Increased frequency of chromosome aberrations in long-term cultured cerebrospinal fluid lymphocytes of patients with multiple sclerosis

A method employing long-term lymphocyte culturing was developed to study chromosome aberrations in samples with very few cells. It was used to examine lymphocytes from the cerebrospinal fluid (CSF) and peripheral blood (PB) in 23 patients with clinically definite multiple sclerosis (MS), nine patients with other neurological diseases (OND), and eight healthy individuals. MS patients had significantly more aberrations in CSF lymphocytes than in PB lymphocytes (6.4 vs 4.1; P = 0.003). In contrast, no such difference was noted among patients with OND (3.8 vs. 3.7; P = 0.89) or healthy controls (3.6 vs 3.5; P = 0.90). CSF lymphocytes from MS patients had more aberrations than CSF lymphocytes from healthy controls (P = 0.012), but there was no difference between PB lymphocytes from MS patients and controls (P = 0.58). The patients with OND were similar to healthy controls both in CSF (3.8 vs 3.6; P = 0.91) and PB lymphocytes (3.7 vs 3.5; P = 0.90).     

多发性硬化、视神经脊髓炎患者血清及脑脊液中脑源性神经营养因子与胶质细胞源性神经营养因子水平

目的 探讨多发性硬化(MS)、视神经脊髓炎(NMO)患者血清及脑脊液中脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)水平及其神经保护作用.方法 对62例MS、NMO患者及21例对照者进行研究,患者组复发期进行扩展残疾状态量表(EDSS)评分、MRI检查及寡克隆带测定,液相芯片分析技术检测血清及脑脊液BDNF、GDNF浓度.结果 MS、NMO患者复发期血清及脑脊液BDNF(μg/L,MS患者:5.616±0.650、0.186±0.012;NMO患者6.584±0.929、0.176±0.006)、GDNF浓度(μg/L,MS患者:0.039、0.080;NMO患者0.029、0.050)与对照组(μg/L,血清:4.374±0.501、0.040;脑脊液:0.152±0.011、0.065)比较差异无统计学意义;脑脊液BDNF与GDNF浓度水平呈正相关(r=0.756,P=0.000),血清BDNF与GDNF浓度水平呈负相关(r=-0.329,P=0.018).血清及脑脊液BDNF、GDNF浓度与EDSS评分、血脑屏障指数、Delpech指数及Tourtellotte合成率无明显相关性.有或无脑萎缩的MS、NMO患者血清及腩脊液BDNF、GDNF浓度差异无统计学意义.结论 MS、NMO患者体内BDNF与GDNF水平相关,二者可能具有协同的神经保护作用.BDNF及GDNF与NMO、MS患者血脑屏障破坏及中枢神经系统内IgG合成无关,与神经功能残疾及脑萎缩的关系仍需研究.     

In vivo relationship of tumor necrosis factor-α to blood-brain barrier damage in patients with active multiple sclerosis

Tumor necrosis factor-alpha (TNF-alpha) has well recognized effects on cerebral endothelial cells and, therefore, may mediate disruption of blood-brain barrier in patients with multiple sclerosis (MS). To evaluate the in vivo relationship of TNF-alpha to blood-brain barrier impairment in MS, levels of this cytokine in cerebrospinal fluid (CSF) and serum samples from 38 patients with active MS and 48 controls were correlated with CSF to serum albumin ratios. TNF-alpha was detected in the serum of 74% and the CSF of 66% of patients with active MS. CSF levels of TNF-alpha were significantly higher in active MS compared to stable MS or other controls, and were significantly higher than corresponding serum levels. In patients with active MS, only those with detectable TNF-alpha showed signs of blood-brain barrier damage. Moreover, intrathecal levels of TNF-alpha in active MS correlated with albumin ratios and with the degree of barrier damage. Our findings are important in understanding some of the pathological changes in active multiple sclerosis.     

IL-15 is elevated in serum and cerebrospinal fluid of patients with multiple sclerosis

Interleukin-15 (IL-15) is a novel proinflammatory cytokine having similar biological activities to IL-2 which is implicated in the pathogenesis of multiple sclerosis. It is produced by activated blood monocytes, macrophages and glial cells. There is little information about the involvement of IL-15 in the development of multiple sclerosis (MS). The objective of our study was to measure IL-15 serum and cerebrospinal fluid (CSF) levels in MS patients and to correlate serum and CSF IL-15 concentrations with clinical parameters of the disease. CSF IL-15/Serum IL-15 ratio (c/s IL-15 ratio) was introduced to assess the origin of elevated IL-15 levels. MATERIALS AND METHODS: We measured serum and CSF IL-15 levels in 52 patients with MS and 36 age and gender matched patients with inflammatory (IND) and non-inflammatory neurological diseases (NIND) studied as control groups. IL-15 levels were correlated with clinical parameters as duration, disability, MRI activity and clinical subtypes of the disease. RESULTS: MS patients were found to have significantly higher serum IL-15 levels compared with IND (p=0.00016) and NIND patients (p=0.00045). Elevated levels of IL-15 were also found in CSF samples from MS patients compared with patients with IND (p=0.00034) and NIND (p=0.0003). Among MS subgroups there were no statistically different IL-15 serum and CSF concentrations. No significant correlation of serum and CSF IL-15 concentrations with MRI activity, disability assessed by EDSS score and duration of the disease were also found. C/S IL-15 ratio was found lower in MS patients compared with IND (p=0.01) and not significantly different compared with NIND patients (p=0.14) suggesting that systemic activation might be the source of high CSF IL-15 levels in MS patients. CONCLUSIONS: Our findings suggest a possible role of IL-15 in the immunopathogenetic mechanisms of MS.