硫辛酸治疗中枢神经系统脱髓鞘疾病的疗效观察

目的观察硫辛酸治疗中枢神经系统炎性脱髓鞘疾病的临床疗效。方法选取在我院就诊的48例缓解期视神经脊髓炎与多发性硬化患者为研究对象,根据病程是否1a分为短病程组和长病程组,均给予硫辛酸胶囊口服治疗,分别采用扩充神经功能残疾量表评估患者治疗前、治疗1个月、3个月后的日常生活能力,并进行对比。结果 2组治疗1、3个月后神经功能评分均比治疗前明显降低,差异有统计学意义(P0.05),长病程组治疗前、后的神经功能评分均大于短病程组,差异有统计学意义(P0.05)。2组治疗前与治疗后1个月、治疗后1个月与治疗后3个月的神经功能评分之差比较,差异无统计学意义(P0.05)。但长病程组神经功能评分的改善程度均显著差于相应时间段的短病程组,差异有统计学意义(P0.05)。结论硫辛酸治疗中枢神经系统脱髓鞘疾病效果良好,早期治疗和长期服用效果更明显,不良反应少且轻微,可作为中枢神经系统脱髓鞘疾病缓解期新的治疗方法。     

维生素D_3添加治疗复发型多发性硬化的临床随机对照研究

目的采用临床随机对照研究维生素D3添加治疗复发型多发性硬化(MS)患者的临床疗效和安全性。方法缓解复发型MS患者72例,随机分成维生素D3组(甲泼尼龙+维生素D3治疗)和激素组(甲泼尼龙治疗,为对照),每组36例,维生素D3组在激素治疗基础上添加骨化三醇胶丸口服。治疗前后记录症状、体征,评定扩展残疾状态评分(EDSS)分值,治疗后随访2年。疗效评定考核指标采用MS年复发次数,复发间隔时间,EDSS评分下降值。结果治疗前维生素D3组年龄、病程、复发次数、EDSS数值与激素组比较,差异无统计学意义(P0.05);治疗后第6、12个月EDSS数值与激素组比较,差异也无统计学意义(P0.05)。治疗后第24个月,维生素D3组与激素组比较EDSS数值(P0.05)、年复发次数(P0.05)、复发间隔时间(P0.01),差异有统计学意义。结论维生素D3添加治疗能减少MS的复发次数、延长复发间歇时间、延缓残疾进展速度。     

多发性硬化患者血清维生素D水平变化及与临床相关性研究

目的观察多发性硬化(MS)患者体内维生素D水平,探讨维生素D水平与MS临床表型的关系。方法收集MS患者72例,包括复发缓解型MS(RRMS)62例、继发进展型MS(SPMS)7例及原发进展型MS(PPMS)3例;视神经脊髓炎(NMO)患者24例;以32名健康体检者为健康对照组(NC组)。采用电化学发光法对血清25-羟维生素D_3[25-hydroxyvitamin D_3,25(OH)D_3]进行检测,所有MS患者在留取血标本的同时进行扩展残疾状态量表(EDSS)评分,对其中15例急性复发期RRMS患者在缓解期再次行血清25(OH)D_3检测和EDSS评分。结果 MS组、NC组及NMO组间血清25(OH)D_3水平比较差异有统计学意义(F=10.55,P0.01),MS组及NMO组均低于NC组(分别P0.01,P0.05),但MS组与NMO组相比差异无统计学意义(P0.05);SPMS患者血清25(OH)D_3水平低于NC组(P0.01),但与RRMS患者比较无统计学差异(P0.05);RRMS患者血清25(OH)D_3水平缓解期高于急性复发期(t=2.92,P0.05),但仍低于NC组(P0.01)。结论 MS及NMO患者体内维生素D不足,且维生素D不足贯穿于MS的不同病程阶段,RRMS患者急性复发期维生素D不足更为明显。     

脑脊液BAFF、VEGF水平在视神经 脊髓炎患者中的变化及其意义

目的 探讨脑脊液B淋巴细胞活化因子(BAFF)、血管内皮生长因子(VEGF)水平在视神经脊髓炎(NMO)患者中的变化及其意义。方法 选取2015年1月-2018年1月本院收治的NMO患者50例作为NMO组,选取同期多发性硬化症(MS)患者50例作为MS组及非炎性神经系统疾病患者50例作为对照组,所有患者均检测脑脊液BAFF、VEGF水平、急性期扩展残疾状态量表(EDSS)评分、水通道蛋白4抗体(AQP4-Ab)滴度,分析BAFF、VEGF与EDSS评分、AQP4-Ab滴度的关系。结果 NMO组和MS组脑脊液BAFF、VEGF水平明显高于对照组,NMO组脑脊液BAFF、VEGF水平和EDSS评分、AQP4-Ab滴度阳性率明显高于对照组(P<0.05); Pearson相关性分析显示,脑脊液BAFF、VEGF水平均与EDSS评分呈正相关(r=0.695,0.668,P<0.05),但均与AQP4-Ab滴度无关(r=0.121,0.116,P>0.05)。结论 脑脊液BAFF、VEGF水平与NMO的发生发展有关,检测二者水平可作为鉴别NMO、MS及评估NMO病情的重要参考指标。     

肿瘤坏死因子β水平与多发性硬化临床表现的相关性

目的 探讨肿瘤坏死因子(TNF)β水平与多发性硬化(MS)临床表现的相关性.方法 应用双抗体夹心酶联免疫法测定58例MS患者(MS组)血清TNFβ水平;并与患者不同亚型、病期、神经功能缺损程度的扩展病残状态评分(EDSS)、病程、发病次数、发病年龄等临床情况进行相关性分析.结果 (1)MS组急性期TNFβ水平较缓解期和正常对照组显著升高(P<0.05～0.01);MS缓解期与正常对照组间差异无统计学意义.(2)MS西方型急性期TNFβ水平较缓解期显著升高(P<0.01);MS亚洲型急性期与缓解期差异无统计学意义.(3)两亚型急性期、缓解期TNFβ水平与其EDSS、病程、发病次数及发病年龄均无相关性.结论 (1)TNFβ水平与MS急性期存在相关,MS西方型急性期、缓解期变化更显著.(2)TNFβ水平与EDSS、病程、发病次数及发病年龄可能不相关.     

干扰素β-1b对多发性硬化患者生活质量影响的1年随访

目的观察干扰素β-1b(IFNβ-1b)治疗复发缓解型多发性硬化(MS)患者的疗效并进行生活质量评估,进一步探索生活质量的相关因素。方法选择接受IFNB-1b治疗的MS患者13例,并于治疗后第1个月、3个月、6个月、9个月、12个月对患者进行随访,评估包括扩展的功能缺损状况(EDSS)评分、多发性硬化患者生活质量量表(MSQOL-54)及汉密尔顿焦虑抑郁量表(HAMA、HAMD)评分。结果经IFNB1b治疗的MS患者在第1、3、6、9、12个月随访时生活质量、EDSS、HAMA、HAMD评分与治疗前比较均无明显变化(P0.05)。治疗前生活质量中躯体功能、性功能及对性生活满意度与EDSS评分呈负相关(P值均0.05);情绪致角色受限、疼痛与病程呈正相关(P值均0.05);躯体功能、情绪状况、社会功能、性功能及对性生活满意度与HAMA评分呈负相关(P值均0.05);认知、应激与HAMD评分均呈负相关(P值均0.05)。躯体致角色受限、精力、健康认知、总体生活质量及健康变化与病程、EDSS、HAMA、HAMD各项无相关性,年龄与MSQOL-54无关(P值均0.05)。结论 IFNB-1b短期内可能对MS患者生活质量无明显影响,生活质量与患者的EDSS评分、焦虑抑郁症状相关。     

多发性硬化SF-36的影响因素分析

目的探讨多发性硬化(MS)"健康调查简易量表"(SF-36)的影响因素。方法对比分析MS不同间歇期、发作期、Zung抑郁自评量表(SDS)评分指数、焦虑自评量表(SAS)评分、扩充神经功能残疾量表(EDSS)评分及病程等SF-36各维度,如生理功能(PF)、情感职能(RE)、社会功能(SF)、精神健康(MH)、生理职能(RP)、精力(VT)、躯体疼痛(BP)、总体健康(GH)等参数,提出MS者SF-36的影响因素。结果 MS患者间歇期越缩短、发作期及病程越延长、SDS及SAS和EDSS评分越高,SF-36各维度评分越降低(P0.05或P0.01)。结论间歇期、发作期、SDS评分指数、SAS及EDSS评分、病程等直接影响MS患者的生活质量。     

中枢神经系统特发性炎性脱髓鞘疾病患者血清尿酸改变的临床分析

目的 探讨血清尿酸（UA）与中枢神经系统特发性炎性脱髓鞘疾病（IIDDs）[包括多发性硬化（MS）、视神经脊髓炎（NMO）、急性播散性脑脊髓炎（ADEM）、临床孤立综合征（CIS）]的关系.方法 选择IIDDs患者100例为病例组,其中MS组30例、NMO组18例、ADEM组25例、CIS组27例.另选取非炎性神经系统疾病40例为对照组.采用酶比色法测定各组血清UA.比较病例组与对照组UA值,并分析MS组患者尿酸与Kurtzke扩展残疾状态量表（EDSS）评分相关性.结果 MS组、NMO组、ADEM组、CIS组患者血清UA值均较对照组明显降低（均P＜0.05）;MS组患者EDSS评分与UA值呈负相关（P＜0.01）.结论 除MS外,NMO、ADEM、CIS患者也存在UA水平降低;MS患者UA水平降低与其临床神经功能缺损的严重程度有关;提示低UA血症可能是IIDDs的独立危险因素,间接证实了UA在IIDDs中的保护性作用.     

视神经脊髓炎患者血清及脑脊液中B淋巴细胞活化因子的表达水平与临床意义

目的 探讨视神经脊髓炎患者血清及脑脊液中B淋巴细胞活化因子的表达水平及其临床意义。方法 选取2011年1月-2015年1月本院收治的视神经脊髓炎(NMO)患者50例及多发性硬化(MS)患者50例,将其分别作为NMO组与MS组,另选取同期于本院进行体检的非炎性神经系统疾病患者50例作为对照组,对3组血清及脑脊液中的B淋巴细胞活化因子(BAFF)水平进行检测。结果 与对照组比较,NMO组与MS组血清中BAFF水平均无明显变化(P>0.05),而NMO组与MS组脑脊液中BAFF水平均明显升高(P<0.05); 与MS组比较,NMO组脑脊液中BAFF水平明显升高(P<0.05)。NMO组与MS组脑脊液中BAFF水平与EDSS评分呈正相关,即脑脊液中BAFF水平随EDSS评分升高而升高(r=0.887,0.885,P<0.01)。结论 视神经脊髓炎患者脑脊液中的B淋巴细胞活化因子水平较高,可能是诊断视神经脊髓炎的重要标志物,对疾病严重程度的判定具有重要的临床意义。     

视神经脊髓炎患者生活质量调查

目的观察视神经脊髓炎(neuromyelitis optica,NMO)患者扩展残疾状况量表(expanded disability status scale,EDSS)评分、病程、年龄、性别及水通道蛋白4(AQP4)-IgG与生活质量的关系,初步探讨影响NMO患者生活质量的因素。方法对40例NMO患者进行EDSS评分,填写国外广泛使用于NMO患者的中文版简化36医疗结局研究量表(MOSSF-36,简称SF-36量表),分别对NMO患者的EDSS评分、病程、年龄、AQP4-IgG与SF-36量表评分的相关性进行分析。结果 NMO患者EDSS评分与生活质量中生理健康呈中度负相关(r=-0.572,P=0.0001),与心理健康无相关性(r=-0.284,P=0.075)。其中EDSS评分与SF-36量表8个维度中的生理机能(r=-0.484,P=0.002)、生理职能(r=-0.532,P=0.0004)、躯体疼痛(r=-0.386,P=0.014)、一般健康状况(r=-0.420,P=0.007)、精力(r=-0.378,P=0.016)和社会功能(r=-0.373,P=0.018)均呈负相关,与"健康变化"这一项呈低度正相关(r=0.347,P=0.028),而与"情感职能"和"精神健康"两项无相关性(均P0.05)。年龄仅与生理健康(r=-0.390,P=0.013)和其中生理功能(r=-0.498,P=0.001)这一维度呈负相关,病程、性别、AQP4-IgG与生活质量均无相关性(均P0.05),EDSS评分与年龄呈低度正相关(r=0.384,P=0.015)。结论 EDSS评分可作为NMO患者生活质量尤其是生理健康的一个预测因子,临床可常规评定NMO患者EDSS得分,从而指导临床医生关注患者生活质量并进行必要干预。     

三种抗抑郁药物改善脑卒中后抑郁及神经功能恢复的疗效对比

目的 对比舒肝解忧胶囊、盐酸文拉法辛、百忧解对脑卒中后抑郁及神经功能恢复的疗效及安全性,指导临床用药.方法 将我院收治有抑郁状态的脑卒中患者120例随机分成4组,分别为对照组和3个实验组,每组各30例.同时无抑郁状态组30例.实验组分别用舒肝解郁胶囊、盐酸文拉法辛、百忧解治疗,并于治疗前后行 HAMD、BI、SSS量表评分.结果 3个实验组的HAMD评分较对照组均有改善,其中盐酸文拉法辛改善程度最大,与其他相比差异有统计学意义（P〈0.05）.同时实验组ADL、SSS评分也明显优于对照组 （P〈0.05）,而百忧解组与其他组比较差异有统计学意义（P〈0.05）.结论 舒肝解忧胶囊、盐酸文拉法辛、百忧解这三种常用抗抑郁药物对脑卒中后抑郁状态的改善及神经功能康复均有促进作用,盐酸文拉法辛在改善抑郁状态方面有更明显作用,百忧解则更能促进脑卒中后患者神经功能康复.     

多奈哌齐合并复方海蛇胶囊治疗阿尔茨海默病性痴呆患者对照研究

目的:探讨多奈哌齐合并复方海蛇胶囊对阿尔茨海默病(AD)患者认知功能和行为能力的改善作用。方法:90例AD患者随机分为3组:联合治疗组(给予多奈哌齐合并复方海蛇胶囊治疗)30例、多奈哌齐治疗组(单用多奈哌齐治疗)30例、对照组(仅予常规治疗,不予痴呆药物)30例。观察3个月。分别在治疗前和治疗3个月后采用简易精神状态检查量表(MMSE)及日常生活能力量表(ADL)测评3组患者的认知功能和生活能力。结果:治疗3个月,联合治疗组MMSE减分值明显高于多奈哌齐治疗组(t=5.09,P0.01)和对照组(t=7.71,P0.01);多奈哌齐治疗组减分值明显高于对照组(t=3.10,P0.01)。联合治疗组ADL评分减分值明显高于多奈哌齐治疗组(t=-2.33,P=0.02)和对照组(t=-6.88,P0.01);多奈哌齐治疗组减分值明显高于对照组(t=-5.50,P0.01)。结论:多奈哌齐和复方海蛇胶囊联合治疗对AD患者的认知功能及行为能力有显著的改善作用。     

脑源性神经营养因子Val66Met功能基因多态性与抗抑郁剂疗效

目的：探讨脑源性神经营养因子（BDNF）Val66Met功能基因多态性与抗抑郁剂临床疗效的相关性。方法：302例抑郁症患者给予抗抑郁剂治疗8周。于治疗前和治疗2、4、6、8周后采用汉密尔顿抑郁量表（HAMD）评定抑郁严重程度和疗效。以治疗后HAMD总分≤7分为临床痊愈,将302例患者分为痊愈组160例和未痊愈组142例,抽取患者静脉血,采用Illumina GoldenGate定制芯片分析BDNFVal66Met基因多态性并进行基因分型。结果：痊愈组基因型分布A/A31例（19.4%）、A/G92例（57.5%）和G/G37例（23.1%）,未痊愈组分别为28例（19.7%）、78例（54.9%）和36例（25.4%）（χ2=0.054,P=0.817）;痊愈组等位基因频率分布A154例（48.1%）和G166例（51.9%）,未痊愈组分别为134例（47.2%）和150例（52.8%）（χ2=0.247,P=0.884）。3种BDNFVal66Met基因型患者间在性别、年龄、受教育年限、病程、发病次数、有无精神疾病家族史、HAMD基线及减分率上差异均无统计学意义（P均〉0.05）。结论：BDNFVal66Met基因多态性不是影响抗抑郁剂治疗近期疗效的主要因素。     

Treatment of progressive forms of multiple sclerosis by cyclophosphamide: a cohort study of 490 patients

There are no generally effective disease-modifying drugs for progressive forms of multiple sclerosis (MS). Some MS centres use cyclophosphamide (CYC) in secondary progressive (SP) forms of MS, especially after interferon beta-1b (INFbeta-1b) treatment failure. Moreover, there are currently no approved drugs for primary progressive (PP) MS. Using the collected data of patients with progressive MS, we studied clinical patterns that predicted a good response to CYC treatment. Secondly, we compared the therapeutic response of SPMS and PPMS patients to the treatment. Data from 490 MS patients were collected. All patients presented an SP (n = 362) or PP (n = 128) form of the disease and 476 had been treated for at least one year with a monthly pulse of CYC associated with methylprednisolone (MP). CYC treatment was justified because of at least a 1-point worsening on the Expanded Disability Status Scale (EDSS) during the previous year. The EDSS score was assessed at baseline and after 6 months (M6) and 12 months (M12) of treatment. After 12 months of CYC treatment, 78.6% of SPMS and 73.5% of PPMS patients had stabilised or had an improved EDSS score. Response to CYC was not significantly different in the two progressive forms of MS. Twenty-two patients presented noticeable drug side effects, one of whom withdrew from the treatment due to intolerance. Patients with an improved EDSS at M12 had a shorter mean progressive time course (5.1 years) than patients who stabilised or worsened (7.1 years) (p = 0.02). We also observed that poor responders at M6 were also poor responders at M12 (p < 0.001). This large cohort study showed that CYC treatment was well tolerated and suggested that a better response occurred in cases with a short progressive time course. We did not find any difference in treatment response between the two progressive forms of MS. To date, no treatment is approved for PPMS and we therefore propose a trial to test the use of CYC treatment early in the course of the disease in PPMS patients with disability progression.     

IFN-β-1a治疗多发性硬化的多中心前瞻开放对照研究

目的 客观观察和评定利比（Rebif,IFN-β-1a）治疗缓解复发型多发性硬化（RRMS）的临床疗效和安全性.方法 60例依据McDonald（2005）标准确诊的RRMS患者纳入利比组（其中疗程6月者38例,疗程12月12例,18月6例,24月4例）,同一时期内性别、年龄、病程和EDSS分值相匹配的60例RRMS患者纳入对照组.利比组RRMS患者接受利比44 μg皮下注射,每周3次,疗程6-24月.对照组患者口服转移因子治疗.每位入选患者在治疗前记录症状、体征、实验室及MRI检查资料,评定EDSS分值.治疗后每3月随访1次,除记录治疗前项目外,增加利比副反应.随访观察期为2年.疗效评估终点选择在（1）治疗后6月;（2）治疗后12月;（3）治疗后18月;（4）治疗后24月.疗效评定考核指标采用（1）MS年平均复发次数;（2）复发间隔时间;（3）EDSS下降值.结果 利比组患者年平均复发次数为（0.57±0.11）次,对照组为（1.23±0.20）次（P〉0.001）.利比组复发间隔时间为（464.7±20.8）d,对照组为（275.4±16.4）d（P〉0.001）.利比组RRMS患者在利比治疗6、12、18、24月后EDSS分别下降（0.48±0.08）、（0.52±0.06）、（0.93±0.08）、（1.05±0.10）分;对照组分别下降（0.23±0.09）、（-0.29±0.08）、（-0.62±0.12）、（-1.12±0.11）分,2组比较有显著差异（P〉0.001）.利比组有4例（6.67%）出现注射部位红肿,4例（6.67%）出现流感样症状,2例（3.33%）转氨酶轻度增高.此三类副反应均较轻微,2周后自行消失,仅个别患者需要对症处理.结论 RRMS患者在缓解期使用利比44 μg,每周3次皮下注射,能够显著减少MS的复发次数、延长复发间歇时间、延缓残疾进展速度;利比注射时间越长效果越好.利比治疗RRMS安全有效.     

Utilization of the multiple sclerosis functional composite in follow-up: relationship to disease phenotype, disability and treatment strategies

As multiple sclerosis (MS) has a dynamic process, monitoring of the disability is important in the remission period. The main aim of the present study was to investigate the usefulness of MSFC instead of EDSS in the follow-up period of MS. In addition, evaluation of the effect of immunomodulatory therapy, and the difference among the type of MS in follow-up was purposed. One hundred and eighty-three patients with definite MS were enrolled in the present study. Patients were diagnosed as having relapsing-remitting (RR) MS (n=149) or secondary progressive (SP) MS (n=34). Fifty-eight out of 149 RRMS patients who had at least two relapses in the last 2 years have received any of the immunomodulator agents. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) were performed at baseline and after 2 years to assess disability. Patients who were under disease modifying therapy were assessed before the treatment and 2 years after starting the treatment. Cross-sectional correlations between MSFC and EDSS score at baseline and follow-up were studied. Patients were divided into three subgroups: (1) RRMS patients who did not receive disease modifying therapy (DMT)--non-DMT group, (2) RRMS patients who received DMT--DMT group, (3) SPMS patients who did not receive DMT--SPMS group. EDSS and MSFC scores got worsened significantly at the end of the second year. Decreases in either EDSS or MSFC scores were more prominent in SPMS group. The most significant worsening was found in T25WT. The most prominent and significant decrease was in PASAT of SPMS group. Moderately strong cross-sectional correlations were found between MSFC and EDSS scores at baseline and follow-up. The most prominent correlation was between EDSS and T25WT scores with an excellent correlation. We concluded that the MSFC assesses aspects of neurological function not measured by the EDSS, suggesting that it is more sensitive to detect change over time and better able to demonstrate a therapeutic effect. The pattern of correlations among the MSFC, its components, and the EDSS supported the validity of MSFC.     

Clinical follow-up of 304 patients with multiple sclerosis three years after mitoxantrone treatment

The objectives of this study were to assess the benefits of 1) mitoxantrone after three years of follow-up and 2) disease-modifying treatment (DMT) after stopping mitoxantrone. A retrospective analysis was performed on 304 patients with active relapsing-remitting (RR) or progressive multiple sclerosis (PMS) who were treated with mitoxantrone. After mitoxantrone therapy, some patients received DMT (interferon-beta or glatiramer acetate) while others did not. The disease course of the two groups was evaluated by the Expanded Disability Status Scale (EDSS) before and after mitoxantrone and then every year for three years. The mean EDSS score at starting mitoxantrone and three years after stopping mitoxantrone respectively, were: 3.3 (1.3) and 3.2 (1.7) for the RRMS patients and 5.9 (1.2) and 6.4 (1.4) for the PMS patients. Before starting mitoxantrone, demographic and clinical parameters of predictive disability were not significantly different between patients who received DMT or not. The variation of EDSS between time of stopping mitoxantrone and three years later was significantly different (+0.9 versus +0.3; P=0.03) for patients with RRMS. We found that mitoxantrone treatment induces stable disease up to two years after discontinuation of mitoxantrone therapy. In the third year, patients without DMT deteriorated.     

硫辛酸注射液治疗2型糖尿病耳鸣患者的疗效分析

目的探讨硫辛酸注射液治疗2型糖尿病患者耳鸣的临床疗效。方法对照组10例接受腺苷钴胺、血栓通治疗,研究组11例在对照组基础上加用硫辛酸注射液,评价2组治疗效果。结果研究组总有效率（81.8%）明显高于对照组（30%）,治疗过程中未发现不良反应。结论硫辛酸注射液治疗2型糖尿病患者耳鸣临床疗效显著,且具有良好的安全性。