低剂量利妥昔单抗治疗视神经脊髓炎谱系疾病的长期疗效

目的 观察低剂量利妥昔单抗治疗视神经脊髓炎谱系疾病(NMOSD)的长期疗效。方法 回顾性收集2008年1月至2018年11月解放军总医院收治的NMOSD患者76例,其中男14例,女62例。根据治疗方案将患者分为利妥昔单抗(RTX)组(n=23)、硫唑嘌呤(AZA)组(n=32)及吗替麦考酚酯(MMF)组(n=21)。对患者进行长期随访,比较不同药物干预组患者间以及水通道蛋白4(AQP-4)抗体阳性与阴性患者间治疗前后扩展的残疾功能状态评分(EDSS)、年复发率(ARR)的差异,并记录各组患者不良反应情况。采用Kaplan-Meier生存分析比较不同药物组患者的复发情况。结果 AQP4-Ab阳性或阴性患者3种药物治疗组间治疗前及治疗后EDSS评分和ARR比较均无统计学差异(均P>0.05)。与治疗前比较,AQP4-Ab阳性或阴性患者经不同药物治疗后其EDSS评分和ARR均下降(P<0.05,P<0.01)。RTX组、AZA组及MMF组患者治疗后其EDSS评分和ARR下降程度比较均无统计学差异(均P>0.05)。Kaplan-Meier生存分析结果显示RTX组患者累...     

利妥昔单抗治疗长脊髓损害的初步分析

目的探讨利妥昔单抗治疗长脊髓损害(LESCL)的临床疗效及安全性。方法收集2010年首都医科大学宣武医院神经内科经糖皮质激素治疗无效的LESCL住院患者2例,治疗前2例患者扩展残疾状态量表(expanded disability status scale,EDSS)评分均为8.5分。对两患者均予利妥昔单抗500mg治疗1次,并随访6个月。分别于治疗后1周检测患者的淋巴细胞亚群CD19+CD20+细胞比例,评价治疗后6个月时的EDSS评分,并观察治疗期间(治疗之后至6个月)有无发热、寒战、低血压等不良反应。结果应用利妥昔单抗治疗1周后,两患者淋巴细胞亚群CD19+CD20+细胞比例均为0.00%。6个月后随访,病例1和病例2的EDSS评分分别为6.5分和2.5分,两患者均无明显不良反应。结论利妥昔单抗可能是一种治疗LESCL的有效药物。     

减量利妥昔单抗治疗视神经脊髓炎谱系病的疗效和安全性观察

目的探讨减量利妥昔单抗(华山方案)治疗视神经脊髓炎谱系病(NMOSD)的疗效,并观察其安全性。方法分析2011年1月至2017年6月在复旦大学附属华山医院神经内科住院并使用减量利妥昔单抗治疗方案的18例NMOSD患者的临床资料。减量利妥昔单抗治疗方案为静脉滴注利妥昔单抗100 mg(第1天)+500 mg(第2天),之后定期随访患者外周血总B细胞百分比,超过阈值时给予追加500 mg的后续治疗。比较患者治疗前、后的年复发率判断治疗效果;并分析减量利妥昔单抗治疗方案使用后患者出现的不良反应及耐受情况。结果减量利妥昔单抗治疗后NMOSD患者的年复发率从治疗前的1. 53减少至治疗后的0. 39 (P 0. 001)。所有病例未出现致残、致死的严重不良反应。44. 4%(8/18例)患者无任何不适,报告的不良反应主要为乏力和嗜睡(4/10例)。结论减量利妥昔单抗是NMOSD有效、耐受性好、安全性高的治疗方法之一。     

托珠单抗治疗难治性视神经脊髓炎谱系疾病的疗效与安全性初步观察

目的观察托珠单抗治疗难治性视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorder,NMOSD)的疗效与安全性。方法纳入6例血清水通道蛋白抗体(anti-aquaporin-4 antibody,AQP4-Ig G)阳性且经糖皮质激素联合硫唑嘌呤治疗疗效不佳的NMOSD患者,予托珠单抗治疗(8 mg/kg,每个月1次静脉滴注,连续治疗1年以上),前瞻性评估患者的年复发率(annualized relapse rate,ARR)、扩展残疾状态量表评分(expanded disability status scale score,EDSS)及疼痛数字评价量表(numerical rating scales,NAS),评价托珠单抗的疗效及副作用。结果 5例女性和1例男性,年龄34~63岁,病程16~96个月,托珠单抗治疗6~16次,经治疗后平均ARR由1.28±0.58降为0(P0.05),平均EDSS评分由5.50±2.81降为3.83±3.48(P0.05),平均NAS评分由5.83±3.06降为2.5±2.07(P0.05),无严重不良反应发生。结论托珠单抗可改善难治性NMOSD患者的年复发率及神经病理性疼痛,可能是一种治疗难治性NMOSD的有效药物。     

一项B细胞监测下减量利妥昔单抗治疗视神经脊髓炎谱系病的前瞻性研究

目的观察B细胞监测下减量利妥昔单抗方案治疗视神经脊髓炎谱系病(NMOSD)患者的疗效及安全性。方法收集2016年12月-2019年6月苏州大学附属第一医院神经内科规律随访的35例NMOSD患者临床资料,分为B细胞监测下减量利妥昔单抗组、硫唑嘌呤组及环磷酰胺组,比较治疗前后扩展残疾状态量表评分差值、未复发的可能性、药物不良反应等指标。结果 (1) RTX组比AZA组治疗前后EDSS评分下降水平明显,具有统计学意义(P 0.05);(2) RTX组和CTX组的复发风险明显低于AZA组,差异有统计学意义(Log-rankχ2=9.147,P=0.01);(3) RTX组总不良事件发生比例较CTX组少,RTX组激素停药率高于AZA组和CTX组(P 0.05),差异具有统计学意义;(4) RTX组平均用药间隔时间7.00(6.0,10.0) m。结论 B细胞监测下减量利妥昔单抗方案治疗NMOSD总体安全、有效,可延长用药间隔,减少患者的用药费用支出。     

利妥昔单抗治疗视神经脊髓炎的有效性及安全性分析

目的探讨利妥昔单抗对视神经脊髓炎患者的治疗效果,并分析其安全性。方法视神经脊髓炎患者65例,随机分为研究组25例,对照组40例。研究组在急性期激素冲击治疗的基础上,缓解期给予利妥昔单抗治疗。对照组给予激素冲击治疗,缓解期给予环磷酰胺静滴。治疗前及治疗8周后行EDSS部分子项目评分,进行肌力检查、中国视力表检查、日常生活活动能力评定,观察利妥昔单抗治疗后的不良反应。随访1a,了解有无复发。结果治疗8周后,研究组肌力、视力、日常生活活动能力明显提高,优于对照组(P0.05)。研究组EDSS部分子项目评分变化及功能恢复均明显优于对照组(P0.05)。研究组用药后未出现严重不良反应。随访1a,研究组复发率明显低于对照组。结论利妥昔单抗联合激素冲击治疗视神经脊髓炎效果显著,明显改善患者视力及神经功能,降低致残率,提高日常生活能力,且安全有效,显著降低复发率。     

利妥昔单抗治疗重症肌无力的临床疗效分析

目的评价利妥昔单抗治疗重症肌无力(MG)的有效性和安全性。方法回顾性收集2018年2月至2019年7月北京医院神经内科收治的MG患者21例,所有患者血清抗乙酰胆碱受体(acetylcholine receptor,AChR)抗体或抗肌肉特异性酪氨酸激酶(muscle specific kinase,MuSK)抗体阳性。给予患者4次500mg利妥昔单抗治疗。分析患者治疗前后许氏评分,血CD19阳性B淋巴细胞、CD20阳性B淋巴细胞百分数以及相关抗体变化情况,同时观察利妥昔单抗的不良反应。结果共20例患者在使用4次500mg利妥昔单抗治疗后复查许氏评分,治疗前基线许氏评分为7~44分,平均(18.5±10.56)分,治疗后许氏评分为0~25分,平均(10.45±7.70)分,经利妥昔单抗治疗后患者许氏评分减低为6.5(3.25,12.75)分〔Md(P25,P75)〕,差异有统计学意义(P<0.01)。共16例患者于第1次、第2次、第3次及第4次利妥昔单抗用药后复查许氏评分,与用药前比较许氏评分降低分别为2(0,7)分〔Md(P25,P75)〕以及(6.12±4.54)、(6.18±5.98)、(8.12±5.80)分,与治疗前相比差异均有统计学意义(均P<0.01)。患者外周血CD19、CD20阳性B淋巴细胞计数于第一次用药后分别下降96%、97%。抗AChR抗体阳性患者共19例,用药后不同时间复查抗体水平14次,共发现2例患者抗体滴度降低。共9例患者出现不良反应,均为良性不良反应。结论4次500mg利妥昔单抗治疗MG显示出良好治疗效果,且安全性高,耐受性好。     

利妥昔单抗治疗难治性重症肌无力有效性和安全性的Meta分析

目的评价利妥昔单抗治疗难治性重症肌无力的有效性和安全性。方法以rituximab、myasthenia gravis等英文检索词计算机检索2000年1月1日-2018年4月30日美国国立医学图书馆生物医学信息检索系统(Pub Med)、荷兰医学文摘(EMBASE/SCOPUS)、Cochrane图书馆,并辅助手工检索获得回顾性病例分析和病例观察研究,采用Newcastle-Ottawa量表和Stata 12.0统计软件进行文献质量评价和Meta分析。结果共1772篇英文文献,经剔除重复和不符合纳入标准者,最终纳入11篇文献(包括回顾性病例分析10篇和病例观察研究1篇)共160例利妥昔单抗治疗的难治性重症肌无力患者[包括血清抗乙酰胆碱受体(ACh R)抗体阳性88例、抗肌肉特异性受体酪氨酸激酶(Mu SK)抗体阳性65例、抗ACh R和Mu SK抗体阴性7例]。Meta分析显示,利妥昔单抗治疗血清抗ACh R抗体阳性的难治性重症肌无力的临床症状改善率为77%(95%CI:0.642~0.899,P=0.030),治疗血清抗Mu SK抗体阳性或抗ACh R和Mu SK抗体阴性的难治性重症肌无力的临床症状改善率为73%(95%CI:0.631~0.829,P=0.048),且可以显著减少激素日剂量[治疗前31.80(20.00,45.90)mg/d、治疗后6.81(3.44,8.00)mg/d,减量21.70(15.50,42.46)mg/d;Z=2.366,P=0.018];利妥昔单抗不良反应主要包括白细胞减少症、阵发性心房颤动、感染性肺炎、进行性多灶性白质脑病、口腔带状疱疹等。结论循证医学方法对评价利妥昔单抗治疗难治性重症肌无力的有效性和安全性具有重要意义。利妥昔单抗治疗难治性重症肌无力安全、有效,并可以显著减少激素日剂量。     

利妥昔单抗治疗视神经脊髓炎谱系疾病的应用方案研究进展

视神经脊髓炎谱系疾病(NMOSD)是一种严重的中枢神经系统自身免疫性疾病,利妥昔单抗(RTX)可用于NM OSD缓解期的治疗.RTX是一种抗B淋巴细胞表面CD20的人-鼠嵌合单克隆抗体,通过剔除外周血中初始及记忆B淋巴细胞减少NMOSD的复发次数.目前有关RTX治疗NMOSD临床研究资料尚无统一的用药方案.现就RTX在...     

米托蒽醌治疗多发性硬化的疗效和安全性分析

目的探讨米托蒽醌治疗多发性硬化(MS)的疗效和副作用。方法回顾性分析应用米托蒽醌治疗的2例恶化的复发缓解型多发性硬化(WRRMS)和7例继发进展型多发性硬化(SPMS)的用药经过和临床情况,比较治疗前后年复发率(ARR)和测定临床神经功能缺损的扩充的残疾状态量表评分(EDSS)的差异,评价米托蒽醌的有效性和副作用。结果入组的9例患者平均接受米托蒽醌治疗6次,平均剂量(72.00±25.29)mg/m2,平均随访时间为(31.03±20.81)m,EDSS和ARR在治疗前后有显著性差异;用药后随访期间ARR与用药期间ARR相比无统计学差异,但随访结束时EDSS与用药期间相比有统计学差异,提示病情恶化。随访期间有2例患者后续治疗为吗替麦考酚酯,随访结束时2例患者没有复发,EDSS评分维持在用药结束时的状态。其余患者有4例在随访期间复发。米托蒽醌常见的副作用包括胃肠道反应、脱发、外周血白细胞下降、感染、肝功能异常和月经紊乱,未发现有心脏收缩功能减退和(或)心功能衰竭以及治疗相关白血病的发生。结论米托蒽醌治疗相对安全,疗效确切,2 y疗程结束后应继续其它免疫调节治疗,应予以推广应用于恶化的RRMS和SPMS。     

Effectiveness of low dose of rituximab compared with azathioprine in Chinese patients with neuromyelitis optica: an over 2-year follow-up study

Neuromyelitis optical (NMO) and neuromyelitis optical spectrum disorder (NMOSD) are inflammatory autoimmune demyelination diseases affecting the central nervous system. We investigated the efficiency of low-dose rituximab treatment in 31 Chinese patients with NMO/NMOSD across a median period of 2.29 ± 0.97 years and azathioprine combined with corticosteroid treatment in 34 Chinese patients with NMO/NMOSD across a median period of 2.61 ± 0.94 years. Among the rituximab-treated patients, the mean Expanded Disability Status Scale (EDSS) was 5.62 ± 1.35 before treatment and 4.48 ± 0.78 at last follow-up, and the mean annualized relapse rate (ARR) was 1.39 ± 0.42 before treatment and 0.03 ± 0.13 at last follow-up. Among the azathioprine-treated patients, the mean EDSS was 5.63 ± 1.29 before treatment and 5.05 ± 1.00 at last follow-up, and the mean ARR was 1.28 ± 0.34 before treatment and 0.49 ± 0.21 at last follow-up. In this study, we showed that using low-dosage rituximab could benefit Chinese patients with NMO by reducing the new occurrence of relapses dramatically. Compared with the azathioprine-treated patients, we concluded that rituximab is more effective in preventing NMO relapse and could improve the symptoms.     

脑脊液MOG抗体阳性的视神经脊髓炎谱系疾病患者的临床特征

目的探讨MOG抗体阳性的NMOSD患者的临床特点。方法选择29例NMOSD患者,根据血清AQP-4抗体以及脑脊液MOG抗体检测结果,分为MOG抗体阳性、AQP4抗体阳性的NMOSD(剔除双阳性者),同时选择13例MS患者作为对照。回顾性分析上述三组患者临床信息,统计归纳其临床特点。结果 29例NMOSD患者中血清AQP4抗体阳性者11例,脑脊液MOG抗体阳性者8例。36.4%(4例/11例)AQP4抗体阳性、62.5%(5例/8例)MOG抗体阳性NMOSD患者,以及7.7%(1例/13例)MS患者合并脊髓炎与视神经炎,三组间差异有统计学意义(χ~2=7.128,P=0.028),其中MOG抗体阳性NMOSD患者较MS患者更易合并视神经炎(χ~2=7.289,P=0.014)。MOG抗体阳性NMOSD患者缓解期EDSS分数低于AQP4抗体阳性NMOSD患者[3.50(2.50,4.00),4.00(3.50,6.00),Z=-2.379,P=0.020]。MOG抗体阳性NMOSD脊髓病灶多表现为多发的长节段脊髓病灶,50%(4例/8例)MOG抗体阳性脊髓病灶个数大于1个,与MS组无明显差异,而AQP4抗体阳性组均为单个病灶。MOG抗体阳性NMOSD脊髓病灶长度较AQP4抗体阳性组短[分别(3(2,3)个椎体、4(3,5)个椎体,Z=-2.499,P=0.012],较MS组[(1.25(1,1.5)个椎体]长(Z=-3.447,P0.001)。8例MOG抗体阳性患者中5例存在颅内病灶,3例表现为NMOSD样颅内病灶,余2例表现为MS样颅内病灶,其病灶形态及部位与AQP4抗体阳性组无明显差异,而与MS组存在差异。结论 MOG抗体阳性NMOSD合并视神经炎的患者较多,临床残障程度较轻,预后较好,脊髓病灶为多发的长节段脊髓病灶;颅内病灶的形态及部位与MS无明显差异。     

视神经脊髓炎谱系疾病在长期免疫抑制治疗前的病程特点及预后分析

目的了解中国视神经脊髓炎谱系疾病(NMOSD)患者有效免疫抑制治疗前的病程特点和预后。方法对122例中国NMOSD患者的首次发病症状、复发情况和神经功能障碍情况进行回顾性分析,应用KaplanMeier方法分析预后。结果 122例NMOSD患者(女性占86%)的首次发病症状,41例有视神经炎表现,43例累及脊髓,41例累及延髓最后区,累及脑部其他位置的15例,视神经和脊髓同时受累的仅2例。122例中116例(95%)病程中有复发,78例(67%)在发病1年内、94例(77%)在发病2年内复发,年复发率中位数(最小值~最大值)1.30(0.05~10.00)次/年。首次发作后,3个月后恢复期扩展残疾状态量表(EDSS)评分中位数(最小值~最大值)为0(0~7),仅6例(5%)不能独立行走(EDSS评分≥6);第2次临床发作后恢复期,99例(81%)无或仅有很轻微神经功能障碍(EDSS评分≤3),8例(7%)EDSS评分≥6。预后分析结果显示发病10年后约20%患者不能独立行走,25%至少单眼盲。结论此组中国NMOSD绝大多数呈复发性病程,虽有较明显的致残性,但前两次发作后仅有小部分患者遗留神经功能障碍。     

Demographic and clinic characteristics of French patients treated with natalizumab in clinical practice

Natalizumab is the first selective adhesion molecule inhibitor indicated for treatment of active relapsing-remitting multiple sclerosis (RRMS). Natalizumab has been available in France since April 2007. The aims of this study are to analyze demographic, clinical, and tolerance data from French patients with RRMS treated with natalizumab in actual clinical practice and to draw comparisons with patients in the pivotal AFFIRM study. All patients with RRMS in the Nord-Pas de Calais and Alsace regions of France treated with natalizumab at any time since April 2007 were included. Variables analyzed included previous treatments; disability status [Expanded Disability Status Scale (EDSS) score]; annualized relapse rate (ARR) at baseline and after 12 months of treatment; and adverse events. Data from 384 patients (72% female) were evaluated. Mean baseline EDSS score was 3.53 and mean baseline ARR was 2.19, both significantly greater than in AFFIRM. One hundred twenty-seven patients completed 12 months of treatment; mean EDSS score in this group was 3.02 (14% reduction) and mean ARR was 0.59 (73% reduction). Although these patients had significantly different baseline characteristics and greater disability compared with patients receiving natalizumab in AFFIRM, average disability remained stable and ARR declined by 73%. Tolerability was similar to that observed in AFFIRM.     

The differential expression of natural killer cells in NMOSD and MS

Natural killer (NK) cells are involved in the pathogenesis of inflammatory demyelinating diseases of the central nervous system. However, the differential expressions of NK cells in the peripheral blood of patients with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are unknown. This study aimed to explore the differential expressions of NK cells in NMOSD and MS and evaluate the clinical implications of this difference. We performed a cross-sectional study to investigate the expression of NK cells in the peripheral blood of patients with NMOSD (n = 78) and MS (n = 24) and of healthy controls (HC, n = 27). Furthermore, we investigated the relationship between NK cell level and disease phase in 102 patients with NMOSD and MS through Spearman correlation analysis and receiver operating characteristic (ROC) analysis. Our results showed that the median (interquartile range) NK cell levels in acute-phase NMOSD patients, remission-phase NMOSD patients, acute-phase MS patients, and HC subjects were 114.10 (64.75–153.38) cells/µL, 167.60 (116.35–266.15) cells/µL, 282.55 (140.57–368.20) cells/µL, and 221.00 (170.40–269.55) cells/µL, respectively (p < 0.001). The Spearman correlation coefficient (95%) for the relationship between NK level and disease phase in NMOSD patients was 0.366 (0.150–0.550) (p < 0.001). Furthermore, ROC analysis revealed that patients with NK cell values lower than 172.200 cells/µL were more prone to have acute-phase NMOSD than MS. In conclusion, the expression of NK cells in peripheral blood was lower in patients with NMOSD than in patients with MS in the acute phase, and a low expression of NK cells may suggest having acute-phase NMOSD rather than MS.     

Disease Course and Outcomes in Patients With the Limited Form of Neuromyelitis Optica Spectrum Disorders and Negative AQP4-IgG Serology at Disease Onset: A Prospective Cohort Study

Background and PurposePatients presenting with clinical characteristics that are strongly suggestive of neuromyelitis optica spectrum disorders (NMOSD) have a high risk of developing definite NMOSD in the future. Little is known about the clinical course, treatment, and prognosis of these patients with likely NMOSD at disease onset.MethodsThis study prospectively recruited and visited 24 patients with the limited form of NMOSD (LF-NMOSD) at disease onset from November 2012 to June 2021. Their demographics, clinical course, longitudinal aquaporin-4 immunoglobulin G (AQP4-IgG) serology, MRI, therapeutic management, and outcome data were collected and analyzed.ResultsThe onset age of the cohort was 38.1±12.0 years (mean±standard deviation). The median disease duration was 73.5 months (interquartile range=44.3–117.0 months), and the follow-up period was 54.2±23.8 months. At the end of the last visit, the final diagnosis was categorized into AQP4-IgG-seronegative NMOSD (n=16, 66.7%), AQP4-IgG-seropositive NMOSD (n=7, 29.2%), or multiple sclerosis (n=1, 4.2%). Seven of the 24 patients (29.2%) experienced conversion to AQP4-IgG seropositivity, and the interval from onset to this serological conversion was 37.9±21.9 months. Isolated/mixed area postrema syndrome (APS) was the predominant onset phenotype (37.5%). The patients with isolated/mixed APS onset showed a predilection for conversion to AQP4-IgG seropositivity. All patients experienced a multiphasic disease course, with immunosuppressive therapy reducing the incidence rates of clinical relapse and residual functional disability.ConclusionsDefinite NMOSD may be preceded by LF-NMOSD, particularly isolated/mixed APS. Intensive long-term follow-up and attack-prevention immunotherapeutic management is recommended in patients with LF-NMOSD.     

甲泼尼龙冲击治疗对视神经脊髓炎谱系病患者外周血滤泡辅助性T细胞百分率的影响

目的探究视神经脊髓炎谱系病(NMOSD)患者外周血滤泡辅助性T细胞(Tfh)百分率在甲泼尼龙冲击治疗前、后的变化。方法收集AQP-4抗体阳性的急性期NMOSD患者(NMOSD组)23例,采用流式细胞术检测甲泼尼龙冲击前、后外周血CXCR5~+ICOS~+的CD4~+T细胞(Tfh细胞),记录NMOSD组的EDSS评分,分析NMOSD组患者Tfh细胞百分率与患者AQP-4抗体滴度及EDSS评分的相关性。结果 NMOSD组患者甲泼尼龙冲击治疗前外周血Tfh细胞百分率[(1.77±0.74)%]显著高于甲泼尼龙冲击治疗后[(1.26±0.45)%](t=2.284,P=0.032)。首次发病NMOSD患者甲泼尼龙冲击治疗前Tfh细胞百分率与EDSS评分呈正相关(r=0.625,P=0.040),甲泼尼龙冲击治疗前、后Tfh细胞百分率与AQP-4抗体滴度无相关性(r=--0.02,P=0.928)。结论经甲泼尼龙冲击治疗后,NMOSD患者急性期外周血Tfh细胞百分率降低,首次发病NMOSD患者Tfh细胞百分率水平与EDSS评分有关。Tfh细胞百分率水平可能与NMOSD的复发有关。     

High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis

BACKGROUND: High-dose cyclophosphamide is active in immune-mediated illnesses. OBJECTIVE: To describe the effects of high-dose cyclophosphamide on severe refractory multiple sclerosis. DESIGN, SETTING, AND PATIENTS: Patients with multiple sclerosis with an Expanded Disability Status Scale (EDSS) score of 3.5 or higher after 2 or more Food and Drug Administration-approved disease-modifying therapy regimens were evaluated. INTERVENTIONS: Patients received 200 mg/kg of cyclophosphamide over 4 days. MAIN OUTCOME MEASURES: Patients had brain magnetic resonance imaging and neuro-ophthalmologic evaluations every 6 months and quarterly EDSS and quality-of-life evaluations for 2 years. RESULTS: Twelve patients were evaluated for clinical response (median follow-up, 15.0 months; follow-up range, 6-24 months). During follow-up, no patients increased their baseline EDSS scores by more than 1.0. Five patients decreased their EDSS scores by 1.0 or more (EDSS score decrease range, 1.0-5.0). Two of 11 patients had a single enhancing lesion at baseline; these lesions resolved after high-dose cyclophosphamide treatment. At 12 months, 1 patient showed 1 new enhancing lesion without a corresponding high-intensity T2-weighted or fluid-attenuated inversion recovery signal. Patients reported improvement in all of the quality-of-life parameters measured. Neurologic improvement involved changes in gait, bladder control, and visual function. Treatment response was seen regardless of the baseline presence or absence of contrast lesion activity. Patient quality-of-life improvement occurred independently of EDSS score changes. In this small group of patients with treatment-refractory multiple sclerosis, high-dose cyclophosphamide was associated with minimal morbidity and improved clinical outcomes. CONCLUSIONS: High-dose cyclophosphamide treatment in patients with severe refractory multiple sclerosis can result in disease stabilization, improved functionality, and improved quality of life. Further studies are necessary to determine the most appropriate patients for this treatment.     

光相干连续断层成像术在视神经脊髓炎谱系病的临床应用

目的探讨光相干连续断层成像术(OCT)在视神经脊髓炎谱系病(NMOSD)的临床应用。方法利用OCT对49例NMOSD患者(NMOSD组)和1 5例健康对照志愿者(对照组)视乳头周围视网膜神经纤维层(RNFL)厚度进行比较;NMOSD组再根据是否伴视神经炎、水通道蛋白抗体状态(AQP4-IgG)等对NMOSD组分为伴视神经炎(NMOSD-ON)亚组(34例);不伴视神经炎(NMOSD-NON)亚组(15例)。比较各亚组的RNFL厚度差异;采用扩展病残状态评分(EDSS)评价神经功能缺损程度,分析EDSS与RNFL是否存在相关性。结果 NMOSD患者受累眼的RNFL各象限厚度与未受累眼和对照组比较显著变薄(P0.01);NMOSD未受累眼与对照组比较,RNFL厚度差异无显著性(P0.05)。AQP4-IgG阳性或阴性NMOSD-ON亚组的RNFL厚度比较差异无显著性(P0.05);RNFL厚度变化与NMOSD残障的严重程度无相关性(P0.05)。结论 RNFL变薄仅在NMOSD受累眼表现,厚度变化与AQP4-IgG无关,OCT可能有助于临床对NMOSD诊疗提供参考指标。     

Efficacy and safety of different dosages of rituximab for refractory generalized AChR myasthenia gravis: A meta-analysis

BackgroundRituximab (RTX) is a mouse-human chimeric anti-CD20 monoclonal antibody and has been increasingly used for preventing relapses in myasthenia gravis (MG). However, the appropriate dose for maximizing the beneficial effects in refractory MG with acetylcholine receptor (AChR) autoantibody is a long-standing and critical debating question.MethodsWe performed a meta-analysis to evaluate the efficacy and safety of the different doses of RTX in 260 refractory AChR-MG patients.ResultsThe AChR-MG patients were divided into low or routine RTX dose groups. An overall proportion of 77% (p = 0.000) AChR-MG patients demonstrated improved clinical status as indicated by the Myasthenia Gravis Foundation of America post-intervention scale (MGFA-PIS). There were 77.1% patients showed improved clinical status in lower dose of RTX group (p = 0.000) and 76.8% in routine protocol group (p = 0.000). Although we found there was no significant difference in the proportion of AChR-MG patients with improved clinical status or adverse reactions between the two groups, adverse reactions might be lower in the lower dose RTX group.ConclusionMost of refractory MG patients with anti-AChR autoantibody were well responsive and tolerated to RTX treatment. Repeated application of lower dose of RTX was effective and might be more appropriate for refractory AChR-MG patients with potential lower side effects.