【作者】 韩冰；

【导师】 刘晶瑶；

【作者基本信息】 吉林大学 ， 临床医学硕士（神经病学）（专业学位）， 2019， 硕士

【摘要】 目的:回顾性分析视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disease,NMOSD)与多发性硬化(multiple sclerosis,MS)的一般临床资料、实验室检查及影像学改变,总结其临床特征点,为今后二者的早期诊断及鉴别诊断提供参考。探讨NMOSD合并系统性自身免疫病(systemic autoimmune diseases,SADs)与不合并 SADs 患者在一般临床特点以及实验室检查等方面的差异,以利于更好的诊断与治疗。方法:本研究将以2013-2018年至我院住院患者作为研究对象,根据2015年国际视神经脊髓炎诊断小组(Intemationai Panel for NMO Diagnosis,IPND)提出的NMOSD新的诊断标准和2017年McDonald MS诊断标准进行筛选分组,分为NMOSD组和MS组,其中又将NMOSD组中是否合并SADs分成两组。将患者一般临床资料、实验室检查、影像学资料等进行对比,并通过统计学方法研究NMOSD及MS患者临床特点之间存在的差异和NMOSD患者中合并SADs者的一般临床特点。结果:1、NMOSD与MS男女比例分别为2/29和17/26,两组间差异有统计学意义(x^10.331,P=0.01)。NMOSD平均起病年龄42.33±10.39岁,MS平均起病年龄为30.74±7.06岁,NMOSD发病年龄比MS晚,两组间差异有统计学意义(x2=5.716,P=0.000)。在年龄分布上两组无明显差异(P>0.05)。NMOSD的首发症状中,表现为膀胱直肠症状8例(25.8%),表现为吞咽困难症状有5例(16.1%),均高于MS首发症状的ON 16例(37.2%),膀胱直肠症状2例(4.7%),吞咽困难0例,差异有统计学意义(P<0.05)。对于首发症状为四肢无力的患者,NMOSD临床表现为截瘫16例(66.7%),四肢瘫4例(16.7%),偏瘫1例(4.2%),单瘫3例(12.5%)。MS中截瘫8例(30.8%),单瘫 11 例(42.3%),偏瘫 4 例(15.4%),四肢瘫 3 例(11.5%)。NMOSD的截瘫发生率高于MS,两组间差异有统计学意义(x2=6.443,P=0.011)。MS的单瘫患者例数明显高于NMOSD,两组间差异有统计学意义(x2=5.500,P=0.019)。在首发症状为感觉障碍患者中,感觉异常NMOSD有11例(73.3%),MS有17例(77.3%));感觉减退NMOSD有12例(80%),MS有13例(59.1%),上述两种疾病常见的症状比较两组间无统计学差异(P>0.05)。NMOSD组发生深感觉障碍有9例(60%),高于MS的6例(27.3%),两组差异有统计学意义(x2=3.963,P=0.047)。NMOSD脑脊液实验室检查中,12例(38.7%)患者白细胞升高,高于MS的7例(16.3%),差异有统计学意义(x2=4.749,P=0.029)。MS组中发生IgG指数升高及寡克隆区带(Oligo clonalabands,OCB)阳性的有 21 例(48.8%)和 28 例(65.1%),高于NMOSD的2例(6.5%)和1例(3.2%),差异存在统计学意义(P<0.05)。脑脊液压力和蛋白改变没有统计学意义(P>0.05)。NMOSD组的抗核抗体系列阳性有26例(83.9%),甲状腺相关抗体阳性13例(41.9%),AQP4抗体阳性有29例(93.5%),均高于MS组,两组间存在统计学差异(P<0.05)。磁共振检查中,NMOSD组患者中脊髓有病灶的有24例(77.4%),发生脊髓长节段病灶(longitudinally extensive cord lesions,LDSCLs)的有 22 例(71.0%),高于 MS 的 23例(53.5%)和4例(9.3%),差异存在统计学意义(P<0.05)。MS的颅内病灶的发生率高于NMOSD,两组间存在统计学差异(x2=4.841,P=0.028)。2、NMOSD-SADs组与NMOSD-非SADs组的首发临床表现中,NMOSD-SADs 组发生 ON 的有 6 例(75%),高于 NMOSD-非 SADs组的6例(26.1%),两组差异有统计学意义(x2=4.101,P=0.043)。NMOSD组发生延髓最后区综合征的有1例(12.5%),NMOSD-非SADs组未发现有延髓最后区综合征的患者,二者间存在统计学差异(x2=5.625,P=0.018)。余临床表现未见明显差别(P>0.05)。NMOSD-SADs组中甲状腺球抗体、抗核抗体、抗SSA、抗SSB阳性率显著高于NMOSD-非SADs组(P<0.05)。结论:NMOSD与MS是两种完全独立的疾病,虽然有相似之处,但流行病学、临床特点、实验室及影像学均有不同之处,临床中应注意早期鉴别。NMOSD合并SADs的患者更容易以ON为首发症状起病,且血清自身抗体阳性率高于不伴有SADs的患者,因此,对于以ON起病的NMOSD和自身抗体阳性的NMOSD更应注意是否合并有SADS。更多还原

【Abstract】 Objective:Neuroomyelitis optica spectrum disease(NMOSD)and multiple sclerosis(MSTo explore the differences in general clinical characteristics and laboratory examinations between patients with and without SADs of NMOSD combined with systemic autoimmune diseases(SADs),so as to facilitate better diagnosis and treatment.Methods:Patients admitted to our hospital from 2013 to 2018 were selected as subjects in this study.According to the 2015 international Panel for NMO Diagnosis(IPND),the new diagnostic criteria for NMOSD and the 2017 McDonald MS diagnostic criteria,the patients were divided into NMOSD group and MS group.The general clinical data,laboratory examination and laboratory characteristics of imaging data of patients were compared,and the differences between the clinical characteristics of NMOSD and MS patients and the general clinical characteristics of patients with SADs in NMOSD patients were studied by statistical methods.Results:1.The male/female ratio of NMOSD and MS was 2/29 and 17/26,respectively,and the difference between the two groups was statistically significant(=10.331,P=0.01).The mean age of onset of NMOSD was 42.33 10.39 years,and the mean age of onset of MS was 30.74 7.06 years.The age of onset of NMOSD was later than that of MS,and the difference between the two groups was statistically significant(=5.716,P=0.000).There was no significant difference between the two groups(P>0.05).Bladder and rectum in 8 cases(25.8%),dysphagia in 5 cases(16.1%),which was higher than that in 16 cases(37.2%),bladder and rectum in 2 cases(4.7%),and dysphagia in 0 cases(P<0.05).For patients with the first symptom of limb weakness,the clinical manifestations of NMOSD were paraplegia in 16 cases(66.7%),tetraplegia in 4 cases(16.7%),hemiplegia in 1 case(4.2%),and monoplegia in 3 cases(12.5%).There were 8 cases of paraplegia(30.8%),11 cases of monoplegia(42.3%),4 cases of hemiplegia(15.4%)and 3 cases of tetraplegia(11.5%)in MS.The incidence of paraplegia in NMOSD was higher than that in MS,and the difference between the two groups was statistically significant(=6.443,P=0.011).The number of patients with MS was significantly higher than that of NMOSD,and the difference between the two groups was statistically significant(=5.500,P=0.019).Among the patients with the first symptom of sensory disturbance,11 cases(73.3%)had paresthesia in NMOSD and 17 cases(77.3%)in MS.There were 12 NMOSD(80%)and 13 MSS(59.1%).The results showed that there was no statistical difference between the two groups(P>0.05).In the NMOSD group,there were 9 cases(60%)of deep sensory disturbance,higher than the 6 cases(27.3%)of MS.The difference between the two groups was statistically significant(=3.963,P=0.047).In the laboratory examination of NMOSD cerebrospinal fluid,12 patients(38.7%)had elevated WBC,which was higher than that of 7 patients(16.3%)with MS,and the difference was statistically significant(=4.749,P=0.029).In MS group,there were 21 cases(48.8%)and 28 cases(65.1%)with positive Oligo clonala bands(OCB),which were higher than 2 cases(6.5%)and 1 case(3.2%)of NMOSD(P<0.05).The changes of cerebrospinal fluid pressure and protein concentration showed no statistical significance(P>0.05).There were 26(83.9)positive antinuclear antibody series in the NMOSD group,13(41.9%)positive thyroid related antibody series,and 29(93.5%)positive AQP4 antibody series in the NMOSD group,all higher than that in the MS group.The difference between the two groups was statistically significant(P<0.05).Magnetic resonance imaging,NMOSD group of patients with lesions of the spinal cord has 24 cases(77.4%),occurred long segmental spinal cord lesions(longitudinally extensive cord lesions,LDSCLs)of 22 cases(71.0%),higher than that of MS 23 cases(53.5%)and 4 cases(9.3%),the difference has statistical significance(P<0.05).The incidence of intracranial lesions of MS was higher than that of NMOSD,and the difference between the two groups was statistically significant(=4.841,P=0.028).2.Among the first clinical manifestations of nmosd-sads group and nmosd-non-sads group,there were 6 cases(75%)of ON in the nmosd-sads group,which was higher than that in the nmosd-non-sads group(26.1%).The difference between the two groups was statistically significant(=4.101,P＝0.043).In the NMOSD group,there was 1 case(12.5%)of bulbar last area syndrome,while in the NMOSD-non-sads group,there was no significant difference between the two groups(=5.625,P=0.018).The rest showed no obvious difference(P>0.05).The positive rates of thyroid ball antibody,anti-nuclear antibody,anti-ssa and anti-ssb in the nmosd-sads group were significantly higher than those in the nmosd-sads group(P<0.05).Conclusions:NMOSD and MS are two completely independent diseases.Although there are some similarities,there are differences in epidemiology,clinical characteristics,laboratory and imaging.Early identification should be paid attention to in clinical practice.Patients with NMOSD combined with SADs are more likely to start with ON as the first symptom,and the positive rate of serum autoantibodies is higher than that of patients without SADs.Therefore,more attention should be paid to whether there are SADs in the combination of NMOSD with ON and NMOSD with positive autoantibodies.更多还原