免疫介导坏死性肌病患者临床、股部磁共振及电生理特征分析

Retrospective study on clinical manifestation,thigh MRI and electrophysiology characteristics of immune-mediated necrotizing myopathy

目的总结归纳免疫介导坏死性肌病(IMNM)患者3个临床亚组的临床、股部磁共振(tMRI)及肌电图特点。方法纳入2019年4月至2021年4月解放军总医院第一医学中心神经内科确诊IMNM患者32例,分为抗信号识别颗粒抗体阳性(SRP^(+))组、抗3-羟基-3-甲基戊二酰辅酶A还原酶抗体阳性组(HMGCR^(+))和血清抗体阴性(SN)组,分析3组间的性别、年龄、病程、合并肌炎抗体、肌外表现、肌电图等临床资料,tMRI炎性水肿和脂肪浸润评分评估骨骼肌受累特征。应用方差分析、Kruskal-Wallis检验、Chi-square检验对比3组间不同临床特征以及tMRI评分的差异,3组间有统计学差异时,其中两组间比较应用Bonferroni法校正。结果(1)32例患者中女性20例(62.5%),起病年龄为18~76(47±14)岁,25例(78.1%)患者呈现急性或亚急性病程,SRP^(+)组17例(53.1%),HMGCR^(+)组8例(25.0%),SN组7例(21.9%)。抗Ro52抗体是最常见的合并抗体(12/32,37.5%),其中SRP^(+)组10例。(2)所有患者肌酸激酶值均升高,峰值中位数为5948(4229,7664)U/L,徒手肌力评定法(MMT)评分3组间差异无统计学意义(P值均>0.05),肢体近端低于远端(P<0.01),中轴肌低于肢体远端(P<0.05)。(3)HMGCR^(+)组肌外表现显著少于其余两组(12.5%比71.4%和76.5%,P<0.017),抗SRP抗体合并Ro52抗体阳性患者皮疹(60.0%比14.3%,P<0.05)和间质性肺病(70.0%比14.3%,P<0.05)均多于单纯SRP^(+)者。SN组合并结缔组织病最多见(57.1%比11.8%和0,P<0.017)。(4)tMRI示SN组的筋膜水肿比其他两组更明显(P<0.017),脂肪浸润和肌肉水肿程度在3组间差异无统计学意义(P值均>0.05),但SRP^(+)组有更多的病例早期即出现脂肪化。(5)HMGCR^(+)组中肌强直电位(25%比0和0,P<0.017)和复合重复放电(CRDs)(50.0%比5.9%和0,P<0.017)均明显多于其余两组,蛋白组学分析发现有上述自发电位患者的肌肉组织中细胞骨架、细胞连接和细胞外基质等相关蛋白表达上调。结论单纯SRP^(+)和HMGCR^(+)的IMNM以骨骼肌受累为主,抗SRP抗体和抗Ro52抗体共阳性者有更多的肌外表现,可能是SRP^(+)组的特殊亚型。本研究提出肌筋膜炎性水肿是SN-IMNM早期损伤征象。HMGCR^(+)组肌电图更易出现肌强直电位及CRDs。

Objective To summarize the clinical,thigh magnetic resonance(tMRI)and electromyographic(EMG)characteristics in patients with immune-mediated necrotizing myopathy(IMNM).Methods A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital.According to the type of antibody,the patients were divided into anti-SRP antibody positive(SRP^(+))group,anti-HMGCR antibody positive(HMGCR^(+))group and seronegative(SN)group.The gender,age,course of disease,myositis antibodies,extramuscular manifestations,EMG were collected and analyzed among three groups.The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores.Analysis of variance,Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups.When there was a statistical difference among the three groups,the comparison between the two groups was corrected by the Bonferroni method.Result(1)Of the 32 patients,20 were females(62.5%).The median age of onset was 47±14 years,25(78.1%)patients had an acute or subacute course.There were 17(53.1%)with SRP^(+),8(25.0%)with HMGCR^(+),and 7(21.9%)with MSAs(myositis specific antibodies)negative.Anti-Ro52 antibody was the most common combined antibody(12/32,37.5%),among which 10 were in SRP^(+)group.(2)The CK of all patients were elevated,median was 5948(4229,7664)U/L.There was no statistical difference of MMT scores among three groups.The proximal limb score was lower than distal limb(P<0.01).The axial muscle score was lower than the distal limb score(P<0.05).(3)Extramuscular manifestations of HMGCR^(+)group were lower than those of the other two groups(12.5%vs.71.4%and 76.5%,P<0.017).Rash(60.0%vs.14.3%,P<0.05)and interstitial pulmonary diseases(70.0%vs.14.3%,P<0.05)were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP.Connective tissue disease was more common in SN group(57.1%vs.11.8%and 0,P<0.017).(4)tMRI showed fascial edema of SN group was more obvious than that of the other two groups(P<0.017).There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups,but SRP^(+)group had more cases of early fat infiltration.(5)Myotonic potentials(25.0%vs.0 and 0,P<0.017)and compound repetitive discharges(CRDs)(50.0%vs.5.9%and 0,P<0.017)were common in HMGCR^(+)group.Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton,cell junction and extracellular matrix.Conclusion IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles.Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations,which might be a special subtype of SRP^(+)group.This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury.EMG of HMGCR^(+)group were more prone to myotonia potential and CRDs.