原发性干燥综合征合并中枢神经系统病变38例临床分析

Central nervous system involvement in primary Sjogren＇s syndrome： a study of 38 patients

目的探讨pSS合并中枢神经系统（CNS）病变的临床特点，以提高对该病的诊疗水平。方法总结2012-2016年于我院确诊pSS-CNS病变的38例患者的临床资料，按EULAR SS疾病活动指数（ESSDAI）评分，将CNS病变分为高度活动组及中度活动组，进行回顾性对比分析。计数资料比较采用χ^2检验或Fisher确切概率法检验，计量资料比较采用t检验。结果① pSS患者CNS病变发生率2.93%（38/1 296），以CNS病变为首发表现的有32%（12/38），复发率39%（15/38）；② pSS患者的CNS病变最常见为肢体无力、语言障碍、感觉障碍、视力减退等，影像学为多灶性病变，16例患者中94%（15/16）存在脑脊液指标异常，其中脑脊液中免疫球蛋白（Ig）G升高达50%（8/16），此外，CNS病变高度活动组与中度活动组相比，患者肺部受累、血小板减少、高滴度ANA（1∶1 000）阳性率升高，差异有统计学意义（χ^2值分别为4.7、5.0、5.3，P值均〈0.05）；③ 61%（23/38）患者经过大剂量甲泼尼龙及免疫治疗好转或缓解，37%（14/38）无效，3%（1/38）死亡，对治疗无效的患者予间充质干细胞移植或免疫吸附治疗有一定疗效。结论① pSS-CNS病变临床表现多样，部分以CNS病变为首发，发病率低，复发率高；②影像学及脑脊液检测对诊断具有重要意义；③肺部受累、血小板减少、高滴度ANA与CNS病变活动度有关；④大部分患者对大剂量激素及免疫抑制治疗有效，对于治疗无效的患者可考虑间充质干细胞移植或免疫吸附治疗。

ObjectiveTo analyze the clinical profile of primary Sjogren′s syndrome （pSS） patients with central nervous system （CNS） involvement.MethodsThirty-eight pSS-CNS patients at Nanjing Drum Tower Hospital between 2012 and 2016 were enrolled. These patients were divided into high activity group and moderate activity group, according to European League against Rheumatism Sj？gren′s syndrome Disease Acti-vity Index （ESSDAI）. The imaging characteristics, clinical features, laboratory examinations and treatment of 38 cases were retrospectively analyzed. Quantitative differences were analyzed by the student＇s t-test and qualit-ative data were analyzed with chi-square or Fisher＇s exact test.ResultsThe prevalence of central nervous system involvement in pSS patients was 2.93%（38/1 296）, while 32%（12/38） as the initial symptom of pSS. Recurrence rate was 39%（15/38）. Limb weakness, speech difficulty, sensory disorders, blurred visionwere the most frequent symptoms in pSS-CNS. Multiple lesions in Magnetic resonance imaging （MRI） examination and cerebrospinal fluid abnormality were seen in 94% （15/16） pSS-CNS patients, among which intra-thecal IgG level increased in 50%（8/16）. In addition, the frequencies of lung involvement, immune associated thrombocytopenia, high-titer antinuclear antibody （ANA） were significantly higher in high activity group of pSS-CNS than those of moderate activity group. The value of above items was 4.7, 5.0 and 5.3, respectively, and all the differences were significant （P〈0.05）.After high-dose corticosteroids and immunosuppressive therapy, 61%（23/38） patient improved, 37%（14/38） were unresponsive to treatment, and 3%（1/38） died because of acute massive cerebral infarction. For those unresponsive patients, mesenchymal stem cell transplantation or immune adsorption treatment might be effective.ConclusionThe clinical manifestations of central nervous system are diverse, may be the initial presentations in some pSS patients, with low morbidity and high recurrence rate. Image and lumbar puncture are important for diagnosis. Pulmonary involvement, immune thrombocyto-penia, and high-titer ANA are frequently associated with the activity of pSS-CNS. Most patients have good response to the treatment regimens of high-dose corticosteroids and immunosuppressive therapy, mesenchymal stem cell transplantation or immuno-sorption therapy may be considered in those unresponsive cases.