重型神经精神性狼疮患者的临床表现及影像学改变

Clinical manifestation and brain magnetic resonance imaging finding in 51 severe neuropsychiatric systemic lupus erythematosus

目的：探讨重型神经精神性狼疮（NPSLE）患者临床特点及预后，比较缓解组及未缓解组临床及实验室指标的差异。方法：选取2006年12月至2013年4月南京军区南京总医院全军肾脏病研究所收治的重型NPSLE患者51例，回顾性分析其临床表现、实验室检查结果、影像学特点、治疗及预后。结果：51例患者中女性42例、男性9例，平均年龄26.3±9.7岁（15～64岁）。10例为初发初治病例。脑病发作时系统性红斑狼疮活动性指数（SLE-DAI）为20.3±7.0分（8～36分）。51例患者共发生101例次神经精神事件，中枢神经系统事件92例次（91.1％），周围神经系统事件9例次（8.9％）。最常见症状分别为癫痫发作（43.1％）、顽固性头痛（33.3％）、急性精神错乱（33.3％）和脑血管病（21.6％）。90％患者头颅MRI检查异常，以多发异常信号（38％）和脑梗塞（34％）最常见。尿蛋白定量中位数为2.65g／d（0.21～10.05g／d）、血清肌酐212.2±176.8Iμmol／L（40.7～832.7μmol／L）。患者免疫学指标异常突出，抗核抗体（ANA）、抗双链DNA（ds.DNA）和抗C1q抗体的阳性率分别为94.1％、54.9％、65.8％，抗心磷脂抗体和狼疮样抗凝物质的阳性率分别为42.6％和31.8％。30例（61.2％）患者存在低补体c3血症，17例（34.7％）存在低补体C4血症。血管细胞黏附分子和白细胞黏附功能异常的阳性率高达90.9％。诊断明确后予患者足量激素诱导治疗，其中32例（62.7％）予甲泼尼龙冲击治疗，其余治疗包括静脉注射丙种球蛋白、双重血浆滤过、血浆置换、免疫吸附和环磷酰胺、低分子肝素、抗血小板、抗癫痫等药物治疗，26例（50.9％）患者行连续性。肾脏替代治疗。46例（90.2％）患者经治疗后病情好转出院，3例（5.9％）患者因治疗后症状改善不明显放弃，2例（3.9％）患者死亡（1例临床诊断脑干梗塞，1例大面积出血性脑梗塞）。结论：本组重型NPSLE患者临床表现复杂多样，头颅MRI检查可见多种异常病变，SLE-DAI评分高，免疫学及内皮损伤指标明显异常。循环内皮细胞计数增高及颅内病变严重者预后不佳。

Objective：Neuropsychiatric （NP） involvement is severe manifestation of systemic lupus erythematosus （SLE）. The purpose of this study was to investigate the clinical feature and prognosis of SLE patients with severe NP events. Methodology：Fifty one SLE patients who had severe NP events in Jinling Hospital from 2006 to 2013 was retrospectively reviewed, satisfying the 1999 ACR criteria. Their clinical manifestations and brain magnetic resonance imaging findings were investigated. Results： They were 42 females and 9 males with an average age of 26. 3 ± 9. 7 years old （ range 15 ～ 64）. SLE disease activity index （SLEDAI） score was 20. 3 ± 7.0 （ range 8 ～ 36）. A total of 101 NP events were noticed in these patients,including 92 （91.1%） central nervous system events and 9 （8.9%） peripheral nervous system events. The most common manifestations were seizure disorder （43. 1% ）,followed by intractable headache （33.3% ）,acute confusional state （33.3%） and cerebrovascular disease （21.6%）. Abnormal brain MR/ features were detected in 90% of the patients, including multiple abnormal signals （38%） ,cerebral infarction （34%） and white matter lesions （20%）. The positive ratesof anti-nuclear antibodies （ANA）, anti-dsDNA antibodies, anti-Clq antibodies, anticardiolipin antibodies and lupus anticoagulant were 94. 1% ,54. 9% ,65. 8% ,40.4% and 27.9% respectively. The vascular cell adhesion molecule （VCAM） and leukocyte adhesion test were positive in 90. 9% of the patients. All patients were treated with prednisone. High dose intravenous methylprednisolone pulse therapy （0. 5g for 3 days） was administered to 32 （62. 7% ） patients. High dose intravenous immunoglobulin （ IVIG ）, double filtration plasmapheresis （ DFPP）, cyclophosphamide （ CYC ）, low molecular heparin and anti-platelet drugs were also applied. Forty-six patients （90. 2% ） had improvement and were discharged （remission group） ,2 （3.9%） died,3 （5.9%） patients gave up treatment （non-remission group）. The number of circulating endothelial cells （CECs） in non-remission group was significantly higher than in remission group （47. 8±19. 8 vs 28.5 ± 14.4 cells/ml, P= 0.014 ）. Conclusion： The clinical features of SLE patient with severe NP involvement were heterogeneous, manifested by high SLE-DAI scores and significant immune and endothelial abnormalities, as well as multiple abnormal brain MRI findings. Elevation of circulating endothelial cells may be a risk factor of vicious prognosis.