副瘤性神经系统综合征的常见临床类型与免疫学研究

Clinical types and immunological study in patients with paraneoplastic neurological syndrome

目的:探讨副瘤性神经系统综合征(paraneoplastic neurological syndrome, PNS)常见临床类型、相关肿瘤及特异性神经元抗体的临床意义。方法:采用Graus和Delattre制定的国际PNS诊断标准,回顾性分析了75例PNS患者常见临床类型和相关肿瘤,用间接免疫荧光法、亲和免疫细胞组织化学法及蛋白质印迹技术检测患者血中的特异性神经元抗体。结果:75例患者中小细胞肺癌(small cell lung cancer,SCLC)51例(68.0%),卵巢癌6例,恶性淋巴瘤3例,肺鳞癌、乳腺癌、食管癌各2例,肺腺癌、宫颈癌、多发性骨髓瘤、前列腺癌、胃癌、贲门癌、结肠癌、肝癌、大单核细胞白血病各1例,其中副瘤性周围神经病48例(64.0%)、副瘤性脑脊髓炎11例(14.7%)、副瘤性小脑变性11例(14.7%)、副瘤性边缘叶脑炎3例、郎伯综合征(Lambert-Eaton综合征) 2例。特异性神经元抗体阳性31例,其中抗-Hu抗体阳性18例,抗-Yo抗体阳性7例,抗-Ma2抗体阳性4例,抗CV2抗体阳性、抗神经突胆触囊泡抗体阳性各1例。结论:在PNS患者中密切相关肿瘤是SCLC和妇科肿瘤,最常见的临床类型是副瘤性周围神经病,其次是副瘤性脑脊髓炎及副瘤性小脑变性,特异性神经元抗体的常见类型主要是抗Hu抗体、抗Ma2抗体及抗Yo抗体,抗体检测对于PNS的早期诊断具有重要临床意义。

Objective To study the clinical types, related tumors and expressing of specific anti-neuronal antibodies in patients with paraneoplastic neurological syndrome （PNS）. Methods According to the international diagnostic criteria for PNS recommended by Graus and Delattre, 75 PNS patients were diagnosed and their clinical types and related tumors were analyzed retrospectively. Indirect immunofluorescence, immunohistochemistry and Western blotting were used to identify the specific anti-neuronal antibodies （including anti-Hu, anti-Yo, anti-Ri, anti-CV2, anti-Ma2 and anti-amphiphysin） in serum of 75 PNS patients. Results In 51 （68.0%） patients the associated tumor was small cell lung cancer （SCLC）. Oth- er tumors were： 6 ovarian cancer, 3 malignant lymphoma, 2 squamous cell lung carcinoma, 2 breast cancer, 2 esophagus cancer, 1 adenoearcinolna of lung, 1 cervical cancer, 1 muhiple myeloma, 1 prostate cancer, 1 gastric carcinoma, 1 car- diac carcinoma,1 colon cancer, l liver cancer and 1 large monocytic leukemia. In 75 PNS patients, there were 48 （64.0%） paraneoplastic peripheral neuropathy （PPN）, 11 （14.7%） paraneoplastic encephalomyelitis （PEM） and ll （14.7%） paraneo- plastic cerebellar degeneration （PCD）, 3 paraneoplastic limbic encephalitis （PLE）, 2 Lambert-Eaton myas-thenic syndrome （LEMS）. The specific neuronal antibodies in serum identified in 31 patients were： anti-Hu antibody in 18 patients, anti-Yo in 7 patients, anti-Ma2 antibody in 4 patients, anti-CV2 in 1 patient and anti-amphiphysin in 1 patient. Conclusions SCLC and gynecological cancer were tumors closely associated with PNS. The predominant PNS were PPN, PEM and PCD. Study of specific neuronal antibodies was helpful to correctly identify particular PNS.