Cross Shelley A, Salomao Diva R, Parisi Joseph E, Kryzer Thomas J, Bradley Elizabeth A, Mines Jonathan A, Lam Byron L, Lennon Vanda A
Department of Neurology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.
Ann Neurol. 2003 Jul;54(1):38-50. doi: 10.1002/ana.10587.
Autoantibodies have defined two paraneoplastic visual disorders related to small-cell lung carcinoma: retinopathy ("CAR"-IgG [23kDa, recoverin]) and optic neuritis collapsin response-mediated protein 5 (CRMP-5-IgG [62kDa]). Among 16 patients with CRMP-5-IgG and optic neuritis (aged 52-74 years; all smokers, 9 women), we documented coexisting retinitis in 5. None had CAR-IgG. Fifteen had subacute vision loss, swollen optic discs, and field defects. Vascular leakage was evident at and remote from the disc; 5/5 tested had abnormal electroretinograms. Nine had striking vitreous cells. Vitrectomy showed reactive lymphocytosis (4/4), predominantly CD4(+) (1/1). Most patients had multifocal neurological accompaniments. Cerebrospinal fluid contained lymphocytes (7-32), elevated protein, multiple oligoclonal immunoglobulin bands, and CRMP-5-IgG. Three patients superficially resembled Devic's disease at presentation. One autopsied patient had predominantly CD8(+) T lymphocytes infiltrating optic nerve and spinal cord. Eleven patients had confirmed small-cell carcinoma; 1 had imaging evidence of lung cancer; 3 had renal or thyroid carcinoma. Full-length CRMP-5 protein was identified in normal retina and optic nerve by Western blot analyses. Photoreceptor cells, retinal ganglion cells, and nerve fibers exhibited CRMP-5-specific immunoreactivity. In summary, CRMP-5-IgG defines a paraneoplastic ophthalmological entity of combined optic neuritis and retinitis with vitreous inflammatory cells. Positive serology obviates the need for vitreous biopsy and expedites the search for cancer.
视网膜病变（“CAR”-IgG [23kDa， recoverin]）和视神经炎（塌陷反应介导蛋白5（CRMP-5-IgG [62kDa]））。在16例患有CRMP-5-IgG和视神经炎的患者中（年龄52 - 74岁；均为吸烟者，9名女性），我们记录到5例同时存在视网膜炎。均无CAR-IgG。15例有亚急性视力丧失、视盘肿胀和视野缺损。视盘处及远离视盘处均有明显的血管渗漏；5例接受检测的患者视网膜电图均异常。9例有明显的玻璃体细胞。玻璃体切除术显示反应性淋巴细胞增多（4/4），主要为CD4(+)（1/1）。大多数患者有多处神经系统伴随症状。脑脊液中含有淋巴细胞（7 - 32个）、蛋白升高、多条寡克隆免疫球蛋白带和CRMP-5-IgG。3例患者初诊时表面上类似Devic病。1例尸检患者的视神经和脊髓主要有CD8(+) T淋巴细胞浸润。11例患者确诊为小细胞癌；1例有肺癌的影像学证据；3例有肾癌或甲状腺癌。通过蛋白质印迹分析在正常视网膜和视神经中鉴定出全长CRMP-5蛋白。光感受器细胞、视网膜神经节细胞和神经纤维表现出CRMP-5特异性免疫反应性。总之，CRMP-5-IgG定义了一种伴有玻璃体炎性细胞的视神经炎和视网膜炎合并的副肿瘤性眼科疾病实体。血清学阳性无需进行玻璃体活检，并加快了癌症的排查。
