Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
Department of Ophthalmology, Shijiazhuang People's Hospital, Shijiazhuang 050011, China.
Dis Markers. 2022 Feb 17;2022:7076385. doi: 10.1155/2022/7076385. eCollection 2022.
To evaluate the value of serum and cerebrospinal fluid (CSF) testing in optic neuropathy (ON) patients with malignant tumors.
Fourteen patients clinically diagnosed as ON with malignant tumors but without intracranial or orbital mass in MRI were included in this study. Detailed medical records including medical history, complete ophthalmic examination, colour fundus photography, visual field test, orbital MRI examination, serum and CSF testing data were collected and analyzed. The diagnosis of paraneoplastic optic neuropathy (PON) based on the 2004 recommended criteria of the paraneoplastic syndrome- Euronetwork consortium for paraneoplastic neurological disorders, and current adaption for neuropathies. All patients underwent serum tests for pathogens and autoantibodies including antinuclear antibodies, anticardiolipin antibodies, antineutrophil cytoplasmic antibodies, AQP4-Ab and MOG-Ab, as well as CSF tests for malignant cells under microscope. Serum paraneoplastic antibodies were detected in PON patients. Monkey cerebellar tissue-based assay was used to detect unknown serum anti-neuron antibodies in PON patients with negative paraneoplastic antibody testing results.
Fourteen ON patients were classified as four groups based on their clinical and MRI characteristics, as well as serum and CSF testing results: [1] definite PON, 6 cases (11 eyes); [2] possible PON, 3 case (5 eyes); [3] meningeal carcinomatosis-associated optic neuropathy (MCON), 4 cases (6 eyes); [4] infiltrative optic neuropathy (ION), 2 cases (2 eyes). Malignant cells were found under microscope in CSF samples from MCON and ION patients, contrast to no malignant cells in CSF samples from PON cases. All 14 ON patients with malignant tumors showed negative results in serum tests for pathogens and autoantibodies. Serum paraneoplastic antibodies were tested in PON patients, anti- CV2, anti-Yo, and anti- amphiphysin were detected positive in 2, 1, and 1 case, respectively, in definite PON group, whereas no serum paraneoplastic antibody detected in possible PON group. Two unknown serum antineuronal antibodies (an anti- Purkinje cell antibody and an anti-granular cell antibody) were detected using monkey cerebellar tissue-based assay in 2 of 5 PON patients with negative paraneoplastic antibody test results.
Serum and CSF tests are of great importance in differentiating different subtypes of ON with malignant tumors. Current diagnosis of PON still depends on combination of clinical and MRI manifestations, as well as serum and CSF tests. Tissue-based assay may help to detect new biomarkers for ON etiology and diagnosis.
评估血清和脑脊液（CSF）检测在伴发恶性肿瘤的视神经病变（ON）患者中的价值。
本研究纳入了 14 例经临床诊断为伴发恶性肿瘤但 MRI 未见颅内或眶内肿块的 ON 患者。收集并分析了详细的病历资料，包括病史、全面眼科检查、眼底彩照、视野检查、眼眶 MRI 检查、血清和 CSF 检测数据。根据副肿瘤综合征-Euronetwork 联合会的副肿瘤神经疾病推荐标准（2004 年）和目前对神经病变的适应标准，诊断为副瘤性视神经病变（PON）。所有患者均进行了病原体和自身抗体的血清学检查，包括抗核抗体、抗心磷脂抗体、抗中性粒细胞胞质抗体、AQP4-Ab 和 MOG-Ab，以及显微镜下 CSF 检测恶性细胞。PON 患者进行血清副瘤抗体检测。PON 患者中，采用猴小脑组织检测法检测副瘤抗体检测阴性患者的未知血清抗神经元抗体。
根据患者的临床和 MRI 特征以及血清和 CSF 检测结果，将 14 例 ON 患者分为 4 组：[1]明确 PON，6 例（11 眼）；[2]可能 PON，3 例（5 眼）；[3]脑膜癌病相关性视神经病变（MCON），4 例（6 眼）；[4]浸润性视神经病变（ION），2 例（2 眼）。与 PON 患者的 CSF 样本中未发现恶性细胞相比，MCON 和 ION 患者的 CSF 样本中可在显微镜下发现恶性细胞。所有 14 例伴发恶性肿瘤的 ON 患者的病原体和自身抗体血清学检查均为阴性。PON 患者进行血清副瘤抗体检测，明确 PON 组中 2 例检测到抗 CV2、抗 Yo，1 例检测到抗 amphiphysin 阳性，可能 PON 组中未检测到血清副瘤抗体。2 例 PON 患者的副瘤抗体检测结果阴性，采用猴小脑组织检测法检测到 2 种未知的血清抗神经元抗体（抗蒲肯野细胞抗体和抗颗粒细胞抗体）。
血清和 CSF 检测在鉴别伴发恶性肿瘤的不同类型 ON 中具有重要意义。目前 PON 的诊断仍依赖于临床和 MRI 表现以及血清和 CSF 检测的综合结果。组织检测可能有助于发现新的 ON 病因和诊断生物标志物。
