抗Yo抗体阳性的副肿瘤性小脑变性分析

Anti-Yo antibody-associated paraneoplastic cerebellar degeneration： a report of 6 patients

目的通过抗Yo抗体检测辅助诊断副肿瘤性小脑变性，并对患者进行临床观察。方法对2012-2013年临床怀疑副肿瘤神经综合征患者的血清和脑脊液标本采用蛋白免疫印迹法进行抗Yo抗体检测，对其中抗Yo抗体阳性的亚急性小脑变性患者进行临床观察和随访。结果共发现6例抗Yo抗体阳性的亚急性小脑变性患者，均为女性，平均年龄55岁。均表现为显著的小脑性共济失调，从起病到症状高峰的时间为1—9周，平均6．23周。均以行走不稳、头晕起病，发展为累计四肢和躯体的共济失调，均有自发性眼震，其中旋转性眼震3例，水平性眼震2例，眼阵挛样眼震1例。其他表现包括饮水呛咳、吞咽困难、复视、精神行为异常等。改良Rankin评分4—5分，为中重度功能障碍。脑脊液白细胞计数升高者4例，脑脊液蛋白升高者2例。脑脊液细胞学3例提示淋巴细胞性炎症。4例脑脊液抗Yo抗体阳性，2例脑脊液抗Yo抗体阴性。全部患者血清抗Yo抗体检测均阳性，头MRI检查5例未见明显异常，1例双侧小脑，颞叶内侧高信号。5例合并有恶性肿瘤，其中4例卵巢癌，1例膀胱癌。5例进行抗肿瘤治疗。3例患者接受了静脉丙种球蛋白的免疫治疗，其中1例神经科症状部分缓解。结论抗Yo抗体作为一种经典的副肿瘤性抗神经元抗体，与副肿瘤性小脑变性存在对应关系；对于抗Yo抗体阳性的小脑性共济失调患者，需要重点排查卵巢癌等潜在恶性肿瘤。抗肿瘤治疗和免疫治疗对副肿瘤性小脑变性的神经功能效果不明显。

Objective Paraneoplastic cerebellar degeneration （PCD） is a neurological syndrome characterized by subacute cerebellar ataxia, specific tumour types and associated antineuronal antibodies. We attempted to identify patient-, tumour- and treatment-related characteristics associated with PCD with anti-Yo antibodies. Methods We examined the antineuronal antibodies associated and studied the neurological symptoms and signs, associated tumours, disability of PCD with anti-Yo antibodies. Results Six patients had anti-Yo antibody-associated PCD. All patients are female with mean age of 55 years. All cases presented with subacute cerebellar ataxia progressive over 1 to 9 weeks （mean 6. 23 weeks）. The majority of patients had both truneal and appendicular ataxia with unstable gait and dizziness. Spontaneous nystagmus presented in all cases including rotary nystagmus in three cases, horizontal nystagmus in two cases, opsoclonus-like nystagmus in one case. Dysarthria, dysphasia, double vision and behavior changes presented in some cases. Modified Rankin Scale scores were 4 -5, indicating severe disability. On cerebrospinal fluid examination, mild increases of white blood cell counts were found in four cases and mild elevation of protein concentration in two cases. Cerebrospinal fluid cytology showed lymphocytic inflammation in 3 cases. The most commonly associated tumours were ovary cancer in four cases while cancer of bladder was found in one patient. Only one patient improved neurologically after receiving anti-tumour treatment and immunotherapy with intravenous immunoglobulin in 3 cases. Conclusions Anti-Yo antibodies are well- characterised on coneuronal antibodies associated with PCD related to gynaecological cancer. Diagnosis and treatment of underlying neoplasm is critical for the patient with subacute cerebellar ataxia and positive anti- Yo antibody. Anti-Yo antibody-associated PCD usually results in severe disability with poor prognosis even after anti-tumor and immunotherapy.