Abstract:

Background  Anti-CV2/CRMP5 antibodies-associated paraneoplastic peripheral neuropathy (PPN) is a poorly understood disease due to its rarity. This study aimed to summarize the clinical manifestations, electrophysiological and pathological characteristics of anti-CV2/CRMP5 antibodies-associated PPN and reviewed related literatures, so as to improve the understandings on this disease. Methods  The clinical data of 2 patients with anti-CV2/CRMP5 antibodies-associated PPN were retrospectively reviewed, including their clinical manifestations, electrophysiological and pathological characteristics, treatment and follow-up.  Results  Case 1 was a 52-year-old woman who initially presented with a 3-year history of slowly progressive numbness of limbs, which presented from right leg and gradually spread to her left arm and right ring finger and little finger. Then she suffered from weakness of left leg, weakened muscle strength of left hand and had difficultly in lifting left arm. Serum anti-CV2/CRMP5 antibodies were weakly positive, and anti-Hu, Yo, Ri, amphiphysin antibodies were negative. EMG showed peripheral neurogenic damage. Nerve tissue biopsy showed chronic severe active axonal peripheral neuropathy. There was no improvement after two courses of intravenous immunoglobulin (IVIg) and then she received steroid pulse treatment and sequential therapy. The symptom was still not improved 2 months after discharge, and oral azathioprine was added. Follow-up in one year, the numbness and weakness were improved. Case 2 was an 18-year-old man who presented with one-month history of limbs weakness with fluctuating symptoms and positive results of fatigue test. Serum anti-CV2/CRMP5 antibodies were positive. Acetylcholine receptor antibodies (AchR-Ab) was 27.47 nmol/L, and cerebrospinal fluid (CSF) protein was 1360 mg/L. EMG showed symmetrical involvement of sensorimotor nerves of all limbs, mainly demyelination. Repetitive nerve stimulation (RNS) showed low-frequency amplitude decreased progressively. Needle biopsy of thymus showed type B3 thymoma. The patient was diagnosed as myasthenia gravis (MS), peripheral neuropathy and type B3 thymoma. He was treated by IVIg, oral pyridostigmine bromide and chemotherapy. EMG 10 months after discharge showed worsened neurogenic damage of four limbs. Serum anti-CV2/CRMP5 antibodies were still positive.  Conclusions  Anti-CV2/CRMP5 antibodies-associated paraneoplastic peripheral neuropathy patients can present a symmetric or asymmetric sensorimotor peripheral neuropathy with either axonal or demyelinating damage. Immunotherapy maybe effective.

Key words: Paraneoplastic polyneuropathy, Electromyography, Pathology

摘要：

研究背景 抗CV2/CRMP5 抗体相关副肿瘤性周围神经病临床少见。本文报道2 例抗CV2/CRMP5 抗体相关副肿瘤性周围神经病患者，总结其临床表现、电生理学和病理学特点，并复习相关文献，以期提高临床对疾病的认识。方法 回顾2 例抗CV2/CRMP5 抗体相关副肿瘤性周围神经病患者的诊断与治疗经过，分析其临床表现、电生理学和病理学特点、治疗及随诊。结果 例1 为52 岁女性患者，以进行性四肢麻木、无力3 年入院，自右下肢起病，逐渐进展至左上肢和右手无名指、小指，此后出现左下肢无力、左手肌力减弱、左上肢抬举困难。血清抗CV2/CRMP5 抗体呈弱阳性，抗Hu、Yo、Ri 抗体和抗两性蛋白抗体阴性。肌电图提示周围神经源性损害。神经组织活检证实慢性重度活动性轴索性周围神经病。予2 次静脉注射免疫球蛋白，症状无明显改善，遂予激素冲击治疗后序贯治疗。出院后2 个月随诊，症状无缓解，增加硫唑嘌呤口服；1 年后随诊，麻木、无力有所减轻。例2 为18 岁男性患者，以四肢无力1 月余入院，尤以近端显著，有晨轻暮重现象。血清抗CV2/CRMP5 抗体阳性，抗乙酰胆碱受体抗体27.47 nmol/L，脑脊液蛋白定量1360 mg/L。肌电图提示四肢感觉运动神经均受累，双侧对称，以脱髓鞘损害为主；重复神经电刺激可见低频刺激波幅递减现象。胸腺组织活检证实胸腺瘤B3 型。临床诊断为重症肌无力，周围神经病，胸腺瘤B3 型。予静脉注射免疫球蛋白和溴吡斯的明口服以及药物化疗。出院后10 个月复查肌电图四肢周围神经源性损害较前加重，血清抗CV2/CRMP5 抗体仍阳性。结论 抗CV2/CRMP5 抗体相关副肿瘤性周围神经病可以表现为对称性或不对称性感觉运动性周围神经病，轴索和髓鞘均可受累，免疫治疗可能有效。

关键词: 副肿瘤性多发性神经病, 肌电描记术, 病理学