重症肌无力伴胸腺瘤相关CRMP5/CV2抗体阳性副肿瘤性神经综合征：一例病例报告及文献复习

文献信息

中文摘要

目的： 阐明重症肌无力（MG）伴胸腺瘤相关CRMP5/CV2抗体阳性副肿瘤性神经综合征（PNS）的临床特征、诊断标准、治疗策略及预后，从而提高临床对这种罕见重叠自身免疫性疾病的认识。
方法： 我们回顾性分析了一名53岁男性患者的临床资料，该患者以外周神经损伤为首发表现，随后被诊断为MG、侵袭性胸腺瘤和CRMP5/CV2抗体阳性PNS。同时进行了相关国际文献的全面复习。
结果： 患者病程2年，最初表现为肢体麻木和步态不稳，并逐渐出现构音障碍、吞咽困难、复视以及具有特征性昼夜波动的肌无力症状（傍晚加重，晨起减轻）。根据美国重症肌无力基金会（MGFA）临床分型，患者基线时为IIIb型（中度全身型MG，以口咽部受累为主）。血清学检查证实血清乙酰胆碱受体（AChR）抗体阳性，血清和脑脊液（CSF）中CRMP5/CV2抗体均阳性。电生理检查显示多发性外周神经损害，低频重复神经刺激（RNS）出现显著递减反应。胸部CT显示前纵隔侵袭性胸腺瘤。患者接受了胸腔镜胸腺切除术，随后序贯给予糖皮质激素、静脉注射免疫球蛋白和环磷酰胺治疗，以及对症支持治疗和抗感染管理。治疗后，神经系统症状显著改善，随访期间病情保持稳定。
结论： MG伴胸腺瘤相关CRMP5/CV2抗体阳性PNS是一种罕见的临床实体，起病不典型，极易误诊。联合检测副肿瘤抗体和胸部影像学对早期诊断至关重要，胸腺切除术联合规范化免疫治疗可有效改善患者的临床症状和长期预后。

英文摘要

OBJECTIVE: To delineate the clinical characteristics, diagnostic criteria, therapeutic strategies, and prognosis of myasthenia gravis (MG) with thymoma-associated CRMP5/CV2 antibody-positive paraneoplastic neurological syndrome (PNS), thereby enhancing clinical recognition of this rare overlapping autoimmune disorder.
METHODS: We retrospectively analyzed the clinical data of a 53-year-old male patient presenting with peripheral nerve injury as the initial manifestation, who was subsequently diagnosed with MG, invasive thymoma, and CRMP5/CV2 antibody-positive PNS. A comprehensive review of the relevant international literature was also conducted.
RESULTS: The patient had a 2-year disease course, initially presenting with limb numbness and unsteady gait, and gradually developing dysarthria, dysphagia, diplopia, and myasthenic weakness with characteristic diurnal fluctuation (worsening in the evening and improving in the morning). According to the Myasthenia Gravis Foundation of America (MGFA) clinical classification, the patient was categorized as Class IIIb (moderate generalized MG with predominant oropharyngeal involvement) at baseline. Serological tests confirmed positive for acetylcholine receptor (AChR) antibody in serum, as well as CRMP5/CV2 antibody in both serum and cerebrospinal fluid (CSF). Electrophysiological examinations revealed multiple peripheral nerve damage and a significant decremental response to low-frequency repetitive nerve stimulation (RNS). Chest CT demonstrated an invasive thymoma in the anterior mediastinum. The patient underwent thoracoscopic thymectomy, followed by sequential treatment with glucocorticoids, intravenous immunoglobulin and cyclophosphamide, as well as symptomatic supportive care and anti-infective management. After treatment, the neurological symptoms were significantly improved, and the condition remained stable during follow-up.
CONCLUSION: MG with thymoma-associated CRMP5/CV2 antibody-positive PNS represents a rare clinical entity with atypical onset and is highly susceptible to misdiagnosis. Combined detection of paraneoplastic antibodies and chest imaging is critical for early diagnosis, and thymectomy combined with standardized immunotherapy can effectively improve the clinical symptoms and long-term prognosis of patients.