傍腫瘍性小脳変性症とLambert-Eaton筋無力症症候群を呈した抗P/Q型VGCC抗体陽性の原発性肺重複癌の1例

Paraneoplastic Cerebellar Degeneration and Lambert-Eaton Myasthenic Syndrome Associated with Anti P/Q-type Voltage-gated Calcium Channel Antibody in a Patient with Primary Double Lung Cancer

はじめに

　傍腫瘍性神経症候群は，腫瘍における神経系への直接浸潤や転移ではなく，遠隔効果による自己免疫機序によって発症する。Lambert-Eaton筋無力症症候群（Lambert-Eaton myasthenic syndrome：LEMS）は肺小細胞癌を高率に合併し，P/Q型電位依存性カルシウムチャネル（P/Q-type voltage-gated calcium channel：P/Q型VGCC）に対する自己抗体が，神経終末のP/Q型VGCC量を減少させ，LEMSを発現させると推測されている。LEMSに小脳性運動失調を合併する例が散見されるようになり，抗P/Q型VGCC抗体が傍腫瘍性小脳変性症（paraneoplastic cerebellar disorder：PCD）にも関与することが示唆されている^1－7）。われわれは，急性の小脳性運動失調を発症した症例で当初PCDを疑い，細気管支肺胞上皮癌を同定した。その後，抗P/Q型VGCC抗体を伴うLEMSの存在が明らかとなり，肺小細胞癌を証明し，結果として原発性肺重複癌であることを確認した。抗P/Q型VGCC抗体陽性のLEMSでは，従来指摘されている肺小細胞癌を明らかにすることが治療を選択するうえで極めて重要であり，積極的に検索する必要性を強調したいと考えたので報告する。

Abstract

　We report the case of a 50-year-old man with paraneoplastic cerebellar degeneration (PCD) and Lambert-Eaton myasthenic syndrome (LEMS) associated with primary double lung cancer.　He developed acute progressive double vision, slurred speech, and gait disturbance.　Neurological examination revealed diplopia, mild ptosis, bilateral horizontal gaze-evoked nystagmus, and cerebellar limb and truncal ataxia.　The diffusion image of brain magnetic resonance imaging (MRI) revealed no abnormal findings in the cerebellum.　On the basis of the diagnosis of acute cerebelitis, he was given methylprednisolone pulse therapy followed by oral prednisolone, which gradually improved his neurological signs and symptoms.　The analysis of the possible etiology suggested that the PCD was induced by lung cancer, which led to ataxia.　A chest computed tomography scan revealed mass lesions of irregular shape and unclear margins in the upper lobe of the right lung and a small nodule tumor in the upper lobe of the left lung.　We performed transbronchial needle aspiration and detected the bronchioloalveolar carcinoma of the right lung.　An electromyogram showed waxing phenomenon in the ulnar nerve at high-frequency (50Hz) stimulation.　The serum levels of anti-P/Q-type voltage-gated calcium channel (VGCC) antibody were elavated in the patient.　These findings confirmed that the pathogenesis of the condition of this patient to be associated with LEMS.　His cerebellar symptoms were considered to be caused by the PCD, and the diplopia, ptosis, and hyporeflexia were attributed to LEMS.　We performed upper left lobectomy with mediastinal lymphnode dissection via video-assisted thoracoscopic surgery.　A histological study detected small cell carcinoma.　A diagnosis of double primary lung cancer was made.　Physicians need to be aware that patients may develop PCD and LEMS associated with anti-VGCC antibody caused by small cell lung cancer, and a mass survey should be conducted and careful examinations performed.

(Received: February 23,2009,Accepted: May25,2009)