傍腫瘍性小脳変性症および筋無力症候群を呈した肺小細胞癌の1例

A Case of Small Cell Carcinoma of the Lung Associated with Paraneoplastic Cerebellar Degeneration and Lambert-Eaton Myasthenic Syndrome

亜急性に四肢協調運動障害，構音障害，失調性歩行，両側眼瞼下垂，複視，眼振などが出現進行した51歳男性例を報告した。胸部X線，CTにて左肺門部腫瘤が認められ，生検にて肺小細胞癌と診断された。筋力検査で5である右短拇指内転筋（APB）の複合筋誘発電位（CMAP）が2.0mVと低値で，同神経の低頻度反復刺激試験（3Hz）で42％のwaningとpost-exercise testでの73％のCMAP増大を認めた。肺小細胞癌に傍腫瘍性小脳変性症と筋無力症候群が合併したものと診断した。各種抗神経抗体を検索したところ，抗P/Q型電位依存性カルシウムチャネル（VGCC）抗体のみ高値陽性（1,920pM）であった。化学療法施行にて腫瘍マーカーの低下とともに，小脳症状の軽度改善と抗P/Q型VGCC抗体の抗体価の低下を認めた。抗VGCC抗体が，LEMSの病態だけでなく，一部のPCDの発生機序にも何らかの関与がある可能性がある。

A 51-year-old male who showed severe ataxia, dysarthria, bilateral blepharoptosis, diplopia and nystagmus with the subacute onset was reported. The chest roentgenogram and CT scan revealed mass lesions at the hilus of the left lung. The tumor markers, NSE and ProGRP, were elevated; 12.8 ng/ml （≦10） and 140.7 pg/ml （≦46）, respectively. The biopsy was performed surgically and the small cell carcinoma of the lung was confirmed pathologically. His cerebellar symptoms were considered to be caused by the paraneoplastc cerebellar degeneration. However, the blepharoptosis was peculiar. The electrophysiological studies were carried out. The muscle strength test of the right APB muscle was 5. But the supramaximum stimulation of the right median nerve evoked only 2.0 mV of CMAP of the right APB muscle. The repetitive stimulation tests of the same nerve showed that 3 Hz stimulation resulted in 42％ waning but 20 Hz stimulation evoked no waxing. The post-exercise test of the right APB muscle showed 73％ increase of the CMAP.

　These findings indicated that he also suffered from Lambert-Eaton myasthenic syndrome. The titer of the antibody against the P/Q type voltage-gated calcium channel （VGCC） was remarkably elevated, 1,920pM. None of the following antibodies were detected ; they included antibodies against acetylcholine receptor, Hu, Yo, Ri, Ma-2, CRMP-5, amphiphysin and glutamic acid dehydrogenase.

　The small cell carcinoma was treated with the combination of irinotecan hydrochloride and cisplatin, leading to the reduction of the mass lesions and the tumor markers. His cerebellar symptoms improved slightly but his blepharoptosis was unchanged. The titer of antibody against the P/Q type VGCC reduced remarkably to 451.8 pM.

　We reviewed reported cases associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome and discussed the relation between the paraneoplastic syndromes and autoantibodies.

（Received : July 14, 2005）