急性片眼性眼瞼下垂と眼球運動制限を伴った抗SOX1抗体陽性の傍腫瘍性神経症候群の1例

A case of anti-SOX1 antibody-positive paraneoplastic neurological syndrome with acute unilateral ptosis and eye dysmotility

要約　目的：急性片眼性眼瞼下垂と眼球運動制限を伴った抗SRY-Related HMG-Box Gene 1（SOX1）抗体陽性の傍腫瘍性神経症候群（PNS）の1例を経験したので報告する。

症例：82歳，男性。突然の眼瞼下垂，複視により，同日当科受診した。右眼瞼下垂，右眼内転，上転障害がみられたが，瞳孔不同はなく，対光反射も保たれていた。右眼は浅前房，左眼は眼内レンズ挿入眼であるほか，眼内に特記所見はなかった。右動眼神経不全麻痺を疑い，頭部単純MRI検査を施行したが異常はみられなかった。症状に日内変動はなく，神経診察にて四肢の神経学的異常あり，精査目的で入院となった。体幹部造影CTで右肺下葉の腫瘤および右肺門・縦隔リンパ節の腫脹を指摘，気管支鏡下生検で縦隔肺門部型小細胞肺癌の診断となった。この間に右眼瞼下垂と眼球運動障害の増悪がみられた。初診から39日後に化学療法（カルボプラチン，エトポシド）を開始，7日目より右眼瞼下垂が改善した。経過からPNSが疑われ，血液検査で抗SOX1抗体陽性が判明した。化学療法6コース終了時点で自覚症状は消失，ヘス赤緑試験もほぼ正常範囲内に戻り，瞼裂高の左右差もみられなかった。

結論：抗SOX1抗体は小細胞肺癌，および自己免疫性小脳変性やランバート・イートン筋無力症候群との関連が強く，抗SOX1抗体陽性のPNSでは片眼性動眼神経麻痺の報告はない。片眼性動眼神経麻痺を疑った際には，傍腫瘍性神経症候群も鑑別に挙げる必要がある。

Abstract　Purpose：To report a case of anti- SRY-Related HMG-Box Gene 1（SOX1）antibody-positive paraneoplastic neurological syndrome（PNS）with acute unilateral ptosis and eye dysmotility.

Case：An 82-year-old man with a history of atrial fibrillation, dementia, and smoking was first admitted to our hospital following sudden ptosis and diplopia. The right eye had ptosis, and an ocular motility examination with the Hess chart found limited adduction and elevation. The light reflex of both eyes was normal. Of the right eye, anterior chamber was shallow, and the lens had mild cataract. The left eye had an intra ocular lens. Pupil-sparing oculomotor nerve palsy was suspected. Brain magnetic resonance imaging and magnetic resonance angiography did not show any remarkable abnormality. The symptoms remained unchanged during the day. Neurological examination revealed some abnormalities in the limbs, and the patient was hospitalized under the neurology department for further investigation. Contrast-enhanced computed tomography findings led to the suspicion of a tumor in the lower lobe and hilum of the right lung and mediastinum. A diagnosis of small cell lung cancer（SCLC）was made on the basis of fiberoptic bronchoscopic biopsy findings. Meanwhile, the unilateral ptosis and ocular dysmotility deteriorated. Chemotherapy consisting of carboplatin and etoposide was initiated, and the ptosis improved seven days after the start of therapy. The clinical course of the disease indicated a PNS, and a laboratory test showed positive anti-SOX1 antibody. After six courses of chemotherapy, the subjective symptoms resolved, and ocular motility and the ptosis has normalized.

Conclusion：Anti-SOX1 antibody is associated with paraneoplastic cerebellar degeneration, Lambert-Eaton myasthenic syndrome, and SCLC. To the best of our knowledge, this is the first report of a case of anti-SOX1 antibody-positive PNS with pupil-sparing oculomotor nerve palsy. PNS should be considered in the differential diagnosis if oculomotor nerve palsy is observed.