オプソクローヌス・ミオクローヌス症候群

Paraneoprastic Opsoclonus-myoclonus Syndrome : A Review

はじめに

　傍腫瘍性オプソクローヌス・ミオクローヌス症候群（paraneoprastic opsoclonus-myoclonus syndrome：POMS）は，悪性腫瘍の遠隔効果によりさまざまな神経症状を呈する傍腫瘍性神経筋疾患の病型の1つであり，特異な眼球運動であるオプソクローヌスに小脳失調やミオクローヌスを伴う比較的稀な疾患である。本症に最も特徴的なオプソクローヌスとは，リズム，方向，振幅がいずれも不規則な衝動性眼球運動（サッカード）が，絶え間なく出現する神経徴候をいう^1－5）。近年，さまざまな自己抗体がPOMSにおいて同定され，自己免疫性神経筋疾患の1つであると考えられるようになり，この分野から病態解明へのアプローチが日進月歩で進んでいる。本稿では，特にPOMSに特徴的なオプソクローヌスの免疫学的病因と病態生理学に焦点をあてつつ，POMSの臨床的特徴，病因と鑑別疾患，検査，治療，経過と予後についても記載する。

Abstract

　The aim of this article is to review the paraneoplastic opsoclonus-myoclonus syndrome (POMS).　Opsoclonus is characterized by involuntary,arrhythmic,chaotic,multi-directional saccades with horizontal,vertical and torsional components,and it is commonly accompanied by cerebellar ataxia and myoclonic jerks in the trunk and limbs.　Parainfectious brainstem encephalitis,toxic-metabolic disturbances and others condition should be considered as potential causes of these symptoms.　In adults,POMS is most commonly associated with small-cell lung cancer,breast cancer,and ovarian cancer.　In children,a neuroblastoma is detected in approximately 50% of cases.　Many autoantibodies have been detected in patients with POMS: this finding suggests the involvement of a humoral immune mechanism.　However,most patients are seronegative for these autoantibodies.　This implies that a cell-mediated immune mechanism may also be involved in the pathogenesis of opsoclonus.　Although the exact pathophysiology mechanism of opsoclonus remains unclear,recent reports suggest that disinhibition of the fastigial nucleus of the cerebellum is involved.　In children,the immunotherapy with corticosteroids,intravenous immunoglobulin,adrenocorticotropic hormone,plasma exchange,cyclophosphamide,or rituximab is used.　Although opsoclonus is often responsive to therapy,the high incidence of sequelae related to motor function,speech,behavior,and sleep is an important problem.　In adults,POMS is less responsive to immunotherapy and improves only with tumor resection.　In order to develop novel and effective therapeutic strategies,further studies on the immunopathogenesis and pathophysiology of POMS are required.