神経筋接合部病態の定性・定量的評価―超微形態と組織化学

Histochemical Findings of and Fine Structural Changes in Motor Endplates in Diseases with Neuromuscular Transmission Abnormalities

はじめに

　神経筋接合部の疾患としては，コリン作動性アセチルコリン受容体（acetylcholine receptor：AChR）に対する自己抗体による重症筋無力症（myasthenia gravis：MG）や神経終末（nerve terminal：NT）部に存在するP/Q型電位依存性カルシウムチャネル（voltage-dependent calcium channelopathy：VGCC）に対する自己抗体によるLambert-Eaton筋無力症候群（Lambert-Eaton myasthenic syndrome：LEMS）がよく知られている。そして，全身型MGの中で抗AChR抗体が血清中に検出されないseronegative MG患者の存在が知られていた^1，2）。2001年には，これらseronegative MG患者の70％で筋特異的チロシンキナーゼ（muscle-specific tyrosine kinase：MuSK）に対する自己抗体で発症するMGの報告がなされた^3）。近年，神経筋接合部の形成に必須であるMuSK，Dok-7，rapsinそしてlow-density lipoprotein receptor-related protein 4（LRP 4）の異常によっても神経筋伝達の障害が生じることが報告されている^4－6）。これら神経筋接合部疾患の運動終板の微細構造は，同一患者であっても筋線維により正常から異常の所見を呈していることが報告されている^7）。したがって，運動終板は，できるだけ数多く観察することが必要となる。本稿では，神経筋接合部の組織化学染色，定量的解析に関して紹介する。

Abstract

　We herein review the histochemical findings and fine structural changes of motor endplates associated with diseases causing neuromuscular transmission abnormalities.　In anti-acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG),type 2 fiber atrophy is observed,and the motor endplates show a reduction in the nerve terminal area,simplification of the postsynaptic membrane,decreased number of acetylcholine receptors,and deposition of immune complexes.　In anti-MuSK antibody-positive MG,the fine structure shows a decrease in the postsynaptic membrane length,but the secondary synaptic cleft is preserved.　There is no decrease in the number of AChRs,and there are no deposits of immune complexes at the motor endplates.　Patients with Lambert-Eaton myasthenic syndrome show type 2 fiber atrophy,their motor endplates show a decrease in both the mean postsynaptic area and postsynaptic membrane length in the brachial biceps muscle.　Congenital myasthenic syndrome with episodic apnea is characterized only by small-sized synaptic vesicles; the postsynaptic area is preserved.　In subjects with congenital myasthenic syndrome with acetylcholinesterase deficiency,quantitative electron microscopy reveals a significant decrease in the nerve terminal size and presynaptic membrane length; further,the Schwann cell processes extend into the primary synaptic cleft,and partially or completely occlude the presynaptic membrane.　The postsynaptic folds are degenerated,and associated with pinocytotic vesicles and labyrinthine membranous networks.　Patients with slow-channel congenital myasthenia syndrome show type 1 fiber predominance,and their junctional folds are typically degenerated with widened synaptic space and loss of AChRs.　Patients with AChR deficiency syndrome caused by recessive mutations in AChR subunits also show type 1 fiber predominance,and while most junctional folds are normal,some are simplified and have smaller than normal endplates.　Rapsin and MuSK mutations cause type 1 fiber predominance,and the small postsynaptic area is associated with AChR decrease.