有镶边空泡的远端肌病九例临床和病理研究

目的 探讨有镶边空泡的远端肌病(DMRV)的临床和病理特点。方法 分析我院1990～2001年9例DMRV患者的临床表现和肌活检组织病理特点，其中6例进行透射电镜观察。结果 平均起病年龄25岁，全部患者均为下肢无力起病，远端受累明显，下肢近端、骨盆带肌和上肢肌群也逐渐受累。肌电图示4例为肌源性损害，5例为混合性损害。其病理改变主要为镶边空泡纤维、肌纤维萎缩和肌间质增生，肌纤维坏死相对较轻。电镜观察6例，5例可见大量的髓样结构聚集，4例发现肌质内细丝包涵体，2例有核内包涵体，其中1例可见增大的肌核内染色质完全被细丝取代，核膜破裂，核内细丝包涵体释出进入肌质内。结论 发生在我国的DMRV与日本报道的病例在临床和病理特点上基本一致。电镜观察结果提示胞质内的细丝包涵体来源于崩解的肌核，肌核改变先于肌原纤维的破坏，镶边空泡的形成很可能是肌核崩解的结果。     

包涵体肌炎（综述）

１　历史回顾包涵体肌炎（ｉｎｃｌｕｓｉｏｎｂｏｄｙｍｙｏｓｉｔｉｓ,ＩＢＭ）是一种慢性炎症性肌病。其主要病理特点是肌浆或肌核内有管状细丝包涵体。Ｙｕｎｉｓ［１］首先提出ＩＢＭ这一疾病名称。在此之前Ａｄａｍｓ［２］等报告了１例肌细胞内包涵体肌病,这种包涵体在光镜下与Ｙｕｎｉｓ描述的包涵体很相似。后来Ｃｈｏｕ［３］在１例慢性多发性肌炎患者的肌肉中发现了这种包涵体,当时称之为粘病毒样结构。直至１９７８年Ｃａｒｐｅｎｔｅｒ［４］对１４例ＩＢＭ的临床病理特点进行了总结,并正式确立了ＩＢＭ为一独立疾病。此后…     

包涵体肌炎的临床与病理特点(附2例报告)

目的 探讨包涵体肌炎的临床与病理特点。方法 对2例包涵体肌炎患者的临床表现、肌肉组织化学、酶组织化学和超微结构等资料进行分析。结果 本组2例患者分别于41岁及54岁发病,均以双下肢无力起病,远端重于近端,并逐渐向上肢发展;血清肌酶轻～中度升高;肌电图示肌源性损害;肌肉活检光镜下主要表现为肌纤维内出现镶边空泡,少数变性坏死纤维,伴炎性细胞浸润。电镜观察证实肌浆内有大量涡轮状髓样小体及管状细丝包涵体。结论 包涵体肌炎临床表现缺乏特异性,肌肉病理学检查是诊断包涵体肌炎的重要手段。     

Nonaka肌病伴面部肌肉受累

目的 报道1个伴随面部肌肉受累及的Nonaka型远端性肌肉病家系的临床和病理特点，讨论其发病机制。方法 先证者在中年早期起病。主要临床表现为胫前肌为主的四肢远端肌无力和肌萎缩，伴随有面肌和胸锁乳突肌力弱以及眼睑下垂，股四头肌不受累。肌酶轻度升高。肌电图提示肌源性损害。对患者进行胫前肌活检，进行组织学，酶组织化学和超微结构检查。家族中其妹妹也具有相同的临床表现。出现下肢远端为主的肌无力和肌萎缩。结果 肌肉病理改变特点是出现肌纤维肥大和萎缩。伴随核内移和肌纤维分裂现象。在部分肌纤维内可见镶边空泡和胞浆体。电镜下可见肌纤维内和核内的管丝包涵体以及髓样小体，其中出现在膜下的管丝包涵体具有细胞核的轮廓，可以看到细胞核变性后形成致密破碎结构。结论 结合患者的家庭史，临床表现和病理学改变特点。此患者可以考虑为Nonaka肌病，我们证实此病可以伴随面部肌肉的受累及。其发病机制可能与肌核的变性有关。     

散发性包涵体肌炎临床、电生理及病理特点

目的探讨散发性包涵体肌炎的临床、电生理及病理特点。方法回顾性分析5例散发性包涵体肌炎患者的临床资料。结果 5例患者均为男性,发病年龄30~54岁,平均43.2岁,出现症状至确诊平均8年。5例患者受累肌肉分布无规律,肌酸激酶正常或轻度增高,EMG呈肌源性损害、部分伴神经源损害或周围神经损害或肌强直电位,肌肉活检5例均有镶边空泡伴肌纤维炎性浸润,1例见不整边红纤维,电镜下3例有管丝包涵体。结论因无特征性临床表现,散发性包涵体肌炎早期诊断较为困难,其诊断主要依赖于肌肉活检。     

散发性包涵体肌炎临床病理分析

目的探讨散发性包涵体肌炎(sIBM)患者的临床及病理特点。方法收集2例于2008年至2010年就诊并明确诊断为s1BM的患者临床、病理资料。两例患者均有股四头肌无力和萎缩,1例出现肢体远端无力和上肢无力。2例患者均进行了肌肉活体组织检查标本的组织学、酶组织化学染色和免疫组织化学染色。结果 2例患者肌酶均轻度升高。肌电图检查示1例呈肌源性损害,1例呈神经源性损害。2例患者的骨骼肌主要病理改变都是肌内衣炎细胞浸润、肌纤维萎缩,肌纤维内嗜碱性镶边空泡。免疫组织化学染色提示CD8+淋巴细胞浸润为主,1例患者镶边空泡肌纤维内Ubiquitin染色阳性。结论本文2例sIBM以股四头肌损害明显,病情缓慢进展,依靠肌肉活检确定诊断。     

包涵体肌炎11例临床及组织病理报告

目的 探讨包涵体肌炎的诊断标准。方法 分析了11例包涵体肌炎病人的临床表现、组织化学。碱性刚果红染色9例，电镜检查2例。结果 全部病人均在42岁后发病，表现为远、近端肌肉力弱，2例肌电图检查显示肌源性改变，11例均有边缘着色性空泡及炎性改变，9例有淀粉样蛋白沉积物，有胞核或胞质细丝包涵体各1例。结论 包涵体肌炎的所有诊断指标中，无一项有决定性或行征性，需要进行综合判断。     

伴有破碎红纤维的包涵体肌炎的临床及病理学特点(附1例报告)

目的 探讨伴有破碎红纤维的包涵体肌炎的临床及病理学特点.方法 回顾性分析1例伴有破碎红纤维的包涵体肌炎患者的临床资料.结果 本例为中年男性,四肢近端进行性肌萎缩,血清肌酶轻度增高,肌电图示肌源性损害.肌活检示部分萎缩的肌纤维出现镶边空泡,空泡内含有嗜碱性颗粒,部分坏死肌纤维有吞噬细胞及炎症细胞浸润,改良Gomori染色见破碎红纤维,细胞色素酶染色见蓝纤维;泛素染色示肌纤维中有泛素阳性物质沉积.mtDNA突变分析未见线粒体DNA突变.结论 伴有破碎红纤维的包涵体肌炎以近端肌肉受损为著,病理表现除包涵体和炎症性改变外,还存在代谢紊乱和异常折叠的蛋白沉积的特征.     

成人型杆状体肌病二例临床病理和超微结构研究

目的 探讨成人型杆状体肌病的临床病理和超微结构特点。方法 对2例成人型杆状体肌病患者的肌肉组织病理和超微结构进行观察。结果 2例患者均以颈肌无力起病，以后四肢和躯干肌不同程度受累，无骨骼发育畸形。肌肉组织病理改变的特点为选择性I型纤维萎缩，改良Gomori三色法染色可见萎缩纤维内含大量深紫色颗粒状物。例1发现大量中央核纤维。电镜观察可见肌原纤维排列紊乱，大量杆状体形成。在例1的肌核内发现核内包涵体，结构特点与胞质内的杆状体相似。结论 成人型杆状体肌病临床缺乏特征性。肌肉病理中央核可与杆状体同时出现，与婴儿型和儿童型杆状体肌病相比，成人型患者肌纤维萎缩明显。肌核内可出现包涵体，其结构与胞质内杆状体一致。     

包涵体肌炎11例临床及组织病理报告

目的探讨包涵体肌炎的诊断标准.方法分析了11例包涵体肌炎病人的临床表现、组织化学.碱性刚果红染色 9例,电镜检查2例.结果全部病人均在42岁后发病,表现为远、近端肌肉力弱,2例肌电图检查显示肌源性改变,11例均有边缘着色性空泡及炎性改变,9例有淀粉样蛋白沉积物,有胞核或胞质细丝包涵体各1例.结论包涵体肌炎的所有诊断指标中,无一项有决定性或特征性,需要进行综合判断.     

Inclusion body myositis and neuromuscular diseases with rimmed vacuoles]

A retrospective study of 40 patients with various neuromuscular disorders and more than 3 muscle fibers with rimmed vacuoles has been performed. Two subgroups of patients were distinguished according to the presence or absence of inflammatory exudates. In the first group (14 patients), inflammatory exudates were observed and numerous fibers showed partial invasion. Abnormal filamentous inclusions (16-18 nm in diameter) were found by electron microscopy in muscle fibers cytoplasm and/or nuclei. The diagnosis of inclusion body myositis (IBM) was made in these cases. They presented with insidious proximal muscle weakness and were not improved by immunosuppressive therapy. Immunohistological studies demonstrated T lymphocytes predominance, only few natural killer and B lymphocytes. The number of T8 lymphocytes was high in endomysial sites while T4 were more numerous in perivascular exudates. Abnormal membranous expression of class I MHC antigens was observed on muscle fibers lying near the inflammatory exudates. In the second group of cases (26 patients), no inflammatory exudate was observed. This group of neuromuscular diseases with rimmed vacuoles was heterogeneous. In 10 cases, abnormal filamentous inclusions (16-18 nm in diameter) were observed in rimmed vacuoles. However, this ultrastructural feature did not help in distinguishing subgroups. Various neuromuscular disorders were observed in this group: oculopharyngeal muscular dystrophy (12 cases with IBM like filaments in 4 cases), chronic spinal atrophy (5 cases with IBM like filaments in 3 cases), post poliomyelitis syndrome (2 cases with IBM-like filaments in one), muscle glycogenosis with IBM like filaments (2 cases), hereditary limb girdle myopathy or distal myopathy (3 cases) and 1 patient clinically presenting with polymyositis and another with cramps and myalgias. No abnormal sarcolemmal expression of class I MHC was found in this group. The pathogenesis of IBM is discussed. Besides T cell mediated cytotoxicity, denervation may be involved. The nature of the abnormal 16-18 nm filamentous inclusions remains unknown. These filaments are not IBM specific.     

眼、咽型肌营养不良的临床及病理特点分析

目的探讨眼、咽型肌营养不良的临床、组织化学染色及电镜病理特点。方法对临床诊断的3例眼、咽型肌营养不良行骨骼肌活检、组化染色、光镜、电镜分析。结果临床特点:眼睑下垂、咽下困难、构音障碍,可累及四肢骨骼肌出现肌无力、肌萎缩;光镜下病理表现:肌纤维直径大小不一,仅见少量变性、坏死、再生肌纤维,间质组织增生,小角化肌纤维散在,部分肌纤维内存在边缘空泡。电镜:边缘空泡为髓磷脂小体和吞噬空泡。结论骨骼肌活检是确诊眼、咽型肌营养不良的可靠方法。     

Les différentes formes des inclusions nucléaires et cytoplasmiques de la leucoencéphalite sclérosante subaiguë en microscopie ultrastructurale

Summary Enzyme histochemical as well as electron microscopic studies were made in a typical case of SSLE. From the enzyme histochemical point of view the lesions were not specific, and the observed increase of oxydative enzymes is identical with that found in every reactive macro- and microgliosis. No intranuclear inclusions of microtubuli with a diameter of 170–230 Å resembling certain mixoviruses could be demonstrated by electron microscopy. By light microscopy, nuclear inclusions of the Cowdry type could not be demonstrated neither; however, they are not always found in SSLE. The microtubuli inclusions, observed for the first time by one of us, seem to be the most specific element in SSLE. On the other hand, the intracytoplasmatical particles with a virus-like aspect which have been described byGonatas in SSLE and by ourselves in periaxial diffuse encephalitis of the Schilder type were also found in the present case. Our impression is that these particles are nonspecific and great caution has to take place in classifying them as viral elements. They might be secretory granules arising in the glia in certain pathological conditions, or perhaps phagocyted particles, possibly stemming from myelin.

Ce travail a été réalisé en partie grâce aux subsides de la Fondation de Recherche Scientifique Nationale de Belgique et de la Fondation Engels Born pour l'Histochimie.     

Nuclear membrane proteins are present within rimmed vacuoles in inclusion-body myositis

The rimmed vacuoles within muscle in inclusion-body myositis (IBM) are structures of uncertain origin. Two hypotheses have been proposed for their formation: that they develop as a consequence of abnormal lysosomal function or in association with the breakdown of myonuclei. We tested the latter hypothesis by studying muscle samples from 14 patients with IBM and 18 controls using immunohistochemistry for nuclear membrane proteins, examining semithin sections, and performing electron microscopy. We found that in IBM muscle vacuoles were immunoreactive for the inner nuclear membrane proteins emerin and lamin A/C. Myonuclei with fragmented or focally absent nuclear membranes were present in immunohistochemical and electron microscopy studies. The association of nuclear membrane proteins with rimmed vacuoles confirms the hypotheses that rimmed vacuoles in IBM form in association with myonuclear pathology and that IBM differs from other inflammatory myopathies in that abnormalities of myonuclei are more prominent.     

Nuclear inclusions in innervated cultured muscle fibers from patients with oculopharyngeal muscular dystrophy

We established monolayer muscle fiber cultures from muscle biopsies of 3 patients with oculopharyngeal muscular dystrophy (OPMD) who had characteristic intranuclear inclusions (INI-A) in their muscle fibers. Aneural cultures had normal morphology, except for a few muscle fibers that contained small vacuoles. Innervated cultures had large cytoplasmic vacuoles in a number of muscle fibers. Those muscle fibers were breaking easily, and could not be maintained longer than 2 months. Electron microscopy showed unusual intranuclear inclusions (INI-B) not previously reported in aneurally cultured muscle fibers of OPMD or in any normal or disease-control aneural or innervated cultured human muscle fibers. They resembled, but were not identical to, the INI-A, and they occurred in both the cultured fibers and the original muscle biopsies of all 3 patients. Our study demonstrate that (1) nuclear inclusions in OPMD reflect an intrinsic genetic defect; and (2) neuronal influence, advanced maturation, or both, seem to be essential for their induction in muscle fibers.     

眼咽型肌营养不良汉族六家系的临床和遗传学特点

目的 初步总结我国汉族眼咽型肌营养不良(OPMD)患者的临床和多腺苷酸结合蛋白核1(PABPN1)基因改变特点.方法 6个OPMD家系共28例患者,男性13例,女性15例,发病年龄32～70岁,平均发病年龄49.7岁.在可确定首发症状的患者中,以吞咽困难或构音障碍首发的13例、眼睑下垂首发的4例、双下肢无力首发的1例.经过3～20年均出现眼睑下垂、吞咽困难和构音障碍,其中7例出现四肢近端无力.对6例先证者做肌肉活体组织检查,标本进行常规组织病理和电镜检查.对6个家系的先证者以及部分家庭成员进行PABPN1基因检查,并对6例先证者进行单体型分析.结果 6例先证者的肌肉活体组织检查均发现肌纤维直径轻度变异加大伴随肌纤维内镶边空泡形成,4例患者经电镜检查发现OPMD典型的核内栅栏样丝状包涵体.3个家系的PABPN1基因型为(GCG)9,另外3个家系的基因型分别为(GCG)6(GCA)1(GCG)3、(GCG)10和(GCG)8.2个携带(GCG)9突变的家系存在rs2239579(C)-(GCG)9-SNP2622(C)的单倍体型.结论 吞咽异常和眼睑下垂均是我国汉族OPMD患者的首发症状.肌纤维出现镶边空泡以及核内包涵体是我国患者的常见病理改变.PABPN1基因的(GCG)异常扩增和(GCA)插入突变均出现在我国患者,起源具有多源性.携带(GCG)9突变的部分家系可能来自共同祖先.     

Congenital myopathy with tubular aggregates and tubulofilamentous IBM-type inclusions

We report on a 16-year-old girl with a unique neuromuscular disorder characterised by progressive proximal muscle weakness and numerous tubular aggregates, intracytoplasmic, as well as intranuclear inclusions of the IBM type in her muscle biopsy. The clinical features of the presented case, as manifested by the early childhood onset of the disease, proximal weakness, lumbar hyperlordosis, and bilateral Achilles tendon contractures, were suggestive of congenital myopathy. To the best of our knowledge, the coexistence of tubular aggregates and tubulofilamentous inclusions of the IBM type in a child has never been described.     

Acute alcoholic myopathy. Enzyme histochemistry and electron microscopic findings

Five cases of acute alcoholic myopathy were studied by light microscopy and histochemical techniques. Three cases were studied by electron microscopy. The findings were uniform showing rhabdomyolysis and chronic interstitial inflammation. Type I fibers were predominantly affected with patchy loss of oxidative enzyme activity in some fibers.The electron microscopic observations disclosed conspicuous mitochondrial abnormalities, characterized by partial or total dissolution of mitochondria with disorganization and swelling of the cristae. Bizarre paracrystalline rectangular inclusions as well as amorphous osmiophilic inclusions were noted in some degenerating mitochondria. It was concluded that such enzyme histochemical and mitochondrial changes form a non-specific response to a variety of agents injurious to skeletal muscle.     

Apoptotic muscle fiber degeneration in distal myopathy with rimmed vacuoles

Rimmed vacuole formation, tubulofilamentous nuclear inclusions and muscle fiber atrophy are the characteristic pathological findings in distal myopathy with rimmed vacuoles (DMRV). Necrotic muscle fibers were few in number and did not appear to account for the muscle weakness, but the nuclear changes with myofibrillar degeneration followed by rimmed vacuole formation appeared to be the major reason for the muscle fiber atrophy in DMRV. To determine whether the nuclear change in DMRV was related to apoptosis, we examined 15 muscle biopsy specimens immunohistochemically, and 7 of them ultrastructurally. The characteristic tubulofilamentous nuclear inclusions were found in 4 and the typical fragmented apoptotic nuclei in 3 of the 7 muscle biopsy samples examined by electron microscopy. TUNEL-positive nuclei reflecting apoptotic DNA fragmentation were found in 13 of 15 biopsies ranging from a few to approximately 1.5% of myonuclei. Apoptosis-specific protein was expressed in the sarcoplasm of atrophic fibers in 13 biopsies both with or without rimmed vacuoles. These findings suggest that the apoptotic process plays a crucial role in myofibrillar degeneration followed by autophagocytosis, i.e., rimmed vacuole formation, in DMRV.