运动神经元病患者骨骼肌纤维再生临床及病理研究

目的观察运动神经元病患者骨骼肌纤维再生临床及病理特点。方法选择经骨骼肌活检确诊为运动神经元病患者的临床资料及骨骼肌标本,将骨骼肌标本行HE染色、免疫组化染色,光镜观察肌纤维再生情况,部分留取电镜标本在电镜下观察骨骼肌纤维再生超微结构特点。结果活检骨骼肌标本在组化及免疫组化染色中未见明显再生肌纤维,电镜下观察到运动神经元病患者骨骼肌内可见静止、活化的肌卫星细胞。结论电镜下观察到运动神经元病患者肌肉内存在肌卫星细胞的活化、分裂及早期再生肌纤维。     

散发性包涵体肌炎一例报告

目的 探讨散发性包涵体肌炎临床与病理特点.方法 对1例散发性包涵体肌炎的临床表现,肌电图,肌肉活检等资料进行分析.结果 该病例根据临床表现,实验室检查,肌电图表现,肌肉病理改变确诊为散发性包涵体肌炎.结论 散发性包涵体肌炎发病机制尚未明确,临床表现缺乏特异性,肌肉病理学检查可以作为诊断散发性包涵体肌炎的金标准.     

风湿性多肌痛的骨骼肌病理改变特点

目的探讨风湿性多肌痛的临床和骨骼肌病理改变特点。方法13例老年和老年前期患者符合1979年Bird的风湿性多肌痛诊断标准，发病年龄49～78岁，平均60．3岁，主要临床表现为急性发病的四肢近端骨骼肌对称性持续性疼痛。其中5例伴37℃～38℃的低热，1例有轻微贫血，未发现颞浅动脉炎的改变。13例血沉均增快，其中10例血沉大于50mm／1h，8例C反应蛋白升高，1例正常，4例未查；9例行肌酶检查，其中2例轻度升高；7例行肌电图检查，2例可见肌源性损害，5例正常。对患者的肱二头肌进行活检，标本进行组织学染色和酶组织化学染色。结果13例患者均有Ⅱ型肌纤维的萎缩，8例肌纤维氧化酶活性出现虫蚀样改变，8例出现肌纤维内脂肪滴增多，3例可见个别不典型破碎样红肌纤维，2例小血管周围可见少量炎细胞浸润。患者经过激素治疗后症状迅速改善，血沉及C反应蛋白显著下降。结论本组患者的主要临床特点是出现对称性骨骼肌疼痛和血沉加快，多数患者存在C反应蛋白升高，而贫血和颞浅动脉炎发生率不高。骨骼肌常见病理改变为Ⅱ型肌纤维萎缩和虫蚀样氧化酶活性改变，肌纤维内脂肪滴增多和部分患者出现破碎样红肌纤维提示此病常伴随能量代谢异常。     

包涵体肌炎的临床与肌肉病理特征

包涵体肌炎在国内鲜见，兹对其临床与肌肉病理特征作一复习。报告一例包涵体肌炎老年男性患者，隐袭起病，病情缓慢进展长达２３年，临床表现以吞咽困难为首发症状，７年后出现以双侧股四头肌为主的、对称性近端肌无力和肌萎缩，胸锁乳突肌、腹肌也受累，不伴有肌痛。有类风湿性关节炎病史。肌电图示肌原性受损。血沉、肌酸激酶、免疫球蛋白Ｇ呈轻中度升高，类风湿因子阳性。肌肉活检表现为：非坏死肌纤维的单核细胞浸润，特征性的边缘着色性空泡，电镜下发现有确诊意义的胞浆内包涵体，内含大量丝状物，确认为包涵体肌炎。提示在遇有上述特征性改变的患者应想到本病。     

实验性肌炎动物模型制作的研究

目的建立实验性肌炎动物模型，研究特发性炎性肌病的发病机制。方法将50只健康的雄性SD大鼠随机分成两组：模型组40只，对照组10只。兔骨骼肌制备肌匀浆。模型组用肌匀浆与弗氏完全佐剂完全乳化后皮下免疫注射1ml．对照组用生理盐水替代肌匀浆，每周免疫1次，连续免疫5次。前2周同时腹腔注射百日咳毒素1ml。分别于免疫注射后各周取大鼠的骨骼肌组织，观察其肌活检病理、免疫组织化学的改变，同时检测血清肌酶水平，并与人类炎性肌病比较。结果模型组肌酶升高与对照组间有显著差别。病理改变以骨骼肌多发性炎症为特点：横纹肌呈灶性分布的肌纤维变性、坏死，横纹消失；周围炎性细胞浸润；肌纤维粗细不等、染色不一。病理分级以2a级为主。单个核细胞浸润以CD8^＋T细胞为主．主要定位于肌内膜。骨骼肌细胞膜上主要组织相容性复合体（MHC）-Ⅰ类分子表达增加。结论用异种动物骨骼肌匀浆免疫大鼠可诱导出炎性肌病动物模型，与人类炎性肌病在临床表现、组织病理和免疫组织化学方面有相似之处。     

抗信号识别颗粒抗体肌病八例临床分析

目的 总结抗信号识别颗粒抗体肌病患者的临床和骨骼肌病理改变特点.方法 选择8例患者采取免疫印迹法测定血清肌炎抗体谱并进行肌肉活检,肌肉标本进行组织学、酶组织化学和免疫组织化学染色.免疫组织化学染色的第一抗体为鼠抗人CD8、CD20、CD68单克隆抗体,分别标记T细胞、B细胞和巨噬细胞,主要组织相容性复合体(MHC)-Ⅰ单克隆抗体标记肌纤维膜,CD31单克隆抗体标记毛细血管内皮细胞.结果 8例患者血清抗信号识别颗粒抗体均为强阳性,其中3例伴随Ro-52抗体阳性.8例患者骨骼肌出现肌纤维坏死、再生以及巨噬细胞浸润,2例患者伴随肌纤维肥大和间质增生,2例伴随少数T细胞浸润.存在部分MHC-Ⅰ阳性肌纤维,毛细血管密度正常.结论 抗信号识别颗粒抗体肌病以缓慢发病的肢体无力为主要表现,可伴肺部病变.肌纤维坏死、再生为其主要病理改变,可以类似肌营养不良改变.     

Ezrin蛋白在老年多发性肌炎患者骨骼肌中的表达

目的探讨Ezrin蛋白在老年多发性肌炎患者骨骼肌中的表达。方法选取12例老年多发性肌炎患者骨骼肌标本,冰冻连续切片,HE及酸性磷酸酶组织化学染色;抗-Ezrin蛋白单克隆抗体免疫组织化学染色,对比观察同源肌纤维染色情况。结果 Ezrin蛋白在炎性细胞浸润的血管周围及肌间隙内呈阳性表达,在正常肌纤维上表达不明显。结论 Ezrin蛋白在老年多发性肌炎患者骨骼肌中与炎性反应关系密切。     

低肌病性皮肌炎的临床和肌肉病理特点六例分析

目的 了解低肌病性皮肌炎的临床表现和肌肉病理改变特点.方法 收集我院2008年1月至2010年6月行肌肉活检的62例皮肌炎患者,按照低肌病性皮肌炎的诊断标准筛选6例,其中4例患者肌电图呈肌源性损害.同时对6例患者进行肱二头肌活检,标本进行组织学、酶组织化学染色和免疫组织化学染色,后者的第一抗体分别为CD8、CD20和CD68鼠抗人单克隆抗体以及标记主要组织相容性复合物Ⅰ型抗原(MHC-Ⅰ)的鼠抗人单克隆抗体.结果 6例患者的肌纤维内脂肪滴均有轻至中度增多,肌束衣出现个别巨噬细胞浸润和B淋巴细胞浸润.3例患者出现个别小圆状萎缩肌纤维呈束周分布的特点,伴随个别肌纤维的坏死再生.所有患者束周分布的肌纤维膜存在MHC-Ⅰ深染,束周分布的肌间毛细血管非特异性酯酶深染.结论 部分低肌病性皮肌炎患者的骨骼肌病理改变类似经典皮肌炎,提示此病可能是单纯无肌病皮肌炎和经典皮肌炎的中间型.     

特发性炎性肌病的分子病理研究进展

特发性炎性肌病(IIM)是一组临床特点、病理表现和治疗预后各异的自身免疫性疾病。主要临床表现为肌无力,也可影响包括皮肤、关节、肺脏、心脏和消化道等多个骨骼肌外系统和器官,有些IIM的亚型甚至以肌外系统损害为主要表现。近年来发现了多种肌炎特异性抗体与IIM密切相关,不同抗体相关的临床表型、病理改变和对治疗的反应均各不相同,提示存在不同的病理生理机制。目前比较公认基于临床-病理-血清学特点,将IIM进一步分为皮肌炎、抗合成酶抗体综合征、免疫介导坏死性肌病、包涵体肌炎和多发性肌炎这几种亚型。本文介绍了IIM各亚型的分子病理研究的最新进展,以期为临床和病理医生提供参考。     

特发性炎性肌病119例肌肉活检病理分析

目的：探讨特发性炎性肌病（IM）的肌肉活检病理类型及其临床病理联系。方法：回顾性分析IM的病理改变，归纳出各病理类型的特点，随访并评估IM患者的预后情况。结果：在119例IM中，重、中、轻度坏死性肌炎分别为11例、19例和27例，束周坏死／萎缩性肌炎20例，无炎细胞浸润的坏死性肌炎22例，间质性肌炎11例，肌筋膜炎3例，包涵体肌炎4例，肉芽肿性肌炎和增生性肌炎各1例，其中72例获得随访资料，轻度坏死性肌炎和束周坏死／萎缩性肌炎患者的好转和治愈的百分比高于中，重度坏死性肌炎患者，间质性肌炎和无炎细胞浸润的坏死性肌炎的好转和治愈百分比高于重度坏死性肌炎，结论：IM的病理类型对判断预后具有重要的参考价值。     

Familial inflammatory inclusion body myositis

OBJECTIVE: To compare familial inflammatory inclusion body myositis (IBM) with hereditary inclusion body myopathies and sporadic IBM. PATIENTS AND METHODS: Clinical, biological, MRI, and histological data were analysed in two siblings with inflammatory IBM and compared with those of patients with sporadic and hereditary IBM. RESULTS: Both patients had a clinical phenotype of sporadic IBM, which differs from hereditary myopathies because of late age of onset--respectively 65 and 66 years, and different pattern of muscular involvement--asymmetric, mainly distal but also involving quadriceps. MRI showed selective fatty infiltration and oedema in the extensor compartment of thigh muscles. The diagnosis of IBM was confirmed by muscle biopsy, showing muscle fibres containing numerous rimmed vacuoles, a characteristic shared by all types of IBM. In contrast with hereditary IBM, histological analysis also showed inflammatory mononuclear infiltrate invading non-necrotic fibres, ragged red and oxidase c negative fibres, and positive Congo red staining. Moreover, HLA class II typing disclosed DR beta 1 0301 haplotype, which is significantly related to sporadic but not to hereditary IBM. With steroid treatment and monthly intravenous immunoglobulins, the disease was stabilised in both patients at protracted follow up. CONCLUSION: Sporadic and familial inflammatory IBM share the same clinical, biological, MRI, and histological features.     

Inclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscle

Inclusion body myositis (IBM), the most common age-related muscle disease in the elderly population, is an incurable disorder leading to severe disability. Sporadic IBM has an unknown etiology, although affected muscle fibers are characterized by many of the pathobiochemical alterations traditionally associated with neurodegenerative brain disorders such as Alzheimer's disease. Accumulation of the amyloid-beta peptide, which is derived from proteolysis of the larger amyloid-beta precursor protein (betaAPP), seems to be an early pathological event in Alzheimer's disease and also in IBM, where in the latter, it predominantly occurs intracellularly within affected myofibers. To elucidate the possible role of betaAPP mismetabolism in the pathogenesis of IBM, transgenic mice were derived in which we selectively targeted betaAPP overexpression to skeletal muscle by using the muscle creatine kinase promoter. Here we report that older (>10 months) transgenic mice exhibit intracellular immunoreactivity to betaAPP and its proteolytic derivatives in skeletal muscle. In this transgenic model, selective overexpression of betaAPP leads to the development of a subset of other histopathological and clinical features characteristic of IBM, including centric nuclei, inflammation, and deficiencies in motor performance. These results are consistent with a pathogenic role for betaAPP mismetabolism in human IBM.     

Muscle biopsy findings in inflammatory myopathies

The inflammatory myopathies encompass a heterogeneous group of acquired muscle diseases characterized clinically, by muscle weakness, and histologically, by inflammatory infiltrates within the skeletal muscles. The group of these myopathies comprise three major and discrete subsets: polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). Each subset retains its characteristic clinical, immunopathologic, and morphologic features regardless of whether it occurs separately or in connection with other systemic diseases. Although the diagnosis of these disorders is based on the combination of clinical examination, electromyographic data, serum muscle enzyme levels, various autoantibodies, and the muscle biopsy findings, the muscle biopsy offers the most definitive diagnostic information in the majority of the cases. This article summarizes the main histologic features that characterize PM, DM, or IBM and emphasizes the main pitfalls associated with interpretation of the biopsies.     

Histological data in inflammatory myositis

Inflammatory muscular diseases of adult and child consist of dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). Muscular biopsy takes a seminal place in their diagnosis, through analysis of the topography and clustering of individual histological lesions: endomysial, perimysial and perivascular inflammation, muscular necrosis with regeneration, fibre modifications, fibrosis, micro-angiopathy. They can be associated with collagen diseases or malignant tumors that usually precede them. IBM seems somewhat apart among inflammatory myopathies, being characterised by the association of neurogenic and myogenic features and the presence of vacuoles containing filaments with an accumulation of proteins previously reported in Alzheimer's disease (beta amyloid protein, tau, ubiquitin,.). Inflammation is of various intensity, lacking in familial IBM (hereditary inclusion body myopathy) that otherwise shares the same histologic characteristics as sporadic forms. Other inflammatory muscular diseases: focal myositis, eosinophilic polymyositis, are less frequent. Macrophagic myofasciitis, viral myositis and drug induced myositis are discussed in other articles.     

Morphological and clinical aspects of Danon disease

BACKGROUND: Danon disease, an X-linked hypertrophic cardiomyopathy, is caused by primary deficiency of lysosome-associated membrane protein (LAMP-2). The pathological hallmark of the disease is the appearance of intracytoplasmic vacuoles containing autophagic material and the absence of LAMP-2 activity in the muscle. AIM: To define the LAMP-2 protein deficiency we investigated cardiac and skeletal muscle of a 19-year-old man with hypertrophic cardiomyopathy without clinically apparent skeletal myopathy or mental impairment, whose mother died suddenly at 46 years of age. METHODS: Clinical, morphological, immunohistochemical and ultrastructural analysis was performed. Paraffin sections of cardiac muscle were stained using routine histochemical methods. Frozen sections of skeletal muscle were stained using histochemical methods as well as using monoclonal antisera against N-terminal of dystrophin and antisera against LAMP-2. Ultrastructural examination of both cardiac and skeletal muscle specimens were performed. RESULTS: Cardiac and skeletal muscle revealed an excessive accumulation of early and late autophagic vacuoles containing various cytoplasmic debris. In immunohistochemical analysis the vacuolar membrane seen in skeletal muscle was decorated with antibody against dystrophin and such vacuoles were negative for LAMP-2. CONCLUSION: Ultrastructural and immunohistochemical analysis of skeletal muscle (less invasive than myocardial biopsy) may be used in diagnosis of Danon disease. Early diagnosis of Danon disease is important for timely cardiac transplantation, the only effective therapeutic option.     

Pathogenesis of the idiopathic inflammatory myopathies

The inflammatory myopathies, commonly described as idiopathic, are a group of acquired diseases characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical and immuno-pathological features, three major diseases can be identified: dermatomiositis (DM), polymyositis (PM) and inclusion body myositis (IBM). Immunopathogenesis mechanisms are crucial for discriminating between the three different subsets of inflammatory myopathies. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens. This article summarizes the main immunopathological markers. The impact of this new knowledge must be defined in relation to potential therapeutic targets for idiopathic inflammatory myopathies.     

New classifications and pathophysiology of the inflammatory myopathies

SCOPE: Review on new classifications of myositis linked with their different pathophysiology. CURRENT SITUATION AND SALIENT POINTS: The classification of myositis refined recently, taking into account clinical (such as isolated muscle involvement or not, association with cancer...), immunological (presence or absence of auto-antibodies) and pathological criteria. This new classification has the ability to separate different clinical and physiopathological entities, having actually different prognosis factors. The most common inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), but also, overlap myositis (defined, among others, by the presence of auto-antibodies), and myositis associated to cancers. These myopathies may be also distinguished by their histological features which also reflect their different underlying pathogeneses. The mechanism of DM is complement-mediated microangiopathy, the inflammatory infiltrate being secondary to ischaemic damage. In PM the muscle fibres are damaged by cytotoxic CD8 T lymphocytes. IBM may be a degenerative disease with accumulation of a variety of proteins within the fibres. The inflammatory infiltrate, which is similar to that seen in PM, may be secondary to accumulated proteins. PERSPECTIVES: These diseases with different pathogeny and prognosis should be treated by specific approaches. That is the reason why we initiated specific clinical trials for respectively inclusion body myositis and overlap myositis.     

Corticosteroid-responsive skeletal muscle disease associated with partial carnitine deficiency: studies of liver and metabolic alterations.

A patient with progressive skeletal muscle weakness had lipid-containing vacuoles in type I muscle fibers and partial carnitine deficiency of skeletal muscle. Results of certain liver function tests were abnormal, marked morphologic abnormalities of liver were detected, and a reduced cyclic adenosine 3',5'-monophosphate response to glucagon was present. After the oral administration of prednisone the patient exhibited gradual but striking clinical improvement, skeletal muscle fiber vacuoles could no longer be demonstrated, and the glucagon-provoked cyclic AMP response reverted to normal, but liver abnormalities persisted. At the same time utilization by skeletal muscle of long-chain fatty acids, pyruvate and beta-hydroxybutyrate was depressed. It is possible that the involvement of skeletal muscles was due to an inability of carnitine to attach to or to penetrate the sarcolemmal membrane. Some of the derangement, perhaps related to liver malfunction, was apparently corrected by the oral administration of prednisone although skeletal muscle metabolism remained impaired.     

肥厚型心肌病样心肌病五例及其分析

目的 探讨以左心室心肌肥厚为重要表型的非肥厚型心肌病的其他遗传性心肌病诊断线索.方法 分析临床中5例因不可解释左心室心肌肥厚初诊肥厚型心肌病而后确诊为其他遗传性心肌病患者的临床特征、生化指标、心电图和确诊方法.结果 5例患者心电图均示左心室高电压,ST-T改变.1例年轻男性伴肌无力、心室预激、丙氨酸转氨酶(ALT)、肌酸激酶(CK)持续升高,肌肉病理活检示肌纤维内含自噬和糖原空泡,诊断Danon's病.1例年轻男性,短P-R间期,肌肉活检可见破碎红纤维,诊断线粒体心肌病.3例有发作性手足痛、皮肤血管角质瘤,血白细胞α-半乳糖苷酶活性降低,诊断Fabry病.结论 因左心室心肌肥厚表现为肥厚型心肌病样的遗传性心肌病患者少见,通过仔细询问病史、临床表现特点和相关特殊检查可能明确诊断.     

老年高血压伴主动脉夹层患者临床及病理分析

目的探讨老年高血压伴主动脉夹层临床表现与病理特点。方法选择15例老年高血压伴主动脉夹层患者为夹层组,同期选择高血压未伴主动脉夹层15例患者为对照组,取入选患者的尸体解剖病理切片,回顾性分析2组临床表现、病理特点及免疫组织化学检测状况。结果与对照组比较,夹层组患者临床表现复杂多样,病理特点为夹层壁内平滑肌细胞明显退行性变,弹力纤维减少或断裂,胶原纤维增生,夹层壁内血管第八因子相关抗原表达增强,平滑肌肌动蛋白表达降低。结论高血压伴主动脉夹层是严重威胁老年人生命的一种并发症。严格控制血压,是预防老年人主动脉夹层发生的重要手段。