远端型肌病71例的临床及肌肉病理分析

目的　探讨远端型肌病的临床表现及肌肉病理特点。方法　对71例远端型肌病患者进行回顾性分析。结果　71例患者中,Nonaka型26例,呈散发或常染色体隐性遗传,多以胫前肌无力为首发症状,肌肉坏死较轻,镶边空泡(rimmedvacuole,RV)多见,可见管状细丝包涵体;Miyoshi型38例,呈散发或常染色体隐性遗传,多以腓肠肌力弱为首发症状,肌肉变性坏死严重,RV少见;TMD型2例,均为散发病例,病变主要局限于胫前肌,病情进展较慢,有肌肉变性坏死,可见RV;Welander型4例,呈散发或常染色体显性遗传,以手指、腕部无力为首发症状,可波及下肢远端,轻度肌肉变性坏死,偶可见RV;OPDM型1例,呈常染色体显性遗传,表现为下肢远端肌无力伴眼外肌、面部肌肉、咽肌无力,肌肉坏死不显著,可见RV。结论　在中国Miyoshi型、Nonaka型、TMD型、Welander型及OPDM型远端型肌病均可见到,各型临床表现及病理改变与国外报道基本一致。     

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。     

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。     

伴随痴呆、眼外肌麻痹和耳聋的包涵体肌病

包涵体肌病是一组原因不明的慢性进行性骨骼肌变性病 ,病理改变特点是肌纤维内出现嗜碱性的空泡、胞质体和类淀粉样物质 ,在电镜下发现细胞核和肌质内出现管丝包涵体[1] ,由于缺乏炎细胞浸润而不同于包涵体肌炎 ,在其 3个亚型中除Ⅲ型出现眼外肌麻痹外[2 ] ,临床表现均为进行性的四肢无力。我们报道 1例伴随痴呆、眼外肌麻痹和耳聋的包涵体肌病 ,探讨其可能的归类。资料和方法 :患者男性 ,2 3岁 ,自幼出现左视麻痹 ,10年前出现四肢无力 ,8年前出现反应迟钝 ,双耳听力下降 ,讲话声音嘶哑 ,含糊不清和饮水呛咳 ,四肢无力不能提物 ,近 3年四肢…     

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肌病临床病理及肌肉磁共振特点分析

目的探讨Nonaka肌病的临床、肌肉病理及肌肉磁共振特点。方法入选2例患者,女性1例,男性1例,临床表现均以双下肢远端肌肉无力、萎缩为主,双上肢仅轻度受累。血清肌酸激酶轻度升高,肌电图提示肌源性损害,神经传导速度均正常。对患者完善大腿及小腿肌肉磁共振检查,并予以左上肢肱二头肌活检,进行组织学、酶组织化学及免疫组织化学染色,抽取外周静脉血2mL送基因公司进行遗传性肌肉病相关基因测序。结果肌肉病理提示,肌纤维肥大、萎缩、再生,肌纤维内可见镶边空泡,符合肌病样病理改变。肌肉MRI提示,大腿股四头肌脂肪化程度较轻,尤其是股外侧肌未受累及,大腿后组肌群及小腿胫前肌、胫后肌脂肪化程度严重。基因结果均提示GNE基因突变。结论 Nonaka肌病是一种与GNE基因突变相关的常染色体隐性遗传性远端肌病,临床表现特点为胫前肌首先受累,而股四头肌早期不受累。病理改变特点为肌纤维内镶边空泡形成。肌肉MRI可提示肌肉脂肪化的程度及分布规律,为诊断提供依据。     

包涵体肌炎（附1例报告并文献复习）

报道一例包涵体肌炎患者，女，２５岁。表现为缓慢进展的两下肢无力５年，近半年两上肢亦无力。两侧肩胛带及骨盆带肌肉轻度萎缩，肌电图示轻收缩时运动电位平均时限缩短，多相电位增多。肌活检见部分肌纤维内出现空泡，在空泡的边缘或空泡内有嗜盐基性颗粒状物质，Ⅰ型、Ⅱ型肌纤维均受累。结合文献对其病因、临床表现、肌肉病理改变、诊断和治疗进行了讨论     

眼咽远端型肌病一家系的咽喉功能观察以及骨骼肌病理特点

目的 报道1个眼咽远端型肌病家系的病理和电生理改变特点,分析其吞咽功能障碍的变化规律.方法 先证者为24岁女性,出现进行性加重的眼外肌麻痹、吞咽困难、构音障碍及四肢远端无力和萎缩2年.肌酸激酶轻度升高.家族同代人中还有5例在20～30岁出现类似症状.对先证者进行纤维咽喉镜吞咽功能检查和肌电图检查,对胫前肌进行肌肉病理检查.结果 纤维咽喉镜检查发现软腭上抬差,肌电图检查发现胫前肌呈现肌源性损害伴随肌强直现象.肌肉病理改变特点是肌纤维出现肥大、萎缩、间质纤维化,部分肌纤维内可见镶边空泡,电镜检查显示肌纤维的胞质内存在管丝包涵体.结论 临床和病理检查证实眼咽远端型肌病的存在,软腭运动障碍是出现咽喉症状的主要原因,此病存在肌强直的电生理改变特点.     

散发性包涵体肌炎临床与肌肉病理特点

目的 探讨散发性包涵体肌炎(sIBM)的临床和肌肉病理特点。方法 回顾性分析5例sIBM患者的临床和肌肉病理资料。结果 本组5例患者中，男3例，女2例；发病年龄36～68岁，平均49.8岁；出现症状至确诊时间为2～12年，平均6.2年。5例患者均以双下肢无力隐匿起病，症状缓慢进展，逐渐发展为四肢无力。脑神经正常，四肢肌张力减低，腱反射减低或消失，上肢近端肌力Ⅲ～Ⅴ级，远端肌力Ⅲ～Ⅳ级；下肢近端肌力Ⅱ～Ⅴ级，远端肌力Ⅲ～Ⅳ级。5例患者均有不同程度的肌肉萎缩。EMG检查示4例呈肌源性损害，1例呈肌源性和神经源性共存的混合性损害。肌肉病理表现为肌纤维大小不等，可见萎缩和肥大肌纤维，散在有变性坏死肌纤维，伴炎性细胞浸润。5例患者均可见镶边空泡，4例可见炎性细胞侵入非坏死肌纤维现象。淋巴细胞亚群免疫组化染色可见CD8和CD68阳性淋巴细胞浸润。结论 sIBM好发于中老年人，除上肢远端指屈肌和下肢股四头肌无力以外，部分患者早期可有下肢远端肌无力。肌肉病理发现肌纤维中有镶边空泡和炎性细胞浸入非坏死肌纤维是确诊sIBM的重要依据。     

神经元核内包涵体病

神经元核内包涵体病是一种罕见的神经系统变性疾病 ,典型可见智能减退 ,锥体系、锥体外系体征如肌强直、姿位异常、静止性震颤、舞蹈样手足徐动、肌阵挛、双侧腱反射亢进、双侧Babinski征 ,下运动神经元损害 ,感觉减退。行为功能障碍 ,步态不稳、小脑性共济失调、构音障碍等小脑体征 ,神经肌肉受累如吞咽困难、弥漫性肌萎缩以及眼球运动异常等 ,神经病理可见特征性的神经元核内包涵体。病程缓慢进展 ,无有效治疗。     

The clinical and myopathological features of oculopharyngodistal myopathy in a Chinese family

Oculopharyngodistal myopathy is a rare type of hereditary myopathy characterised pathologically by the changes of muscular dystrophy with rimmed vacuoles and intra‐muscular tubulofilamentous inclusions. Here we report the clinical and myopathological changes in a Chinese family with oculopharyngodistal myopathy. The proband showed external ophthalmoplegia, dysphagia, distal weakness and atrophy in all extremities. Serum creatine kinase level was mildly elevated and a myopathic pattern with myotonic discharge was demonstrated by electromyography (EMG). Molecular genetic analysis showed that the number of trinucleotide repeat expansions in the polyadenylate‐binding protein nuclear 1 gene was within the normal limit. No mutations were indentified in the GNE gene. Five other persons with similar symptoms were found in the same generation. Muscle biopsy was performed on the tibialis anterior muscle in the proband. Muscular dystrophy changes with rimmed vacuoles were the main histopathological changes. Ultrastructural examination revealed numerous tubulofilamentous inclusions in both sarcoplasm and nucleus. EMG showed myotonic discharges in oculopharyngodistal myopathy. In addition to the sarcoplasm inclusions, we confirmed that tubulofilamentous inclusions appeared also in the nucleus.     

全身性癫癎伴高热惊厥附加症致病基因的连锁定位研究

目的　定位全身性癫癎伴高热惊厥附加症的致病基因。方法　采用全基因组扫描的连锁分析方法对全身性癫癎伴高热惊厥附加症4个家系进行研究。结果　在染色体5q34多点连锁分析显示最大LOD值为3. 815。染色体单体型分析将连锁范围缩小至D5S820至D5S1476之间4. 0厘摩(cM)的区域。结论　全身性癫癎伴高热惊厥附加症致病基因定位在染色体5q34。     

Familial inclusion body myopathy with desmin storage

We report two adult familial cases of inclusion body myopathy (IBM) with desmin storage in skeletal muscle. Clinically, both patients presented late-onset, progressive, symmetrical, both proximal and distal muscle weakness. Muscle biopsy findings were identical in both cases and consisted of marked variability in fiber size, increased number of central nuclei and vacuolation involving 10% of fibers. Single or multiple vacuoles were located subsarcolemmally or in the center, and were rimmed by basophilic material. At the ultrastructural level, tubulofilamentous nuclear and cytoplasmic inclusions of 16–21 nm in diameter were frequently observed. In addition, large subsarcolemmal and central deposits composed of electron-dense granular material were present in many fibers. Immunocytochemistry revealed staining for desmin, vimentin and ubiquitin within both inclusions and vacuolated fibers. Possible structural and functional associations between these two types of muscle changes remain unclear. They may either represent two coexistent disease processes or merely reflect an abnormal form of muscle fiber degradation, with unidentifiable specificity. Received: 30 January 1998 / Revised: 15 June 1998 / Accepted: 20 October 1998     

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.     

Reducing bodies in distal myopathy with rimmed vacuole formation

A 42-year-old woman with distal myopathy with rimmed vacuoles had intracytoplasmic inclusion bodies similar to those described in reducing body myopathy. Since these inclusions were found in fibers with high acid phosphatase activity and occasional rimmed vacuoles, their formation appeared to correlate with active myofibrillar degeneration, but their origin remains unknown.     

Increase of cytochrome c oxidase negative fibers in rimmed vacuole myopathy with inflammatory changes

The physiological significance of cytochrome c oxidase (CCO) deficiency in rimmed vacuole myopathy (RVM) is not fully understood. Frequencies of CCO negative muscle fibers (CCO(?)F) were compared with two cases of in-clusion body myositis (IBM) and another two cases with RVM without inflammatory changes (i.e. oculopharyngeal distal myopathy (OPDM) and distal myopathy with rimmed vacuole formation (DMRV)). The frequencies of CCO(?)F were 6.9% in the case of definite IBM with 10 years of disease duration, 0.3% in possible IBM of 1 year duration, 1.3% in OPDM of 11 years duration, and 0.1% in DMRV of 2 years duration. The frequencies of CCO(?)F were generally higher in RVM than in controls. However, the incidence of CCO(?)F increased with time in patients with IBM compared with patients with RVM without inflammation. The present findings may provide important information on the myopathological distinction of IBM and RVM without inflammation.     

Intranuclear and cytoplasmic filamentous inclusions in distal myopathy (Welander)

Summary Ultrastructural examination of anterior tibial muscle from four patients with late-onset autosomal dominant distal myopathy of Welander-type revealed intrasarcoplasmic filamentous inclusions in association with rimmed vacuoles. In one of the patients, identical intranuclear filamentous inclusions were also found. These filamentous inclusions are similar to those desxribed in inclusion body myositis (IBM). They have also been observed in hereditary neuromuscular disorders including autosomal recessive distal myopathy. Thus, the filamentous inclusions occur in different neuromuscular conditions with different etiologies. These findings further raise the question of the specificity of the filamentous inclusions in IBM.Supported by grants from the Swedish Medical Research Council (proj. 3875, visiting research grant K. Borg), the Swedish MS foundation, the Swedish Society of Medicine, the Swedish Society for Traffic and Polio Disabled, Erik and Edith Fernströms Foundation for Medical Research and from the Karolinska Institute