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。     

Ezrin蛋白在肌病患者骨骼肌中的表达及意义

目的 研究Ezrin蛋白在肌病患者骨骼肌中的表达及意义.方法 取肌纤维再生活跃的假肥大型肌营养不良(DMD,9例)和多发性肌炎(PM,5例)患者的骨骼肌标本,冰冻连续切片,进行HE染色及抗-Ezrin、抗-神经细胞黏附分子(NCAM)单克隆抗体免疫组化染色,观察被检肌的病理改变和Ezrin蛋白的表达.结果 DMD、PM患者被检肌HE染色所见再生肌纤维直径较小、核位于中央、胞浆嗜碱性;NCAM染色再生肌纤维深染;再生肌纤维Ezrin呈阳性表达,伴随肌纤维成熟Ezrin表达逐渐减弱,成熟肌纤维无Ezrin表达;成肌细胞Ezrin呈阳性表达.结论 Ezrin蛋白与DMD、PM肌病患者骨骼肌纤维再生可能存在密切关系.     

强直性肌营养不良症19例骨骼肌病理分析

目的探讨强直性肌营养不良症(DM)骨骼肌病变的病理学特点。方法选择19例经临床和肌电图确诊的强直性肌营养不良症患者为研究对象,骨骼肌标本采用恒冷冰冻切片和酶组织化学染色方法,在光镜下观察骨骼肌组织的病理学变化特点。结果在HE染色,19例患者的骨骼肌标本均可见不同程度的肌纤维萎缩,但变性坏死肌纤维较少见,有7例患者在肌纤维中可见到肌质块。在组织化学MGT染色中,6例患者肌纤维中可见数量不等的破碎红边纤维(RRF),肌质块在MGT染色上呈深绿色,在NADH染色中肌质块呈深蓝色,较HE染色更易识别。在ATP酶染色中,19例患者有11例存在Ⅰ、Ⅱ型肌纤维分布异常现象,其中9例以Ⅰ型纤维明显占优势,2例以Ⅱ型纤维稍占优势,8例患者肌纤维分布基本正常。结论强直性肌营养不良症的骨骼肌病理改变,除常见的肌核增多内移,肌核聚集成核袋及核链现象以外,肌质块的出现和Ⅰ、Ⅱ型肌纤维分布异常应视为强直性肌营养不良症重要的特征性病理改变,肌肉活检对本病的诊断与鉴别诊断有一定的临床意义。     

运动神经元病临床与骨骼肌病理112例诊断分析

目的探讨骨骼肌病理对运动神经元病诊断与鉴别诊断的价值。方法收集112例运动神经元病患者的临床、神经电生理及活检骨骼肌病理资料,进行诊断与鉴别诊断分析。结果①入选患者均有肢体无力、肌萎缩,吞咽或呼吸肌无力43例,舌肌萎缩或纤颤50例,伴有肌束震颤69例,初诊伴有上运动神经元受损征78例;②肌电图呈神经源性异常;③临床确诊肌萎缩侧索硬化(ALS)90例(初诊78例、复诊/随访后12例),脊髓性肌萎缩症(SMA)22例,其中肯尼迪病7例;④骨骼肌病理均符合神经源肌病改变,ALS多见小角化肌纤维、核聚集、靶纤维;成人型SMA以小圆形肌纤维在肌束内小群分布为特点,其中肯尼迪病萎缩小圆形肌纤维、核聚集多在肌束间分布。结论①仅表现下运动神经元受累的MND,行骨骼肌活检病理分析有助ALS与SMA的诊断与鉴别诊断;②随诊、动态观察体征与病情进展变化可助ALS确诊。     

淀粉样肌病:一种难以诊断的疾病

淀粉样变性常累及多器官,包括肾、皮肤、周围神经、关节、心脏及骨骼肌,患者很少表现出肌病症状,加之既往肌肉淀粉样沉积物的组织染色检出率很低。因此,淀粉样肌病往往被漏诊。本文作者采用改良的刚果红荧光染色、免疫组化、TUNEL检测及载脂蛋白E(ApoE)基因型分析对存在肌无力症状的成年患者的肌活检标本进行了研究。 患者人选标准:(1)有肌无力症状;(2)在肌活检前没有淀粉样变性的临床依据;(3)肌标本有细胞外淀粉样沉积物。所有标本经碱性刚果红染色后,在偏振光镜和诺丹明荧光显微镜下均有嗜刚果红淀粉样沉积物浸润并包绕在血管和肌纤维周围。电镜下显示淀粉样     

Turner综合征合并抗肌萎缩蛋白病的临床表现及病理学改变

目的 探讨Turner综合征合并抗肌萎缩蛋白病（dystrophinopathy）的临床表现、病理学特点。方法 开放式骨骼肌活检,组化染色、免疫组化染色,病理分析。结果 HE染色显示中度肌萎缩,萎缩肌纤维多呈圆形,偶见坏死肌纤维,散在不透明纤维,肌间结缔组织轻度增生。抗Dystrophin-N,-C,-R单克隆抗体染色肌纤维膜淡染。结论 此文报道的患者可能为携带dystrophin缺陷基因的Turner综合征患者,因其缺少1条正常X染色体的补偿作用而出现抗肌萎缩蛋白病表现。     

杆状体肌病二例并文献复习

目的 探讨杆状体肌病的临床表现和病理特点。方法 分析2例经肌肉活检确诊的杆状体肌病患者的临床和组织病理学特点并复习文献。活检组织常规行HE、MGT、NADH-TR、SDH、NSE、ORO、PAS和ATP染色及超微结构观察。结果 先天性杆状体肌病者属于该病经典型,具有典型的四肢近端无力和肌张力低,伴高足弓畸形;成人起病者可无典型肌病表现。2例患者肌肉病理检查均可见I型纤维占优势,改良Gomori染色可见肌膜下大量蓝紫色粗颗粒样或杆状物质,部分肌纤维萎缩;1例电镜下可见部分肌纤维膜下、肌核旁多个与Z线电子密度一致的杆状小体。结论 成年起病的杆状体肌病临床表现具较大异质性。     

多轴空病四例临床与病理特点

目的探讨多轴空病患者的临床与病理特点。方法通过4例病理确诊的多轴空患者来分析本病的临床特征和病理特点。结果 4例患者肌酸激酶正常。EMG均为肌源性损害,神经传导速度正常。肌组织组化染色发现肌纤维部分萎缩,NADH-TR染色和SDH染色可见大量肌纤维内多个大小不一的氧化酶片状缺失,呈现多轴空样改变。ATP酶染色I型纤维占优势。电镜见肌纤维中央或肌膜下多个圆形无结构病灶、肌节消失、肌原纤维紊乱、线粒体、糖原减少。结论多轴空病患者发病年龄早,经典型临床以运动发育迟缓为主要特点,无呼吸功能受累者预后相对良好。肌肉组织化学染色与电镜检查是简单有效的诊断方法。     

青少年型皮肌炎的病理特点(附6例报告)

目的 探讨青少年型皮肌炎的皮肤和骨骼肌微血管病理改变规律。方法 6例患儿的发病年龄在7～14岁之间，主要表现为急性或亚急性起病的四肢肌肉无力，伴随面部和颈部皮肤水纹样皮疹。对所有患者的肌肉进行活检，其中2例患者进行皮肤活检，肌肉标本进行常规组织学和酶组织化学染色，皮肤和肌肉标本进行电镜检查。结果 6例患者均存在典型皮肌炎的肌肉病理改变特点，表现为以肌束衣为主的炎细胞浸润和束周分布的肌纤维空泡变性和再生现象。非特异性酯酶染色显示小血管和毛细血管内皮细胞深染。电镜检查发现皮肤毛细血管内皮细胞坏死消失后残留的基底膜结构和细胞降解产物，在部分成熟毛细血管内皮细胞的胞浆内可见管网包涵体，该包涵体不出现在小血管坏死和再生的内皮细胞以及平滑肌细胞内。相同改变规律的微血管病变也出现在骨骼肌内。结论 皮肤具有和骨骼肌相同的微血管病理改变规律。内皮细胞损伤是青少年型皮肌炎微血管病的主要病理改变。显然青少年型皮肌炎是血管内皮细胞病。束周肌纤维病变为继发于微血管内皮细胞病变的缺血性损伤。     

脂质沉积性肌病的临床及病理分析

目的回顾性分析脂质沉积性肌病(lipid storage myopathy,LSM)的临床及病理特点,提高临床中脂质沉积性肌病的诊断率,有助于治疗。方法对15例临床上确诊的脂质沉积性肌病患者从临床、病理特点及治疗方面进行分析。结果脂质沉积性肌病是脂肪酸氧化代谢障碍性疾病,临床主要表现为疲劳性肌无力,以近端肌肉为主(14例);激酶均有不同程度升高(15例);肌电图上呈肌源性损害(13例);抗线粒体抗体(AMA)免疫组化染色还可见到受损肌纤维内大量线粒体聚集;电镜下可见脂肪滴成串堆积在骨骼肌纤维中。结论脂质沉积性肌病在诊断上主要依靠临床、病理特点及生化检测;激素及维生素治疗可能有效。     

Hind limb muscle atrophy precedes cerebral neuronal degeneration in G93A-SOD1 mouse model of amyotrophic lateral sclerosis: a longitudinal MRI study

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disorder caused by the degeneration of motor neurons in the CNS, which results in complete paralysis of skeletal muscles. Recent experimental studies have suggested that the disease could initiate in skeletal muscle, rather than in the motor neurons. To establish the timeframe of motor neuron degeneration in relation to muscle atrophy in motor neuron disease, we have used MRI to monitor changes throughout disease in brain and skeletal muscle of G93A-SOD1 mice, a purported model of ALS. Longitudinal MRI examination of the same animals indicated that muscle volume in the G93A-SOD1 mice was significantly reduced from as early as week 8 of life, 4 weeks prior to clinical onset. Progressive muscle atrophy from week 8 onwards was confirmed by histological analysis. In contrast, brain MRI indicated that neurodegeneration occurs later in G93A-SOD1 mice, with hyperintensity MRI signals detected only at weeks 10–18. Neurodegenerative changes were observed only in the motor nuclei areas of the brainstem; MRI changes indicative of neurodegeneration were not detected in the motor cortex where first motor neurons originate, even at the late disease stage. This longitudinal MRI study establishes unequivocally that, in the experimental murine model of ALS, muscle degeneration occurs before any evidence of neurodegeneration and clinical signs, supporting the postulate that motor neuron disease can initiate from muscle damage and result from retrograde dying-back of the motor neurons.     

Muscle Computed Tomography Features of Motor Neuron Disease in Late-Onset GM2 Gangliosidosis

Late-onset GM, gangliosidosis, a rare inherited neuronal storage disease, is characterized by a vanety of clinical manifestations. The common clinical picture comprises neuromuscular, spinocerebellar, extrapyramidal, cognitive, and psychiatric abnormalities. Details of the extent of muscle involvement have never been reported. Eight patients with this syndrome were evaluated for the existence and extent of motor neuron disease using routine electrodiagnosis and systematic evaluation of skeletal musculature by computed tomography. Motor neuron disease was present in each and every patient regardless of the clmical manifestations and to a degree beyond that suspected on neurological examination. Muscle imaging disclosed a diffuse wasting and fatty replacement of muscles with predilection of pelvic and thigh muscles, and especially the quadriceps group. It seems that progressive motor disability in this syndrome IS mainly due to motor neuron disease, as manifested by muscle atrophy, which can be easily demonstrated by muscle computed tomography.     

Muscle ciliary neurotrophic factor receptor α promotes axonal regeneration and functional recovery following peripheral nerve lesion

Ciliary neurotrophic factor (CNTF) administration maintains, protects, and promotes the regeneration of both motor neurons (MNs) and skeletal muscle in a wide variety of models. Expression of CNTF receptor α (CNTFRα), an essential CNTF receptor component, is greatly increased in skeletal muscle following neuromuscular insult. Together the data suggest that muscle CNTFRα may contribute to neuromuscular maintenance, protection, and/or regeneration in vivo. To directly address the role of muscle CNTFRα, we selectively‐depleted it in vivo by using a “floxed” CNTFRα mouse line and a gene construct (mlc1f‐Cre) that drives the expression of Cre specifically in skeletal muscle. The resulting mice were challenged with sciatic nerve crush. Counting of nerve axons and retrograde tracing of MNs indicated that muscle CNTFRα contributes to MN axonal regeneration across the lesion site. Walking track analysis indicated that muscle CNTFRα is also required for normal recovery of motor function. However, the same muscle CNTFRα depletion unexpectedly had no detected effect on the maintenance or regeneration of the muscle itself, even though exogenous CNTF has been shown to affect these functions. Similarly, MN survival and lesion‐induced terminal sprouting were unaffected. Therefore, muscle CNTFRα is an interesting new example of a muscle growth factor receptor that, in vivo under physiological conditions, contributes much more to neuronal regeneration than to the maintenance or regeneration of the muscle itself. This novel form of muscle–neuron interaction also has implications in the therapeutic targeting of the neuromuscular system in MN disorders and following nerve injury. J. Comp. Neurol. 521: 2947–2965, 2013. © 2013 Wiley Periodicals, Inc.     

Spinal and bulbar muscular atrophy: skeletal muscle pathology in male patients and heterozygous females

Spinal and bulbar muscular atrophy (SBMA) is an adult form of X-linked motor neuron disease caused by an expansion of a CAG repeat sequence in the first exon of the androgen receptor (AR) gene. Nuclear accumulation of mutant AR with expanded polyglutamines in motor neurons is a major pathogenic mechanism. To characterize muscle involvement in SBMA the skeletal muscle biopsies of 8 SBMA patients and 3 female carriers were studied. Six of 8 SBMA patients showed myogenic changes together with the neurogenic atrophy in their muscle biopsy. Myopathic abnormalities did not correlate with disease duration and were more prominent in the muscle of patients with an higher degree of disability. In all patients plasma CK levels were more elevated than what usually occurs in denervative diseases. Both neurogenic and myopathic changes were also observed in female carriers. Here we suggest that myopathic changes in SBMA muscle are not only related to denervation and that muscle satellite cells may have a role in the pathogenesis of muscle damage.     

Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease leading to motor neuron cell death, but recent studies suggest that non-neuronal cells may contribute to the pathological mechanisms involved. Myostatin is a negative regulator of muscle growth whose function can be inhibited using neutralizing antibodies. In this study, we used transgenic mouse and rat models of ALS to test whether treatment with anti-myostatin antibody slows muscle atrophy, motor neuron loss, or disease onset and progression. Significant increases in muscle mass and strength were observed in myostatin-antibody-treated SOD1(G93A) mice and rats prior to disease onset and during early-stage disease. By late stage disease, only diaphragm muscle remained significantly different in treated animals in comparison to untreated controls. Myostatin inhibition did not delay disease onset nor extend survival in either the SOD1(G93A) mouse or rat. Together, these results indicate that inhibition of myostatin does not protect against the onset and progression of motor neuron degenerative disease. However, the preservation of skeletal muscle during early-stage disease and improved diaphragm morphology and function maintained through late stage disease suggest that anti-myostatin therapy may promote some improved muscle function in ALS.     

Influence of terminal nerve branch size on motor neuron regeneration accuracy

A necessary prerequisite for recovery of motor function following a peripheral nerve injury is the correct choice by regenerating motor neurons to reinnervate the original distal nerve branch to denervated muscle. The present studies use the mouse femoral nerve as a model system to examine factors that influence such motor neuron regeneration accuracy. We examined motor reinnervation accuracy over time in this model under two conditions: 1) when the two terminal nerve branches to either skin (cutaneous) or muscle (quadriceps) were roughly comparable in size, and 2) when the cutaneous branch was larger than the muscle branch. When the terminal nerve branches were similar in size, motor neurons initially projected equally into both branches, but over time favored the terminal muscle branch. When the cutaneous terminal nerve branch was enlarged (via transgenic technology), motor neuron projections significantly favored this inappropriate pathway during early time points of regeneration. These results suggest that regenerating motor neuron projections are not determined by inherent molecular differences between distal terminal nerve branches themselves. Rather, we propose a two-step process that shapes motor neuron reinnervation accuracy. Initial outgrowth choices made by motor axons at the transection site are proportional to the relative amount of target nerve associated with distal nerve axons that previously projected to each of the terminal nerve pathways. Secondly, the likelihood of an axon collateral from a motor neuron remaining in either terminal nerve branch is based upon the relative trophic support provided to the parent motor neuron by the competing terminal pathways and/or end-organs.     

The uptake of 3H(G)L leucine into single muscle fibers in Charcot-Marine-Tooth disease

In previous studies, the incorporation of 3H(G)L-leucine into muscles of patients with Charcot-Marie-Tooth (CMT) disease was shown to be increased in comparison with that observed in motor neuron disease (MND). To determine the cause of the increased uptake in CMT, studies of single fiber leucine incorporations have been undertaken. The results of this study indicate that the increased incorporation is into those muscle fibers which are undergoing regeneration following reinnervation. These results do not support the thesis that there is an associated myopathic process in CMT.     

Glycosaminoglycans co-administration enhance insulin-like growth factor-I neuroprotective and neuroregenerative activity in traumatic and genetic models of motor neuron disease: a review.

In this report it is shown how glycosaminoglycans and insulin-like growth factor-I (IGF-I) promote muscle reinnervation and prevent motor neuron death in experimental models of motor neuron disease. Such effect appears to be mediated by insulin-like growth factor-1. The glycosaminoglycan moiety of proteoglycans is a constituent of the basal lamina active on nerve regeneration by means of the interaction with laminin and with several growth factors. We have previously shown that supplementation by means of subcutaneous injections of glycosaminoglycans affects neuronal degeneration and regeneration. In this study we report that following neonatal lesion of the rat sciatic nerve, glycosaminoglycan treatment promoted extensor digitorum longus muscle reinnervation with consequent improvement of muscle morphology. In saline-treated rats, reinnervation was only partial and there was a marked muscle fibre atrophy, whereas, glycosaminoglycan treatment of lesioned rats increased IGF-I mRNA and protein in the reinnervated muscle, and IGF-I and insulin-like growth factor binding protein-3 plasma levels. Similarly, treatment of lesioned rats with IGF-I promoted muscle reinnervation, and prevented muscle fibre atrophy, higher levels of IGF-I in the reinnervated muscle, of IGF-I, and insulin-like growth factor binding proteins in plasma. In the wobbler mouse IGF-I and glycosaminoglycans alone promote only a partial motor neuron survival and the preservation of forelimb function decays after 3 weeks of treatment. However when glycosaminoglycans and insulin-like growth factor are administered together the motor neuron disease in the wobbler mouse is halted and there is no more loss of motor neurons.