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。     

A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM

OBJECTIVE: To investigate whether the combination of intravenous immunoglobulin (IVIg) with prednisone improves muscle strength and alters endomysial inflammation in patients with sporadic inclusion body myositis (s-IBM). BACKGROUND: In a previous controlled trial in s-IBM, IVIg did not significantly improve strength in spite of modest benefits in some muscle groups. The possibility that prednisone may have a synergistic effect with IVIg prompted another controlled trial. METHODS: Thirty-six patients with biopsy-proven IBM were randomized to receive IVIg or placebo monthly for 3 months. Before infusions, all patients were started on high-dose prednisone for 3 months. Primary outcome measures were differences in the 1) Quantitative Muscle Strength (QMT) testing; and 2) modified Medical Research Council (MRC) scores, between the patients randomized to IVIg + prednisone compared with those randomized to placebo + prednisone. Repeated open muscle biopsies were performed at random in 24 patients to determine changes in the number of autoinvasive T cells and necrotic muscle fibers. RESULTS: Nineteen patients were randomized to IVIg + prednisone and 17 to placebo + prednisone. No significant change was noted in muscle strength, assessed by QMT and MRC, from baseline to the 2nd, 3rd, or 4th month after treatment between the two groups. The number of necrotic fibers was reduced in the IVIg randomized group (p < 0.01), and the mean number of CD2+ cells was significantly decreased in both groups (p < 0.0001), denoting a steroid effect. CONCLUSION: IVIg combined with prednisone for a 3-month period was not effective in IBM. Endomysial inflammation was significantly reduced after treatment, but the reduction was not of clinical significance.     

Inclusion body myositis

The clinical features of inclusion body myositis (IBM) were of minor importance in the design of consensus diagnostic criteria, mainly because of controversial views on the specificity of signs and symptoms, although some authors reported "typical" signs. To re–assess the clinical spectrum of IBM, a single investigator using a standard protocol studied a cohort of 64 patients cross–sectionally. Symptom onset was before the age of 50 years in 20% of cases. Only a few patients (14 %) started with weakness other than that of quadriceps, finger flexor or pharyngeal muscles. The sequence of power loss was erratic, but onset of symptoms with quadriceps weakness predicted an earlier onset of dysphagia in older patients (≥ 56 years) compared with younger ones (< 56 years) (p = 0.02). Despite widespread weakness patients had favourable scores on three commonly used function scales and they kept their employment. Complete wheel–chair dependency was rare (3 %). A dominant characteristic was the anatomical distribution of afflicted muscles: ventral extremity muscle groups were more affected than dorsal muscle groups and girdle muscles were least affected, the latter preserving postural stability. Ankylosis, especially in extension of the fingers,was frequently present. Together with the sparing of intrinsic hand muscles it was helpful in the preservation of many skilful movements. IBM has a unique distribution of muscle weakness. Ankylotic contractures are common. We feel that their joint impact on daily functioning is characteristic for the disease.     

Inflammatory muscle diseases

The three major immune-mediated inflammatory myopathies, dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM), each have their own distinctive clinical features, underlying pathogenetic mechanisms and patterns of muscle gene expression. In DM a complement-dependent humoral process thought to be initiated by antibodies to endothelial cells results in a microangiopathy with secondary ischemic changes in muscles. On the other hand, in PM and IBM there is a T-cell response with invasion of muscle fibers by CD8+ lymphocytes and perforin-mediated cytotoxic necrosis. In IBM degenerative changes are also a feature and comprise autophagia with rimmed vacuole formation and inclusions containing beta-amyloid and other proteins whose accumulation may be linked to impaired proteasomal function. The relationship between the inflammatory and degenerative component remains unclear, as does the basis for the selective vulnerability of certain muscles and the resistance to conventional forms of immunotherapy in most cases of IBM. Patients with DM or PM usually respond to treatment with glucocorticoids and immunosuppressive agents but their use remains largely empirical. Intravenous immunoglobulin therapy can be used to achieve disease control in patients with severe weakness or dysphagia, or in patients with immunodeficiency, but its use is limited by expense. Emerging therapies for resistant cases include TNFalpha inhibitors (etanercept, infliximab) and monoclonal antibodies (rituximab, alemtuzumab). However, experience with these therapies is still limited and there is a need for randomized trials to test their efficacy and establish guidelines for their use in clinical practice.     

Polymyositis: its presentation, morbidity and mortality.

A survey of 118 patients seen in the last twenty years in Newcastle upon Tyne forms the basis of this report. All of these 118 patients fulfilled clearly defined clinical, electrophysiological and pathological criteria for the diagnosis of polymyositis: muscle pain, weakness and characteristic EMG and/or muscle biopsy 55%; and characteristic muscle biopsy 17%; muscle weakness and characteristic EMG 7%; muscle weakness and pain, and raised serum CK activity in an established collagen-vascular disease 5%. A smaller group of 25 patients were selected in whom the clinical characteristics, EMG, muscle biopsy and serum enzyme levels were all completely diagnostic of polymyositis. The patients were followed for two months to twenty-six years, with a mean follow-up duration of six years. Analysis was made of the features at presentation and during the course of the illness, and of prognostic factors bearing upon the disability, response to treatment and mortality. Cases were classified according to the system of Rose and Walton (1966). Groups I, II, and III each constituted approximately one-third of the total cases, while only 8% of all cases were associated with carcinoma. The female to male ratio was 1.4:1. Though cases were seen in all age groups, the largest number was in the sixth decade. The sedimentation rate was raised in 55% of cases. Electromyography was characteristic of polymyositis in 45% of cases, and in only 11% was it normal. The serum creatine kinase activity was raised in 64% of cases. There was no correlation between the extent of these abnormalities and the degree of weakness or disability. 65% of muscle biopsies had changes with inflammatory infiltration virtually diagnostic of polymyositis. 17% of cases had a normal muscle biopsy. Most of the patients (89%) were treated with high-dose prednisone therapy, commencing with 30-100 mg/day, gradually reducing to a maintenance dose of 5-15 mg/day over two or three months. All clinical groups showed considerable improvement in average disability with time on "high dose" corticosteroid therapy, the maximum improvement occurring within the first three years. The degree of improvement in disability was considerably less in those inadequately treated, though the mortality rate was similar in the two groups. 66% of all survivors had essentially no functional disability at follow-up three or more years later, and in the majority of these cases the disease appeared to have burned itself out. 33% of cases had significant disability after three years, and in half of these the disease appeared to be still active.     

三例包涵体肌炎的临床与病理特点

目的探讨包涵体肌炎（ＩＢＭ）的临床与病理特点。方法总结３例ＩＢＭ病人的临床特点，并对肌活检标本进行酶组织化学、组织化学病理和超微病理研究。结果３例女性病人均在２４～３６岁发病，其临床特点为以双下肢无力起病，渐累及上肢，远端肢体受累常见。腱反射消失，血清肌酸激酶正常或轻度增高，肌活检光镜检查发现其主要病理改变为镶边空泡纤维，肌浆或肌核内有嗜酸性包涵体，肌内膜炎性细胞浸润和成群萎缩肌纤维。电镜观察发现３例均有肌浆内细丝或管状细丝包涵体，其中１例有核内包涵体。镶边空泡内含淀粉样细丝、髓样结构、絮状无结构物质和其他胞浆分解产物。肌核改变包括异染色质增多、核变大，核内包涵体及核崩解。结论电镜包埋、半薄切片定位是电镜下寻找包涵体并确诊ＩＢＭ的关键步骤。肌核改变可能是ＩＢＭ的病因基础，镶边空泡和肌浆内包涵体有可能来自于崩解的肌核。     

Early prednisone treatment in Duchenne muscular dystrophy

The purpose of this long-term, open parallel-group, double-consent study of alternate-day, low-dose prednisone in 2-4-year-old patients with Duchenne muscular dystrophy (DMD) was to determine whether prednisone produces a beneficial effect when given earlier than usual. Muscle function was evaluated by timed tests, and muscle strength with a hand-held myometer. After 55 months of treatment, the five patients (mean age 8.3 years) in the prednisone group were still able to get up from the floor, whereas two of the three in the control group had lost this ability. Side effects included a decline in growth rate in the prednisone-treated patients and excessive weight gain in one control and three treated patients. Because steroids are effective in prolonging function, but not in recovering lost function, we propose that treatment be started with low-dose prednisone in DMD patients as soon as the diagnosis is definite.     

Late onset Pompe disease: clinical and neurophysiological spectrum of 38 patients including long-term follow-up in 18 patients

To describe the clinical and neurophysiological spectrum and prognosis in a large cohort of biochemically and genetically proven late onset Pompe patients. Thirty-eight diagnosed with late onset Pompe disease at our neuromuscular department during 1985 and 2006 are described in detail. The mean delay from onset of symptoms or first medical consultation until diagnosis was 10.4 and 7.1 years, respectively. A different diagnosis was suggested in 11 of 38 patients. Ten patients underwent repeated muscle biopsies before diagnosis of Pompe disease was established. Limb girdle weakness was the most frequent presenting sign. Six patients complained of myalgia. Wolf-Parkinson-White syndrome was found in 3 of 38 patients. Respiratory failure preceded the onset of overt limb muscle weakness in three patients. The course of the patients was progressive in all, but there was a wide variety of progression, which did not correlate with the age of disease onset. In 71% of the patients, neurophysiological investigations revealed a myopathic EMG pattern, half of the patients had spontaneous activity including complex repetitive discharges. A normal EMG was found in 9% of the patients. Nerve conduction studies were normal in all. Pompe disease should be taken into consideration in patients with unexplained limb girdle muscular weakness with respiratory failure. Cardiac manifestations may not be restricted to infantile Pompe disease.     

电子转移黄素蛋白脱氢酶基因突变所致的核黄素反应性脂质沉积性肌病的临床、病理和基因特征分析

目的分析电子转移黄素蛋白脱氢酶(ETFDH)突变所致的核黄素反应性脂质沉积性肌病(RR-MADD)的临床特点、肌肉病理以及血、尿质谱筛查结果和基因突变特点,旨在为早期诊断和治疗提供帮助。方法回顾性分析该院2009年至2019年确诊的15例ETFDH突变所致的脂质沉积性肌病患者的各项资料。结果 15例患者平均发病年龄为(32.1±13.6)岁,均以肢体无力为首发症状,其中四肢起病者占53.3%,双下肢起病者占46.7%。所有患者的肌酶水平均升高;肌电图结果提示80%呈肌源性损害,13.3%为肌源性合并神经源性损害,6.7%结果正常。血、尿质谱的阳性检出率分别为66.7%和22.2%;基因检测提示所有患者存在ETFDH基因不同位点突变,其中单一杂合突变和复合杂合突变各占40%,纯合突变占20%。结论该病以波动性肌无力伴肌酶升高为主要表现,患者应尽快行肌肉病理检查,同时联合血、尿代谢筛查和基因检测有助于RR-MADD患者早期诊断和及时治疗。     

七叶皂苷钠、强的松治疗Bell麻痹的随机对照研究

目的　探讨七叶皂苷钠治疗Bell麻痹的有效性。方法　采用随机对照研究 ,收集首次诊断Bell麻痹的急性期患者 85例 ,随机分为七叶皂苷钠组 (七叶皂苷钠加基础治疗 ) 30例、强的松组 (强的松加基础治疗 ) 2 8例、基础治疗组 2 7例 ,基础治疗包括多种维生素、针灸、理疗等 ,均在发病 3天内给予相应的治疗。采用House Brach mann(H B)面神经麻痹评定标准 ,分别于治疗前与治疗后 1个月时评定面神经麻痹等级。结果　治疗前 3组患者性别、年龄、面瘫部位、发病至开始治疗时间、首次治疗时H B面瘫等级分布均无统计学差异 ,具有可比性。治疗后 1个月时三组患者H B面瘫等级经Kruskal Wallis秩和检验 ,有统计学差异 (P =0 0 4 8)。 3组间两两比较显示七叶皂苷钠组、强的松组面瘫恢复均优于基础治疗组 ,有统计学意义 (P值分别为 0 0 4 5、0 0 14 ) ;而七叶皂苷钠组与强的松组面瘫恢复比较无统计学差异 (P =0 6 16 )。结论　七叶皂苷钠可替代皮质类固醇治疗Bell麻痹 ,同时避免皮质类固醇的副作用。     

Dermatomyositis with inclusion body myositis pathology

The pathogenic role of inflammation in inclusion body myositis (IBM) remains uncertain. A 63‐year‐old man developed a severe, rapidly progressive myopathy with clinical features typical of dermatomyositis (DM), but muscle pathology was typical of IBM. Treatment with prednisone and methotrexate resulted in complete remission of symptoms. Together with two similar cases reported previously, this case suggests that the inflammatory process of DM may trigger the pathologic changes of IBM. Muscle Nerve, 2009     

Muscle fiber dysfunction contributes to weakness in inclusion body myositis

Atrophy and fatty infiltration are important causes of muscle weakness in inclusion body myositis (IBM). Muscle weakness can also be caused by reduced specific force; i.e. the amount of force generated per unit of residual muscle tissue. This study investigates in vivo specific force of the quadriceps and ex vivo specific force of single muscle fibers in patients with IBM. We included 8 participants with IBM and 12 healthy controls, who all underwent quantitative muscle testing, quantitative MRI of the quadriceps and paired muscle biopsies of the quadriceps and tibialis anterior. Single muscle fibers were isolated to measure muscle fiber specific force and contractile properties. Both in vivo quadriceps specific force and ex vivo muscle fiber specific force were reduced. Muscle fiber dysfunction was accompanied by reduced active stiffness, which reflects a decrease in the number of attached actin-myosin cross-bridges during activation. Myosin concentration was reduced in IBM fibers. Because reduced specific force contributes to muscle weakness in patients with IBM, therapeutic strategies that augment muscle fiber strength may provide benefit to patients with IBM.     

脂质沉积性肌病的临床、神经电生理和病理学特征

目的研究脂质沉积性肌病(LSM)的临床、神经电生理及病理学特点。方法回顾性分析5例LSM患者的临床、神经电生理及病理学资料。结果本组发病年龄平均为25.6岁;均为亚急性或慢性起病,病情缓慢进展或出现缓解复发;2例有家族史;主要表现为运动耐受差和不同程度的肌无力(5/5)、腱反射减弱或消失(5/5)、肌痛或肌压痛(4/5)、肌萎缩(3/5)、末梢型感觉障碍(2/5);肌酶轻至中度升高(4/5),肌电图表现周围神经源性损害合并肌源性损害(2/5),或者单纯肌源性损害(1/5);肌肉病理学显示纤维间、肌膜下、胞核周围大量排列成串的或成团的脂滴,无炎性细胞浸润。高肉碱、低脂肪饮食、以及糖皮质激素治疗有效。结论LSM临床以肌无力和运动不耐受为主要症状,神经电生理表现为肌源性损害和/或周围神经损害,肌肉活检为诊断脂质沉积性肌病所必需。     

Facioscapulohumeral dystrophy presenting as infantile facial diplegia and late-onset limb-girdle myopathy in members of the same family

We report a family with markedly variable myopathic weakness due to facioscapulohumeral muscular dystrophy (FSHD). The proband developed mild late-onset proximal limb weakness. Her two daughters had severe infantile facial diplegia, initially diagnosed as M?bius syndrome, and mild childhood-onset limb weakness and scapular winging. Results of facial muscle electromyography and muscle histopathology supported a myopathic disorder. This case study further highlights the broad clinical spectrum and intrafamily variability in FSHD, and the occasional absence of a positive correlation between fragment size and disease onset. Moreover, this study underscores the importance of considering FSHD in cases of infantile facial diplegia, especially in patients not demonstrating the full clinical features of M?bius syndrome. In difficult cases, facial muscle electromyography may help to differentiate myopathic from neuropathic weakness, and help guide further diagnostic studies.     

Reversible alexia, mitochondrial myopathy, and lactic acidemia

A 11-year-old boy of short stature had recurrent right temporal pounding headaches of 7 months' duration, and progressive visual loss for 3 days. There was a left hemianopia, alexia without agraphia, and diffuse muscle weakness. Investigation established the presence of a mitochondrial myopathy with pyruvate and lactic acidemia and increased serum content of sarcoplasmic enzymes. On treatment with prednisone, the patient's strength and reading skill improved, symptoms resolved, and muscle enzymes returned to normal. Three attempts to reduce steroids resulted in accentuation of symptoms, seizures, weakness, regression of reading skills, and elevation of serum enzymes. The alexia was also reversible.     

Glucocorticoid-sensitive hereditary inclusion body myositis

We report a hereditary muscle disorder with features of inclusion body myositis (IBM) in two adult sisters with slowly progressive asymmetrical muscle weakness. The findings of light microscopic and ultrastructural investigations of muscle biopsy specimens were consistent with a diagnosis of IBM. Both patients improved and stabilized on immunosuppressive treatment with corticosteroids and azathioprine. This differentiates our patients from other sporadic and familial cases of IBM. Clinical and histological features are described and compared with those of other previously reported families with IBM.     

Inflammatory myopathy with cytochrome oxidase negative muscle fibers: Methotrexate treatment

Inflammatory myopathy with cytochrome oxidase negative muscle fibers (IM/COX−) is characterized by slowly progressive weakness, most prominent in the quadriceps, muscle fibers with reduced COX staining and mitochondrial DNA mutations, and a poor response to corticosteroid treatment. We reviewed records of quantitative measurements of muscle strength in 7 IM/COX− patients to evaluate the outcomes after treatment with oral, once weekly, methotrexate for an average of 15 months. We compared the results to 6 patients with IM/COX− who received no long-term immunosuppression, and to 4 with inclusion body myositis (IBM) who received methotrexate during the same period. Methotrexate treatment of IM/COX− was followed by improved muscle strength in 5 of 7 patients, averaging 17 ± 5%. In contrast, there was no improvement in the strength of 6 untreated IM/COX− patients (−6 ± 4%; P = 0.003), or 4 methotrexate-treated IBM patients (1 ± 2%; P = 0.03). We conclude that, despite clinical similarities to inclusion body myositis, which is usually refractory to immunosuppressive therapy, strength in IM/COX− appears to improve with methotrexate treatment. Biopsy studies of inflammatory myopathies with evaluation of muscle for mitochondrial changes and vacuoles can help to direct the choice of appropriate immunomodulating treatments. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1724–1728, 1998     

脂质沉积性肌病

两例因四肢无力 ,生活不能自理入院 ,经实验室检查 ,肌活检发现肌原纤维间及肌膜下有成堆或成串的脂肪空泡 ,线粒体结构改变而诊为脂质沉积性肌病。经激素、核黄素及低脂饮食治疗后好转。再次肌活检发现一例脂质沉积已明显减轻 ,另一例病理改变完全消失。对患者进行为期近 10年的随访 ,患者情况一直稳定 ,无复发。两例为国内跟踪观察最长的病人 ,本病显示在确当的治疗下呈良性经过