假肥大型肌营养不良患儿的肌肉病理及dystrophin免疫组化SP法检测的临床意义

目的探讨肌肉病理及抗肌萎缩蛋白（dystrophin）免疫组化SP法检测在假肥大型肌营养不良诊断中的临床价值。方法通过组织学观察和免疫组化SP法检测方法,对50例假肥大型肌营养不良患儿[40例Duchenne型营养不良（DMD组）,10例Becker型营养不良（BMD组）]肌纤维膜dystrophin的表达、肌肉病理改变及临床表现进行观察,并与30例其他疾病（多发性肌炎3例、皮肌炎6例、糖元累积病1例、脂质累积病15例、周围神经病2例、脊肌萎缩症3例）对照组患儿进行对比分析。结果肌肉病理显示：DMD组中有30例肌肉病理改变较重,10例较轻;BMD组的肌肉病理改变较轻,这些均与年龄有关。免疫组化显示：DMD组肌肌纤维膜均有严重的dystro-phin缺失,BMD组肌纤维膜有50%~70%的dystrophin缺失;对照组无dystrophin缺失。结论肌肉病理及dys-trophin SP免疫组化检测对假肥大型肌营养不良具有较大的临床意义。     

Expression of transforming growth factor-beta 1 in dystrophic patient muscles correlates with fibrosis. Pathogenetic role of a fibrogenic cytokine.

Duchenne muscular dystrophy is a fatal disorder characterized by progressive muscular weakness, wasting, and severe muscle contractures in later disease stages. Muscle biopsy reveals conspicuous myofiber degeneration and fibrosis substituting muscle tissue. We quantitatively determined mRNA of the potent fibrogenic cytokine transforming growth factor-beta 1 by quantitative PCR in 15 Duchenne muscular dystrophy, 13 Becker muscular dystrophy, 11 spinal muscular atrophy patients, and 16 controls. Higher transforming growth factor-beta 1 expression was greater in Duchenne muscular dystrophy patients than controls (P = 0.012) and Becker patients (P = 0.03). Fibrosis was significantly more prominent in Duchenne muscular dystrophy than Becker muscular dystrophy, spinal muscular atrophy, and controls. The proportion of connective tissue in muscle biopsies increased progressively with age in Duchenne muscular dystrophy patients, while transforming growth factor-beta 1 levels peaked at 2 and 6 yr of age. Transforming growth factor-beta 1 protein was also detected by immunocytochemistry and immunoblotting. Our findings suggest that transforming growth factor-beta 1 stimulates fibrosis in Duchenne muscular dystrophy. Expression of transforming growth factor-beta 1 in the early stages of Duchenne muscular dystrophy may be critical in initiating muscle fibrosis and antifibrosis treatment could slow progression of the disease, increasing the utility of gene therapy.     

高频超声对Duchenne型肌营养不良症的诊断价值

目的　探讨Duchenne进行性肌营养不良症肌肉声像图的特点及其诊断价值。方法　应用高频超声检测 81例Duchenne进行性肌营养不良症患者下肢肌肉。按照年龄分为 4组 :3～ <7岁 13例 ,7～ <10岁 3 0例 ,10～ <13岁 3 0例 ,13～ 14岁 8例。选择 1～ 11岁健康儿童 2 0例作为对照组。依次对臀部、大腿部、小腿部肌肉行纵横切位超声扫查。结果　患者 3岁时 ,臀肌萎缩 ,皮下脂肪增厚 ;随着年龄的增长 ,臀肌、大腿部位肌肉、小腿肌肉和背肌萎缩呈现进行性加重 ,皮下脂肪增厚 ,各年龄组差异有显著性意义 (P <0 .0 1)。结论　高频超声可为Duchenne进行性肌营养不良症的诊断、病情随访和临床病理活检提供客观依据。     

Muscular dystrophy

The muscular dystrophies are a genetically heterogeneous group of progressive disorders that lead to the breakdown of the integrity of skeletal muscle. Numerous recent advances made in research into the molecular genetics of muscular dystrophy have highlighted the diversity of this family of disorders. Muscle biopsy allows the immunohistochemical analysis of various muscle specific proteins, and can provide important data enabling definitive diagnosis. Muscle biopsy is not always necessary, such as in the case of Duchenne or Fukuyama type dystrophies, which are relatively easy to diagnose by genetic testing; in such cases, however, consideration must given to the ethical implications of testing. The future promises the development of new therapeutic approaches and clinical applications based on genetic diagnostic data.     

Sickness impact in people with muscular dystrophy: a longitudinal study over 10 years

OBJECTIVE: To describe changes of function in terms of sickness impact over 10 years in adult patients with different types of muscular dystrophy. DESIGN: Patients with muscular dystrophy answered the Sickness Impact Profile and Self-report ADL questionnaires in 1991 and 2001. SETTING: The study population was identified in a comprehensive prevalence study in the county of Orebro, Sweden. SUBJECTS: The study group comprised 44 people grouped according to whether they had myotonic dystrophy or muscular dystrophy with proximal or distal muscles affected. MAIN MEASURES: Comparison was made between assessments of sickness impact in terms of function at the two time points. RESULTS: Most obvious deterioration over time was in activities of daily living that require finger and arm strength. Ambulation was significantly decreased in myotonic dystrophy and proximal muscular dystrophy. Those walking without assistive devices decreased from 91% to 52%, and the number with a disability pension increased from 36 to 55%. There was a relatively small influence with regard to psychosocial dysfunction assessed by the Sickness Impact Profile. CONCLUSIONS: This longitudinal study shows the deteriorating functions reported by patients with muscular dystrophy. This knowledge could be used to formulate new interventions in order to offer appropriate support and treatment to this patient group.     

Comparison study of chest physiotherapy home training programmes on respiratory functions in patients with muscular dystrophy

OBJECTIVE: To compare the effects of home training programmes, threshold inspiratory muscle training and breathing exercise on spirometry and maximal pressures in patients with muscular dystrophy. DESIGN: Prospective blinded 12-week study. SETTINGS: Cardiopulmonary department of university hospital. SUBJECTS: Twenty-three patients with muscular dystrophy (17 patients with limb girdle muscular dystrophy and 6 patients with Becker muscular dystrophy) assigned to the threshold inspiratory muscle training and breathing exercise groups with alternate allocation. METHODS: Spirometry, maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax) were measured before and after training. In the threshold inspiratory muscle training group threshold pressure load was determined as equal to 30% of weekly PImax measurement. In the breathing exercise group, patients performed deep and forceful diaphragmatic and segmental exercises. All patients performed exercises at home and once a week at hospital under supervision. RESULTS: The improvement of PImax in the threshold inspiratory muscle training group was more significant than the improvement observed in the breathing exercise group (P=0.05). PEmax increased significantly only in the breathing exercise group (P=0.01). Spirometry results did not change significantly in both groups after the training. CONCLUSIONS: We conclude that respiratory muscle strength is enhanced by training in the patients with muscular dystrophy who are ambulatory, but inspiratory and/or expiratory training effect is specific to the trained muscles. The techniques that improve the strength of respiratory muscles should be included in the physiotherapy management of patients with muscular dystrophy.     

High-frequency ultrasonography of skeletal muscle in children with neuromuscular disease.

Ultrasonography of the thigh and calf was performed in 24 children who had primary neuromuscular disease and in 20 healthy children. The ultrasound image was clearly abnormal in all patients with progressive muscular dystrophy, and in the majority of children with benign myopathic disorders; the principal changes were increased muscular echogenicity and increased attenuation of ultrasound with a reduced bone surface echo. In 13 patients, the ultrasound findings were correlated with pathologic changes seen in muscle biopsy specimens: a clear correlation (r = .85) was found. Muscular dystrophies had a higher score of abnormal ultrasonographic and microscopic findings, while the more benign muscular diseases had a lower score.     

Quantifying Lower Limb Muscle Stiffness as Ambulation Function Declines in Duchenne Muscular Dystrophy with Acoustic Radiation Force Impulse Shear Wave Elastography

Duchenne muscular dystrophy (DMD) is a progressive muscular disease, but validated imaging tools to quantify muscle microstructure alteration as mobility declines are lacking. We aimed to determine the feasibility of using acoustic radiation force impulse shear-wave elastography (ARFI/SWE) in the quantitative assessment of lower limb muscle stiffness in DMD patients. Shear wave velocities (SWVs) of lower limbs were measured in 39 DMD patients and 36 healthy controls aged 3–20 y. Mean SWV values of the controls and of the DMD patients at different ambulatory stages were compared using analysis of variance with Bonferroni correction. The DMD group had increased lower limb muscle stiffness compared with controls. Stiffness of the tibialis anterior and medial gastrocnemius muscle decreased from ambulatory to early non-ambulatory stages, whereas stiffness of the rectus femoris muscle increased from ambulatory to late non-ambulatory stages. We describe how SWV changes in lower limb muscles have the potential to predict ambulatory decline in DMD.     

成人型脊髓性肌萎缩症的骨骼肌病理与肌萎缩的关系

背景:脊髓性肌萎缩症是运动神经元疾病中病变仅影响下运动神经元的一组疾病。成人型少见,目前对其研究较少。目的:总结成人型脊髓性肌萎缩症骨骼肌病理学特征。设计:以诊断为依据的回顾性研究。地点和对象:收集1998-02/2002-02在解放军第八一医院南京医学院第二附属医院和南京军区总医院经肌肉活检确诊的、有完整临床资料的门诊和住院患者共46例。方法:结合临床特征及病理学改变进行分析。主要观察指标:病史、家族史、完整体格检查、相关血液及血生化、肌电图和肌肉活检。结果:临床表现为进行性对称性肢体近端肌萎缩,肌无力,实验室检查血肌酸磷酸肌酶12例中轻度升高,肌电图检查2例正常,3例呈轻度肌源性损害,余37例呈神经元性损害,肌活检主要为小群性肌萎缩,腺苷三磷酸酶染色见同型肌群化及肌纤维代偿性肥大。结论:肌活检对成人型脊髓性肌萎缩症具有诊断和鉴别诊断意义。适当、持久的康复锻炼可能对维持患者的运动功能有帮助。     

Stem cell therapy for muscular dystrophy

Muscular dystrophy is a heterogeneous group of neuromuscular disorders that manifests as progressive muscle weakness, muscle wasting and, in many cases, death. Although there has been enormous progress in the molecular understanding of muscular dystrophy, there is still no cure. There are, however, several different therapeutic options under investigation, including adult-derived stem cell transplantation. Encouraging and pioneering experiments in mouse models for Duchenne's muscular dystrophy (DMD) demonstrated that myoblasts could be transplanted into dystrophic muscle; these myoblasts repaired a small proportion of damaged myofibres. Subsequent work has been devoted to optimisation of this technique. In doing so, a number of adult-derived stem cells have been isolated, characterised and used in promising animal transplantation experiments. Further research is ongoing, and is clearly necessary to make this therapy a viable treatment option for patients with muscular dystrophy.     

一种罕见的运动神经元病亚型：散发性面肩肱型脊肌萎缩症一例并文献复习

目的 探讨面肩肱型脊肌萎缩症的临床表现和早期诊断.方法 对我院2006年收治的1例患者临床资料结合文献进行回顾性分析.结果 该患者为青年女性,隐袭起病,进行性进展.初期表现为选择性累及颜面、肩胛带肌群和上肢近端肌群,早期血浆肌肉酶谱正常,电生理检查和肌肉活检均提示神经源性损害.结论 面肩肱型脊肌萎缩症与肌营养不良性面肩肱型肌萎缩临床上极为类似,应早期进行电生理和肌肉活检检查协助确诊.     

肌酸磷酸激酶增高的脊髓性肌萎缩症10例临床与肌电图分析

目的总结血清肌酸磷酸激酶 (creatine kinase,CK)增高的脊髓性肌萎缩( spinal muscular atrophy, SMA)临床与肌电图的关系及临床意义. 方法收集 10例 CK增高的 SMA病例,进行临床及肌电图分析,其中 6例作了肌肉活检. 结果CK增高可见于脊髓性肌萎缩各型,升高的程度各有不同.肌电图检查除 2例为混和性损害外,余均为神经源性损害.肌肉病理检查除 1例为肌性改变外,余均为神经源性肌萎缩. 结论CK增高不能作为 SMA与进行性肌营养不良的鉴别诊断指标,必须结合肌电图与肌肉活检.在诊断 SMA时,当肌活检为肌性损害,反复多次的肌电图的结果更可靠;当肌电图结果不明确时,肌活检结果为确定诊断的最可靠依据.     

Sit-to-stand and Walking Ability in Patients with Neuromuscular Conditions

Summary

This study of 64 subjects with neuromuscular conditions (51 myotonic dystrophy (MD), six fascioscapulohumeral muscular dystrophy (FMD) and seven Charcot-Marie-Tooth (CMT) disease) investigated the relationship between combined weakness in quadriceps and tibialis anterior muscles in each of the three disability groups, ability to move from sitting to standing, and walking ability. The association between sit to stand and walking class was determined for each disability group.Sit-to-stand was classified as 0 = unable, 1 = needs aid of upper limbs and 2 = able to do unaided. Walking ability was classified as 0 = unable to walk, 1 = uses aid to walk and 2 = walks unaided. Muscle strength was graded 0 to 5 by manual muscle testing with a combined maximum possible score of 20 for the four muscles tested.A significant difference (p < 0.0003) was seen in the combined muscle strength between the FSH group compared to the MD and CMT groups. Muscle weakness had a significant effect on sit-to-stand and walking ability in all subjects (p < 0.0001 and p < 0.0001 respectively). A Fisher’s exact test demonstrated a highly significant association between sit-to-stand and walking category in the MD group only.     

Assessment of quadriceps femoris muscle atrophy and hypertrophy in neuromuscular disease in children

Midthigh muscle and subcutaneous tissue thickness were measured using a real-time linear array ultrasound scanner in 50 patients attending our Muscle Clinic; 28 had muscular dystrophy and 21 spinal muscular atrophy. In muscular dystrophy the muscle thickness was found to be normal or increased, whereas in spinal muscular atrophy it was reduced, with an associated increase in subcutaneous tissue thickness that did not relate to obesity. Measurement of muscle and subcutaneous tissue thickness provides a more accurate way of assessing muscle atrophy and hypertrophy than clinical assessment, and is a useful guide in the discrimination between muscular dystrophy and spinal muscular atrophy.     

Social identity and the International Classification of Handicaps: An evaluation of the consequences of facioscapulohumeral muscular dystrophy

The objective of this study was to evaluate the consequences of facioscapulohumeral muscular dystrophy (FSH MD) using two different but complementary procedures: an analysis based on the three different dimensions of disablement developed by the WHO — impairment, disability, and handicap — and a study of the psychological repercussions on social identity.

Sixty-eight individuals with FSH MD, with 68 members of a control group, responded to a battery of psychosocial questions. Individuals with muscular dystrophy were also studied with reference to the dimensions of impairment, disability and handicap. The results showed that there are close correlations among measures of the three dimensions of disablement. Evaluations made by people with muscular dystrophy of the seriousness of their own disablement are strongly linked to objective measures of impairment. Furthermore, we found that having muscular dystrophy does have certain consequences for an individual's self-identity, although the degree to which one's self-image is validated is to some extent independent of the seriousness of the illness.     

High creatine kinase levels and white matter changes: Clinical and genetic spectrum of congenital muscular dystrophies with laminin alpha-2 deficiency

Primary deficiency of laminin alpha-2 due to mutations in the LAMA2 gene accounts for 30% of all patients with congenital muscular dystrophy. Here, we present seven patients with partial or total laminin alpha-2 deficiency (MDC1A) with a wide clinical spectrum, ranging from ambulant patients to patients who were never able to stand or sit. We identified two pathogenic mutations in the LAMA2 gene in all patients except for one patient in whom only one mutation was found. Six of the mutations were previously undescribed. In some of the milder cases, laminin alpha-2 expression in the muscle biopsy was only slightly reduced. These findings emphasize that analysis of the LAMA2 gene might be necessary in patients with muscle weakness, cerebral white matter changes and high creatine kinase levels, even in the presence of laminin alpha-2 in the muscle biopsy.     

Social identity and the International Classification of Handicaps: an evaluation of the consequences of facioscapulohumeral muscular dystrophy.

The objective of this study was to evaluate the consequences of facioscapulohumeral muscular dystrophy (FSH MD) using two different but complementary procedures: an analysis based on the three different dimensions of disablement developed by the WHO--impairment, disability, and handicap--and a study of the psychological repercussions on social identity. Sixty-eight individuals with FSH MD, with 68 members of a control group, responded to a battery of psychosocial questions. Individuals with muscular dystrophy were also studied with reference to the dimensions of impairment, disability and handicap. The results showed that there are close correlations among measures of the three dimensions of disablement. Evaluations made by people with muscular dystrophy of the seriousness of their own disablement are strongly linked to objective measures of impairment. Furthermore, we found that having muscular dystrophy does have certain consequences for an individual's self-identity, although the degree to which one's self-image is validated is to some extent independent of the seriousness of the illness.     

血清VEGF的表达与肌营养不良症的关系

目的检测肌营养不良症患者的血清血管生长因子（VEGF）水平,鉴定其是否与肌营养不良症的疾病发展有关。方法对46例肌营养不良患者,其中32例Duchenne肌营养不良症（DMD）、9例Becker肌营养不良症（BMD）、5例强直性肌营养不良症（DM）患者的血清VEGF水平进行检测。15例健康人和8例疾病患者为对照组。结果DMD患者血清VEGF为（274．7±2．52）pg／ml,BMD患者的为（358．8±9．64）pg／ml,DM患者为（165．0±6．34）pg／ml,而健康对照组为（148．3±2．91）pg/ml,疾病对照组为（153．7±5．42）pg／ml。与DM组和对照组相比,BMD的VEGF水平显著提高。而DMD组中卧床的患者相对于坐轮椅的DMD、DM组和对照组则VEGF水平显著升高。结论VEGF可以反映肌肉组织低氧和／或缺血状况,并且与DMD和BMD患者的疾病发展过程有关。     

Isoforms of creatine kinase: MM in the study of skeletal muscle damage

Isoforms of creatine kinase (CK) MM have been analysed in plasma from normal subjects and patients with muscular dystrophy using isoelectric focusing techniques. Most plasma samples analysed contained three isoforms of CK-MM of isoelectric points 7.26 (MMI), 6.85 (MMII) and 6.45 (MMIII) although in some plasma samples two additional isoforms of isoelectric points 7.12 and 6.65 were seen. Patients with muscular dystrophy were found to have a generally higher proportion of CK-MMI in their plasma than normal subjects and this was relatively unaffected by large variations in the total creatine kinase activity. By comparison eccentric exercise in normal subjects was found to result in a large increase in total plasma CK activity which then declined to normal over a period of approximately 6 days. CK-MMI was found to increase initially followed by CK-MMII and CK-MMIII. Analysis of the isoforms in biopsy samples of human muscle revealed the presence of two of the bands found in plasma (CK-MMI and MMII) and a third muscle specific isoform, while incubation of muscle homogenates in plasma induced the formation of CK-MMIII and the two isoforms of pI 7.12 and 6.65. It is concluded that analyses of CK-MM isoforms in human plasma can provide useful information on the extent and relative time course following an episode of muscle damage but that in patients with muscular dystrophy the large variations in plasma CK activity are not reflected in the proportion of CK found in each isoform.(ABSTRACT TRUNCATED AT 250 WORDS)