Multiple sclerosis and mitochondrial myopathy: An unusual combination of diseases

A woman with definite multiple sclerosis (MS) and mitochondrial myopathy is described. There were widespread white matter lesions on magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) abnormalities and evoked response changes. Muscle biopsy showed ragged red fibres (RRFs) and cytochrome c oxidase (CoX) deficiency. Southern blot analysis revealed a large deletion of mitochondrial DNA (mtDNA). The patient may be affected by two unrelated diseases, MS and mitochondrial myopathy, but this combination has never previously been reported.     

An unusual myopathy: speckled muscle fibers due to enlarged mitochondria

We report a 52-year-old woman who presented with a 6-month history of proximal muscle weakness, elevated serum creatine kinase, and myopathic pattern on electromyography (EMG). Histology of the muscle shows a speckled pattern due to clustering of enlarged mitochondria. The pathology resembles that of selenium deficiency. The patient was found to have borderline low serum selenium and also low vitamin D and thyroid-stimulating hormone. The cause of this unusual myopathy is probably multifactorial. This case is important because the unusual pathological picture represents a potentially treatable myopathy. In addition, we hope that publication of the complex clinical and biochemical abnormalities of this case, in conjunction with other case reports, may facilitate future elucidation of muscle mitochondrial function and dysfunction.     

Emery-dreifuss humeroperoneal muscular dystorphy: An X-linked myopathy with unusual contractures and bradycardia

Clinical, electromyographic, and muscle biopsy findings in the two largest known families with emery-Dreifuss humieroperoneal muscular dystorphy indicate that this is an X-linked recessive muscle disease with stereotyped clinical manifestations but with variable pathological and electromyographic characteristics. Elbow contractures, involvement of humeral muscles, Hyporeflexia, and abnorman electorcardiograms are present in our patients. The disorder is associated with a potentially lethal cardiac arrhythmia that should be managed by pacemaker insertion. The skeletal muscle disease is slowly progressive and is usually not life threatening. Muscle biopsy commonly shows type I fiver atrophy. Electromyogrphy usually indicates myopathy, though the classic findings of myopathy may not be present in every muscle.     

Polyglucosan body disease myopathy: an unusual presentation

Polyglucosan body disease (PBD) is a slowly progressive adult-onset glycogen storage disorder that typically affects upper and lower neurons. Myopathy, as a complication of PBD has been reported rarely and clinically manifests as chronic limb-girdle muscle weakness. We report an unusual case of PBD myopathy presenting as an asymmetric motor syndrome that clinically overlapped with amyotrophic lateral sclerosis, further expanding the phenotype of this disorder.     

Centronuclear myopathy with unusual mitochondrial abnormalities

The case of a 34-years-old man is described with a progressive myopathy characterized by limb weakness and atrophy, involvement of facial, masticatory and extraocular muscles. The prominent features of the muscle biopsy were the presence of centrally located nuclei in most fibers. There was also an atrophy and predominance of type I fibers. Both clinical and morphological features were consistent with the diagnosis of centronuclear myopathy. Electron microscopic studies showed the presence of mitochondria with paracrystalline inclusions near the centralized nuclei but not in the subsarcolemmal position. This hitherto unreported feature led the authors to re-evaluate the hypothesis on the pathogenesis and the nosological classification of this myopathy.     

Centronuclear myopathy with unusual clinical picture

The authors describe two cases of familial muscle disease, a mother and her daughter, characterized by centrally placed nuclei and a predominance of hypotrophic type 1 fibers. Clinically the patients exhibited a muscular weakness and atrophy localized mainly distally. Both showed hypertrophy of their calves. The nosological classification of the cases is uncertain; however, both are considered as examples of centronuclear myopathy with unusual clinical features.     

代谢性肌病的循证治疗

目的评价代谢性肌病之临床治疗方案及可能出现的药物不良反应,为其循证治疗制定最佳方案。方法以代谢性肌病（metabolic myopathy）、线粒体肌病（mitochondrial mypathv）、脂质沉积性肌病（lipid storage myopathy）、糖原贮积病（glycogen storage dieases）、内分泌性肌病（endocrine myopathy）、药物毒性肌病（drug toxicity myopathy）、治疗（treatment）等中英文词汇为检索词,检索美国国立医学图书馆（PubMed）、英国Cochrane图书馆、ClinicalKey数据库、国家科技图书文献中心等数据库中有关代谢性肌病（包括线粒体肌病、脂质沉积性肌病、糖原贮积病、内分泌性肌病、药物毒性肌病）治疗相关临床指南、系统评价、随机对照试验、临床对照试验、回顾性病例分析和病例观察研究,采用Jadad量表进行文献质量评价。结果经筛选共纳入28篇文献（临床指南6篇、系统评价5篇、随机对照试验10篇、临床对照试验7篇）,其中23篇为高质量文献（≥4分）、5篇为低质量文献（〈4分）。对其治疗原则、不同方法获得的疗效及安全性评价显示：（1）糖原贮积病主要采用α-葡糖苷酶替代治疗,同时进食高蛋白饮食,运动前服用少量果糖,逐渐减少患者体力活动。（2）脂质沉积性肌病可补充肉碱,运动前或运动时补充碳水化合物,日常低脂饮食。（3）线粒体肌病可予辅酶Q10、B族维生素、维生素K、维生素C等,适当的有氧运动结合力量训练可以更安全、有效地提高患者的运动耐受性。（4）内分泌性肌病需首先治疗原发病。（5）药物毒性肌病需停用致病药物。结论代谢性肌病多为遗传性疾病,其治疗的根本出路是基因治疗;内分泌性肌病和药物毒性肌病需治疗原发病或停用致病药物。鉴于此,需借助循证医学方法为代谢性肌病提供最佳临床证据。     

An oxidative defect in metabolic myopathies: Diagnosis by noninvasive tissue oximetry

Metabolic myopathies due to a variety of enzymatic deficiencies are well recognized. The dynamics of oxygen delivery and utilization during exercise have not been observed previously in these disorders. We used a noninvasive optical technique to measure oxygen consumption in the exercising limb in normal subjects and patients with metabolic myopathies. We measured near-infrared spectra of hemoglobin in the gastrocnemius muscle during treadmill exercise in 10 normal subjects, 1 patient with cytochrome c oxidase deficiency, 2 patients with myophosphorylase deficiency, 3 patients with phosphofructokinase deficiency, and 2 patients with carnitine palmityl transferase deficiency. All normal subjects demonstrated a sustained deoxygenation during exercise, indicating an efficient utilization of delivered oxygen. The patient with cytochrome c oxidase deficiency demonstrated consistent oxygenation during exercise, indicating an underutilization of delivered oxygen. In the patients with myophosphorylase or phosphofructokinase deficiency, abnormal oxgenation during exercise indicated an oxidative defect due to a lack of pyruvate production. In the patients with myophosphorylase deficiency, changes in oxidation coincident with glucose utilization and “the second wind phenomenon” were observed. Patients with carnitine palmityl transferase deficiency demonstrated a normal deoxygenation during exercise. Noninvasive tissue oximetry during exercise demonstrates specific abnormalities in a variety of metabolic myopathies, indicating abnormal oxygen utilization, and will be a useful addition to the clinical investigation of exercise intolerance.     

Myophosphorylase deficiency: the course of an unusual congenital myopathy

A 59-year-old man had proximal weakness and wasting that started in early childhood. EMG was "myopathic," serum CK activity was increased, and muscle biopsy showed accumulations of glycogen. Biochemical studies revealed elevated glycogen concentration and absence of myophosphorylase activity. This unusual presentation of a long-standing, painless, and quite static weakness due to myophosphorylase deficiency represents another example of clinical heterogeneity.     

Oculopharyngeal myopathy with inflammation and calcinosis: an unusual phenotype

The case is reported of a patient with progressive proximal and distal weakness, dysphagia, respiratory weakness, calcifications, ptosis and ophthalmoparesis with inflammation, rimmed vacuoles and positive amyloid and ubiquitin on muscle biopsy. The histopathological features fit best with inclusion body myositis, but ophthalmoparesis and ptosis have not previously been described. The clinical phenotype fits best with hereditary inclusion body myopathy or distal-oculopharyngeal muscular dystrophy, but the degree of inflammation seen is unusual. None of these are associated with calcinosis.     

代谢性肌病研究发展史

本文依据年代和科研进展两个层面对代谢性肌病的发展过程进行了回顾。展望其研究的努力方向仍是寻找不同代谢性肌病之特异性生物学标志物,并针对这些特异性标志物开发与研制特异性诊断与治疗措施。