A case of asymmetrical arthrogryposis--a clinical study and a preliminary report on the value of CT-scanning

Following the introduction of the conception that arthrogryposis is a symptom and not a clinical entity, a case of the very rare asymmetric form of neurogenic arthrogryposis is presented. The asymmetry of congenital contractures and weakness is associated with hemihypotrophy. The value of muscular CT-scanning prior to muscle biopsy is demonstrated. Muscular CT-scanning shows the extension of adipose tissue, which has replaced damaged muscles and thereby indicates the exact site for muscle biopsy. Since orthopaedic treatment in arthrogryposis can be unrewarding due to severe muscular degeneration, preoperative scanning may provide additional important information on muscular function and thus be of benefit for surgery. The advantage of muscular CT-scanning in other forms of arthrogryposis requires further determination. The differential diagnosis with Werdnig-Hoffmann disease is discussed.     

Limb girdle syndromes. Clinical, morphological and electrophysiological studies

The clinical syndrome of slowly progressive proximal limb and limb girdle muscular weakness and atrophy, or limb girdle syndromes (LGS), has a diverse aetiology. Several of the congenital, mitochondrial and other metabolic myopathies and spinal muscular atrophies are recently recognized causes of LGS. Thus the position of limb girdle muscular dystrophy (LGMD) as a discrete entity in the nosology of muscle disease deserves reappraisal. We have therefore reevaluated our experience of 33 patients in this light. Detailed clinical, electrophysiological, and pathological studies including autopsies in 2 cases, were performed. As a result we are confident that LGMD does exist as a sporadic or autosomal dominant (2 families) or recessive condition (2 families). There are therefore probably at least 2 distinct genotypes. Typical LGMD (18 patients in our series) is characterized by slowly progressive symmetrical proximal upper and lower limb girdle weakness and atrophy, elevation of the serum creatine kinase at some stage, dystrophic or less severe myopathic muscle lesions on biopsy, and myopathic EMG findings. Two minor subgroups of LGMD were identified in our series with similar clinical and laboratory features but distinguishable by the development of either facial (4 patients) or by distal limb muscle involvement (3 patients). A further group of patients with sporadic LGS (5 patients) had slowly progressive proximal symmetrical upper and lower limb-girdle weakness and atrophy with myopathic or neurogenic features on either EMG or muscle biopsy so that the precise characterization was difficult. Two of these patients had distal limb muscle involvement and contractures. One patient had upper limb-girdle muscle atrophy with normal lower limbs. A disorder affecting muscle, nerve or both remains a possibility in these cases.     

肯尼迪病的临床特征与基因突变四例

目的探讨肯尼迪病(KD)的临床特征与基因突变。方法分析4例经基因确诊的KD患者的临床资料。结果 4例患者均为男性,发病年龄分别为35、47、48、36岁,例2有家族史,例4既往双手静止性震颤10余年,4例均以肢体无力起病并以肢体无力为主要症状,例2、例3、例4伴有舌肌萎缩及纤颤,例4伴明显的面部及腹部肌肉跳动。例1初诊未确诊,例2误诊为肌炎,例3误诊为运动神经元病。4例血清肌酸激酶均升高;肌电图(EMG)4例均呈广泛慢性神经源性损害;例1、例2、例3肌肉病理示神经源性损害伴肌源性损害;4例患者雄激素受体基因外显子中CAG重复序列次数均40(分别为53、51、49、52)。结论 KD的临床特点为缓慢进展的延髓和四肢近端肌肉萎缩无力,可伴有内分泌或代谢异常;肌肉病理以神经源性损害为主,多伴肌源性损害。KD临床表现常不典型,需与多种疾病鉴别,基因检测可确诊。     

X-linked recessive bulbospinal neuronopathy: a report of ten cases

A form of adult onset 'bulbospinal muscular atrophy' of X-linked recessive inheritance is described in 10 patients from eight families. Muscle weakness in the limbs was mainly proximal and developed in the third to fifth decades of life, often preceded by muscle cramps on exertion and tremor of the hands. Weakness and fasciculation of the facial muscles and tongue were prominent. All the patients had gynaecomastia and some were infertile. Two had diabetes mellitus. Motor nerve conduction studies were normal but most patients had small or unrecordable sensory action potentials in the absence of clinical sensory loss. Plasma creatine kinase levels were considerably elevated and muscle biopsies showed neurogenic atrophy together with secondary myopathic changes. The importance of recognising this distinctive disorder in single cases (six of the present series) is emphasised.     

Facioscapulohumeral muscular dystrophy presenting isolated monomelic lower limb atrophy. Report of two patients with and without 4q35 rearrangement

Facioscapulohumeral muscular dystrophy has a distinctive regional distribution but variable clinical expression and may be markedly asymmetrical. We report two patients presenting weakness and wasting confined to a single lower limb. Creatine kinase was slightly increased, electromyogram and muscle biopsy were myopathic. Muscle computed tomography showed normal shoulder, mid-arm, pelvic and mid-thigh scans but involvement of calf muscles. In both cases, weakness of facial and periscapular muscles was found in other family members unaware of the disease. Molecular analysis showed 4q35 deletion in one family. These cases broaden the presentation of facioscapulohumeral muscular dystrophy to include isolated monomelic atrophy of lower limb with calf muscle involvement.     

The diagnostic power of motor unit potential analysis: an objective bayesian approach.

The notion of a "myopathic" or "neuropathic" electromyogram (EMG) is usually based on qualitative visual and acoustical impressions. Conventional quantification defines abnormality but not diagnosis, which requires interpretation of patterns of change. Discriminant analysis is a model for this multivariate decision. It tells how probable it is that a motor unit potential (MUP) comes from a normal, myopathic, or neuropathic muscle. Accumulation of single MUP information by a sequential Bayesian algorithm produced diagnostic probabilities above 0.95 in 91% of all muscles (223 biceps brachii muscles from 80 patients with motoneuron disorders, 56 patients with neuropathies, 71 patients with myopathies, and 34 controls). Two muscles from patients with neurogenic disorders were misclassified as "myopathic." Misclassification was more frequent only in myositis (4 of 28 muscles) and in oculopharyngeal muscular dystrophy (2 of 4 muscles). MUP discriminant classification was as sensitive as, and more specific than, conventional quantitative EMG, which discriminated between myopathic and neuropathic in only 22% of the muscles. This rate was 59% for discriminant analysis. As a knowledge-based expert system, MUP discriminant analysis successfully distinguishes between myopathic, neuropathic, and unclassifiable MUP samples. It discloses more information than conventional quantitative MUP analysis.     

Chronic neurogenic quadriceps amyotrophy

Two patients with chronic neurogenic quadriceps amyotrophy are reported. A 61-year-old woman had symmetrical wasting and weakness of the quadriceps femoris of eight years' duration. A biopsy revealed neuropathic changes, and electromyograms showed neurogenic as well as myopathic patterns in the quadriceps and other muscles. A 29-year-old woman had long-standing wasting limited to the quadriceps and hip muscles. EMG and biopsy were compatible with neurogenic atrophy. She had a brother suffering from a more widespread and severe form of the disease. These cases suggest that chronic neurogenic quadriceps amyotrophy is a forme fruste of Kugelberg-Welander disease.     

Muscle “islands”: An MRI signature distinguishing neurogenic from myopathic causes of early onset distal weakness

Muscle MRI has an increasing role in diagnosis of inherited neuromuscular diseases, but no features are known which reliably differentiate myopathic and neurogenic conditions. Using patients presenting with early onset distal weakness, we aimed to identify an MRI signature to distinguish myopathic and neurogenic conditions. We identified lower limb MRI scans from patients with either genetically (n = 24) or clinically (n = 13) confirmed diagnoses of childhood onset distal myopathy or distal spinal muscular atrophy. An initial exploratory phase reviewed 11 scans from genetically confirmed patients identifying a single potential discriminatory marker concerning the pattern of fat replacement within muscle, coined “islands”. This pattern comprised small areas of muscle tissue with normal signal intensity completely surrounded by areas with similar intensity to subcutaneous fat. In the subsequent validation phase, islands correctly classified scans from all 12 remaining genetically confirmed patients, and 12/13 clinically classified patients. In the genetically confirmed patients MRI classification of neurogenic/myopathic aetiology had 100% accuracy (24/24) compared with 65% accuracy (15/23) for EMG, and 79% accuracy (15/19) for muscle biopsy. Future studies are needed in other clinical contexts, however the presence of islands appears to highly suggestive of a neurogenic aetiology in patients presenting with early onset distal motor weakness.     

Myofibrillar myopathies

Myofibrillar myopathies represent a group of muscular dystrophies with a similar morphologic phenotype. They are characterized by a distinct pathologic pattern of myofibrillar dissolution associated with disintegration of the Z-disk, accumulation of myofibrillar degradation products, and ectopic expression of multiple proteins and sometimes congophilic material. The clinical features of myofibrillar myopathies are more variable. These include progressive muscle weakness, that often involves or begins in distal muscles but limb-girdle or scapuloperoneal distributions can also occur. Cardiomyopathy and peripheral neuropathy are frequent associated features. EMG of the affected muscles reveals myopathic motor unit potentials and abnormal irritability often with myotonic discharges. Rarely, neurogenic motor unit potentials or slow nerve conductions are present. The generic diagnosis of myofibrillar myopathies is based on muscle biopsy findings in frozen sections. To date, all myofibrillar myopathy mutations have been traced to Z-disk-associated proteins, namely, desmin, αB-crystallin, myotilin, ZASP, filamin C and Bag3. However, in the majority of the myofibrillar myopathy patients the disease gene awaits discovery.     

Diagnostic value of electromyography and muscle biopsy in arthrogryposis multiplex congenita

Arthrogryposis multiplex congenita (AMC), a clinical syndrome characterized by multiple congenital joint contractures, frequently is caused by lesions in the peripheral nervous system. Two standard tests for the evaluation of the motor unit are nerve conduction studies/electromyography (NCS/EMG) and muscle biopsy. We reviewed the diagnostic value of these two studies in the evaluation of AMC over a 23-year period, analyzing 38 patients with AMC who had NCS/EMG, muscle biopsy, or both. Final diagnoses were classified as neurogenic (8 patients), myopathic (10 patients), "other" (12 patients), or unknown (8 patients). Neither test alone had consistently high sensitivities, positive predictive values, or specificities. However, when NCS/EMG and muscle biopsy were concordant for neurogenic or myopathic findings, they were more accurate than either test alone, especially for neurogenic diseases. Test results were most commonly discordant in patients with "other" or unknown diagnoses. These findings suggest that when the clinical evaluation indicates a specific syndromic, developmental, or exogenous cause, NCS/EMG and muscle biopsy are not helpful and may not need to be performed. When the history, examination, and genetic evaluation are unrevealing, NCS/EMG and muscle biopsy together provide valuable diagnostic information.     

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.     

Welander''s distal myopathy: clinical, neurophysiological and muscle biopsy observations in young and middle aged adults with early symptoms.

Nine young or middle aged patients with early symptoms of Welander's distal myopathy were subjected to a detailed neurological examination including quantitative sensory testing, determination of motor and sensory nerve conduction velocity (NCV), sensory nerve action potentials, electromyography (EMG) and muscle biopsy from the tibialis anterior muscle (TA). Slight weakness of the extensors of the fingers and hands was found in all nine patients, and of the dorsiflexors of the feet in seven. All patients had a distal sensory disturbance most prominent for temperature which agrees with earlier observations. EMG changes in TA and extensor digitorum communis (EDC) muscles were of myopathic type. Slight abnormalities compatible with either myopathy or early neuropathy were found in one muscle biopsy. These findings indicate that a neurogenic lesion affecting at least the peripheral sensory system is present at an early stage of Welander's distal myopathy and that the neurogenic lesion might precede the myopathic changes.     

Ocular myasthenia: evaluation of Tensilon tonography and electronystagmography as diagnostic tests

The value of electronystagmography (ENG) and of tonography in monitoring the beneficial effect of edrophonium chloride (Tensilon) on the extraocular muscles in myasthenia gravis has been assessed. Studies were performed on 17 patients with myasthenia gravis and on 18 control subjects, of whom nine had extraocular muscle weakness due to myopathic or neurogenic lesions.     

Comparison of the muscle fiber diameter and satellite cell frequency in human muscle biopsies.

Satellite cells are responsible for the formation of postnatal muscle fibers. The number, mitotic activity, and differentiation potential of satellite cells and the muscle fiber diameter are tightly regulated events in normal muscle. The signal that induces satellite cells to stop proliferation once the determined muscle fiber size has been reached in normal growth is not known. The aim of the present study was to determine whether a correlation exists between satellite cell frequency and muscle fiber diameter in human muscle disease. Muscle biopsies from 7 cases of Duchenne muscular dystrophy (DMD), 8 other muscular dystrophies, 23 cases of inflammatory myopathy, and 22 cases of neurogenic atrophy were examined. The satellite cell number was elevated in DMD and neurogenic atrophy but not in other muscular dystrophies or inflammatory myopathies. Nevertheless, in all the diseased muscles, but not in normal controls, there was a significantly higher relative frequency of satellite cells with increasing fiber diameter. It has been shown before that satellite cells show ultrastructural and autoradiographic signs of activation and proliferation in myopathic and neurogenic conditions. We assume that we are dealing with activated, not quiescent, satellite cells in diseased muscle and that under these conditions the fiber diameter does not represent a stop signal for satellite cells to proliferate. The data suggest that not only the number of satellite cells matters in diseased muscle, as has been shown before, but that it is their behavior that influences, at least in part, progress and severity of muscle diseases.     

Longitudinal fibre splitting in neurogenic muscular disorders--its relation to the pathogenesis of "myopathic" change.

In 15 patients with neurogenic muscular disorders, including cases of motor neuron disease, Wohlfart-Kugelberg-Welander disease, Davidenkow's scapuloperoneal syndrome, peripheral neuropathy and traumatic neuropathies, muscle biopsies were carried out, usually after EMG or single fibre EMG investigation. Enzyme histochemical and electronmicroscopic techniques were used to study longitudinal fibre splitting and its quantitative relation to the general changes in the biopsies. In 9 cases serial sections were used to study the longitudinal extent and character of fibre splitting. Longitudinal fibre splitting was found in 14 cases. It was prominent in Type 1 fibres, and in those biopsies in which hypertrophy was most marked. It was often associated with central migration of sarcolemmal nuclei. Ultrastructurally there was evidence that splitting consisted of mechanical disruption of the myofibrillar pattern, followed by an active process of membrane formation. We suggest that longitudinal splitting of muscle fibres, induced by overload of poorly innervated, hypertrophied fibres, can account for many of the "myopathic" changes found in neurogenic muscular disorders.     

Myopathy in thiamine deficiency: analysis of a case

BACKGROUND: Tenderness in the limb muscles has been reported anecdotally in patients with beriberi neuropathy, but clinical effects of thiamine deficiency on skeletal muscle have received little attention. OBJECTIVE: To describe a patient with thiamine deficiency who manifested myopathic symptoms and responded well to thiamine supplementation. PATIENT: A 26-year-old woman with neuropathy and heart failure associated with thiamine deficiency also complained of myalgia and weakness, most troublesome in the proximal portions of the limbs. RESULTS: Serum creatine kinase, myoglobin, and aldolase concentrations were abnormally elevated. Magnetic resonance imaging of lower limb muscles demonstrated areas of high signal intensity in T2-weighted images and showed Gd-DTPA enhancement. A biopsy specimen from the quadriceps muscle showed myopathic changes without neurogenic changes. Abnormalities improved well with thiamine administration. CONCLUSION: Myopathy may occur in patients with thiamine deficiency.     

Myopathy in the adult form of glycogenosis II. Two case reports and review of the literature

Clinical, neurophysiological, morphological and biochemical investigations were performed in 2 patients with the adult form of glycogenosis II and related to the findings of 58 well-documented cases published in the literature. According to these findings three types can be distinguished from each other. The first one is characterized by an involvement of the limb-girdle muscles only. The second type shows the same pattern with additional progressive insufficiency of the respiratory muscles. The third type presents with weakness of the respiratory muscles without any other severe muscle involvement. Our case 1 can be related to the first, our case 2 to the second type. EMG-studies in case 1 showed myopathic changes and myotonic discharges without clinical signs of myotonia. A myotonic pattern was described in one third of the published cases. In case 2 neurogenic changes as well as in 4 cases in the literature were found. The muscle biopsy is the diagnostic clue in the differential diagnosis of progressive myopathy in the adult. Patients with glycogenosis II show glycogen storage specially in type I-fibres. The enzyme defect can be confirmed biochemically in muscle tissue or cultured fibroblasts. Various therapeutic concepts have been tried in patients with glycogenosis II but most of them remain disappointing. A diet with a low carbohydrate and a high protein proportion was observed to be of some benefit. In patients with respiratory muscle involvement artificial ventilation support showed a positive effect on the general condition for some time.     

Myopathy in Childhood Muscle-Specific Kinase Myasthenia Gravis

BackgroundAdult and pediatric patients suffering from MuSK (muscle-specific kinase) -antibody positive myasthenia gravis exhibit similar features to individuals with acetylcholine receptor (AChR) antibodies, but they differ in several characteristics such as a predominant bulbar, respiratory and neck weakness, a generally worse disease severity and a tendency to develop muscle atrophy. Muscle atrophy is a rare phenomenon that is usually restricted to the facial muscles.ResultsWe describe a girl with MuSK-antibody positive myasthenia gravis who developed a myopathy with severe generalized muscular weakness, muscle atrophy, and myopathic changes on electromyography.ConclusionThis is the first published example of a generalized myopathic syndrome in myasthenia gravis. We review the relevant literature and discuss the hypothesis of a mitochondrial myopathy as a pathogenic mechanism in MuSK-antibody positive myasthenia gravis.     

头颅下垂综合征和轴性肌病

头颅下垂综合征指患者站立时颈脊部伸肌群无力抬头,因而头颅下垂,背部弯曲。平卧时可缓解。该综合征由原发性和继发性的病因造成。原发性的轴性肌病,病因不明,十分罕见。这种肌病发生于40￣60岁,主要累及颈脊旁肌群,出现头颅下垂。脊旁肌肌电图和组织活检证实为一种慢性肌病。本病是一种应引人注意的临床肌病症状群之一。     

Emery-Dreifuss muscular dystrophy: anatomical-clinical correlation (case report)

We report on a man that had weakness of humeroperoneal distribution associated with limited range of motion of the cervical spine and elbows since he was 5 years old. At age 26 he developed tachycardia episodes. A complex arrhythmia was discovered, and a nodal ablation was done with a cardiac pacemaker implanted. The patient had an arrhythmia and sudden death followed this. Emery-Dreifuss muscular dystrophy is a rare recessive X-linked muscular disorder where mixed patterns in electromyography and muscle histology (neurogenic and/or myopathic) have caused nosological confusion. The autopsy findings are here described and correlated to the clinical features in an attempt to better understand the ambiguous findings concerning the process etiology.