Muscle pathology in Marinesco-Sj?gren syndrome

Three of 4 adult patients with Marinesco-Sj?gren syndrome (MSS; 2 males and 2 females, aged 26-31 years) in 2 families became non-ambulant because of slowly progressive muscular weakness rather than cerebellar ataxia. Other clinical features in these 4 patients were typical for MSS: bilateral cataracts from infancy, mental retardation, severe cerebellar atrophy, multiple skeletal abnormalities and hypergonadotropic hypogonadism. EMG demonstrated a myopathic pattern and serum CK was mildly elevated. Muscle biopsies from these 3 patients showed myopathic changes including a marked variation in fiber size, an increased number of fibers with centralized nuclei, and scattered necrotic and regenerating fibers. Fiber type analysis with myosin ATPase staining showed type 1 fiber predominance, type 2B fiber deficiency and mild increase in type 2C fibers. Muscle biopsy changes and the clinical course indicate that our MSS patients suffered from a chronic dystrophic process similar to that in congenital muscular dystrophy.     

Myopathy in Marinesco-Sjögren syndrome: an ultrastructural study

Summary Seven muscle biopsies from patients with the clinical characteristics of Marinesco-Sjögren syndrome (MSS) revealed myopathic changes of two types; muscle fiber necrosis followed by regeneration and focal myofibrillar degeneration inducing autophagocytosis with rimmed vacuole formation. In two young patients, massive muscle fiber necrosis with phagocytic invasion was the predominant feature and autophagic phenomenon was minimal, resembling the findings in progressive muscular dystrophy. Myofibrillar degeneration with autophagic phenomenon was prominent in five adult patients. The coexistence of these two degenerative processes and the secondarily induced reactive changes of muscle fiber hypertrophy, interstitial fibrosis, occasional ragged-red fibers and type 1 fiber predominance, are responsible for the wide spectrum of muscle pathology in MSS. The dense double-membrane structure surrounding myonuclei, previously reported as being specific to MSS, was present in only one biopsy.     

Neuropathy with lysosomal changes in Marinesco-Sj?gren syndrome: fine structural findings in skeletal muscle and conjunctiva.

The light- and electron-microscopical findings in the skeletal muscle and conjunctiva of 6 patients with Marinesco-Sj?gren syndrome (MSS) were presented. All patients were related and showed the cardinal clinical symptoms of the syndrome: congenital cataracts, mental retardation, delayed statomotor development, and cerebellar ataxia. The most prominent alteration found in the skeletal muscle of four patients was extensive neurogenic atrophy with conspicuous groups of atrophic muscle fibers. Additional findings were vacuolar degeneration and secondary, unspecific changes like slight mitochondrial alterations and increased variability in muscle fiber calibers. The ultrastructural examination revealed double-membrane structures near to, but not in direct contact with the nucleus. The nuclear changes described earlier (7, 20) were not found in any of the cases. Conjunctival biopsies revealed a marked increase in the number of lysosomes in fibroblasts. In summary, to the well known myopathic damage of muscles in MSS a neurogenic component should be added. Disturbed lysosomal function is to be considered as the basic abnormality, though the enzyme defect has not yet been identified. In cases of clinically suspected MSS, examination of a conjunctival biopsy is highly recommended.     

Turns-amplitude analysis and motor unit potential analysis in myasthenia gravis

OBJECTIVES: The aims of this study were to investigate myopathic changes in myasthenia gravis (MG) by using turns-amplitude analysis (TAA) and quantitative motor unit potential duration analysis (MUPan), to correlate myopathic changes with severity and duration of the disease and the results of diagnostic tests including repetitive nerve stimulation test (RNS), single fiber electromyography (SFEMG), and anti-acetylcholine receptor antibody (AChR-ab), and to compare the sensitivities of these two methods in detecting myopathic changes in MG. MATERIALS AND METHODS: We studied both MUPan and TAA in 32 patients with MG. RESULTS: The MUPan study showed myopathic changes in 12 patients (37.5%); TAA revealed a myopathic pattern in 4 (12.5%) and a neurogenic pattern in 4 cases (12.5%). Two of the 4 patients with a myopathic change by TAA also had short-duration mean MUP on the MUPan. No statistically significant association was found between the myopathic changes either by MUPan or TAA, and the various clinical and laboratory features. CONCLUSION: We conclude that MUPan is a more sensitive method than TAA in showing myopathic changes in MG, and that TAA is of limited help in demonstrating them.     

Myopathy in Marinesco-Sjögren syndrome: an electrophysiological study

ABSTRACT Electrophysiological studies were performed in 7 patients with Marinesco-Sjögren syndrome in order to search for neuromuscular involvement in this multiorgan disorder. In 6 patients muscle biopsies were also obtained. Light microscopic examinations of the biopsies showed extensive myopathic changes, and in two patients ragged red fibers were found. Electron microscopy showed subsarcolemmal accumulation of abnormal mitochondria in all. Concentric needle EMG revealed unequivocal myopathic changes, more extensive in the anterior tibial than in the biceps brachii muscle. Motor and sensory conduction velocities in the peripheral nerves were normal. There were remarkably high amplitudes of sensory responses. Macro EMG studies in the biceps brachii muscle in four patients showed increased amplitude and area of the macro MUPs. This may be due to abnormal membrane function. Both electrophysiological and morphological findings confirm myopathic features of Marinesco-Sjögren syndrome.     

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.     

"Myopathic" changes in chorea-acanthocytosis. Clinical and histopathological studies

Four cases of chorea-acanthocytosis were studied with special reference to muscular changes. All the cases showed the clinical stigmata of oro-linguo-facial dyskinesia with tongue biting, mild neurogenic muscular involvement and acanthocytosis. Serum creatine kinase (CK) was persistently elevated, showing MM type isozyme predominance. Histopathological studies of the peroneus brevis muscle showed prominent small group atrophy, increase of small fibers on diameter analysis, frequent angulated fibers, and angulated fibers with increased acid phosphatase activity. These findings are compatible with chronic denervation. However, central nucleation (approximately 10%) and fiber splitting (2-8%) were also found in all cases. These are compatible with myopathic changes. No correlation of these "myopathic" changes and serum CK levels was found. The "myopathic" findings are probably secondary to chronic denervation.     

EMG and nerve conduction studies in children with congenital muscular dystrophy

Motor and sensory nerve conduction velocities (NCVs) and needle electromyography (EMG) results were reviewed in 26 children with different types of congenital muscular dystrophy (CMD), including patients with mutations in the genes LAMA2, FKRP, and COL6A2. In every patient, at least one EMG examination detected myopathic changes that were predominant in proximal muscles, although EMG performed at birth was normal in two patients. Brief bursts of high-frequency repetitive discharges were electrically elicited in four patients. Uniformly slowed motor NCVs without signs of denervation were observed in seven patients: five merosin-deficient, one merosin-positive, and one with unavailable merosin status. The merosin-deficient neuropathy also involved sensory nerves in three patients and worsened with age in two. In conclusion, myopathic EMG changes were typical and early findings in all types of CMD. An associated neuropathy was detected in most patients with merosin-deficient CMD, and also in a child with normal merosin expression.     

Myopathic changes in patients with long-term fatigue after COVID-19

ObjectiveTo investigate the peripheral nerve and muscle function electrophysiologically in patients with persistent neuromuscular symptoms following Coronavirus disease 2019 (COVID-19).MethodsTwenty consecutive patients from a Long-term COVID-19 Clinic referred to electrophysiological examination with the suspicion of mono- or polyneuropathy were included. Examinations were performed from 77 to 255 (median: 216) days after acute COVID-19. None of the patients had received treatment at the intensive care unit. Of these, 10 patients were not even hospitalized. Conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG) findings from three muscles were compared with 20 age- and sex-matched healthy controls.ResultsqEMG showed myopathic changes in one or more muscles in 11 patients (55%). Motor unit potential duration was shorter in patients compared to healthy controls in biceps brachii (10.02 ± 0.28 vs 11.75 ± 0.21), vastus medialis (10.86 ± 0.37 vs 12.52 ± 0.19) and anterior tibial (11.76 ± 0.31 vs 13.26 ± 0.21) muscles. All patients with myopathic qEMG reported about physical fatigue and 8 patients about myalgia while 3 patients without myopathic changes complained about physical fatigue.ConclusionsLong-term COVID-19 does not cause large fibre neuropathy, but myopathic changes are seen.SignificanceMyopathy may be an important cause of physical fatigue in long-term COVID-19 even in non-hospitalized patients.     

Benign muscular dystrophy with autosomal dominant inheritance.

A slowly progressive myopathy was discovered in a family in four successive generations. Eight patients (four female, four male) from three generations were examined and they showed muscle weakness affecting predominantly proximal, but also distal, muscles. Two patients had unequivocal findings in childhood, the others showed myopathy in their twenties or thirties. Working ability was lost in physically demanding jobs in the thirties, but activities of daily living were still preserved. Elbow contractures, tight heel cords and contractures of the interphalangeal joints were frequent. Serum CK activity was usually mildly elevated and electromyographic examinations revealed myopathic changes. Histopathological changes were compatible with moderately advanced muscular dystrophy in two patients, the six others had mild myopathic changes.     

Late-onset mitochondrial myopathy with dystrophic changes due to a G7497A mutation in the mitochondrial tRNASer (UCN) gene

Mutations of mitochondrial tRNA genes are usually associated with multi-systemic disorders with onset of symptoms in childhood or early adulthood. Dystrophic myopathic changes are not typical features of these disorders. We report two siblings with a severe progressive myopathy of late onset without external ophthalmoplegia and without involvement of the central and peripheral nervous system. Muscle biopsy specimens showed severe myopathic changes similar to those found in muscular dystrophies. Molecular analysis revealed a G7497A mutation in the mitochondrial tRNA^Ser(UCN) gene. In both patients, the proportion of mutated mitochondrial DNA in muscle was more than 97%. Mitochondrial disorder associated with the G7497A mutation has to be included into the differential diagnosis of severe progressive late-onset myopathy with histopathological dystrophic myopathic changes. Mitochondrial myopathy and high level of mutated mtDNA might be a characteristic of the G7497A tRNA^Ser(UCN) mutation.     

Calendar of events

We compared serum creatine kinase (CK) levels between spinobulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) and reviewed available histochemical studies of frozen sections of muscle biopsies. CK levels and the frequency of patients with elevated CK levels were significantly higher in the SBMA group when compared with the ALS group. CK levels occasionally approached values up to 8 times the upper limit of normal in the SBMA group. In addition to the chronic neurogenic changes in the muscle biopsy, all SBMA patients showed one or more myopathic changes. Increased numbers of markedly hypertrophic fibers were consistently seen in all patients. It is not clear whether the elevated CK level is directly related to the increased number of hypertrophic fibers or to other myopathic features. Based on these findings, we recommend genetic testing for SBMA in cases of male patients with motor neuron disease who present with a significantly elevated serum creatine kinase level, even when other characteristic clinical features of SBMA are absent. Muscle Nerve 40: 126–129, 2009     

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.     

Myopathic changes detected by quantitative electromyography in patients with MuSK and AChR positive myasthenia gravis

Myopathic changes are frequent a electrophysiological finding in patients with muscle specific tyrosine kinase (MuSK) positive myasthenia gravis (MG). The aim of this study was to explore the importance of quantitative electromyography (EMG) in the detection of myopathic changes in MuSK MG patients. Classical and quantitative EMG were performed in 31 MuSK and 28 acetylcholine receptor (AChR) positive MG patients, matched by sex, age, disease duration and severity. Classical EMG revealed the presence of myopathic changes more frequently in MuSK MG compared to AChR MG patients, especially in the facial muscles. Quantitative EMG registered myopathic lesions more frequently than classical EMG, but the frequency was similar between MuSK and AChR MG patients. Quantitative EMG revealed myopathic changes in the majority of both MuSK and AChR positive MG patients. This examination is sensitive, but it cannot be used to differentiate between MG patients belonging to the different disease groups. It should not be used in isolation. Rather, it should complement classical EMG in the detection of myopathic changes.     

Diagnostic accuracy of clinical data, quantitative electromyography and histochemistry in neuromuscular disease. A study of 105 cases

One hundred and five (105) cases of muscle weakness were reviewed in order to evaluate the reliability of clinical diagnosis, quantitative EMG, and muscle histochemistry in neuromuscular disorders. Patients were grouped into 3 categories: group I, disorders which could be diagnosed by clinical observation alone (38 patients); group II, disorders in which the EMG and biopsy were necessary for delineation (63 patients); disorders in which it was not possible to make a diagnosis because the clinical and laboratory studies were contradictory (4 patients). In group I, only one patient showed an inconsistency between clinical and laboratory data. In group II, the EMG and biopsy were concordant in all but 4 cases of Kugelberg-Welander syndrome with neuropathic EMG and myopathic biopsy. In group III, 4 patients had a myopathic EMG and neuropathic biopsy.The overall concordance of EMG and histochemistry was greater than 90%. The laboratory studies also discerned 2 different categories of disease, “neuropathic” and “myopathic”. The consistency in EMG and histochemistry correlation suggests that a true division between neuropathic and myopathic disorders exists.     

The rigid spine syndrome and Emery-Dreifuss muscular dystrophy

We present five patients, three of whom suffered from a rigid spine syndrome and two from Emery-Dreifuss muscular dystrophy.

One patient with rigid spine syndrome showed a nonprogressive course, normal cardiac rhythm and mild myopathic changes in muscle histology, while in the other two patients there was a rapidly progressive course, sinus tachycardia without cardiac conduction defects and marked fiber necrosis in muscle histology.

The two patients suffering from Emergy-Dreifuss muscular dystrophy showed a very mildly progressing course, myopathic changes in muscle histology, cardiac conduction defects and deviations in electrocardiograms. These findings show that rigid spine syndrome can be distinguished from Emery-Dreifuss muscular dystrophy.     

Clinical forms of inclusion body myositis: 12 cases

Inclusion body myositis is now a well-known disease but its incidence is underestimated. We report 12 cases with clinical heterogeneity. Three groups of patients could be described. The first one corresponded to asymmetrical muscle involvement and distribution with a slow clinical course (4 cases). The second was characterized by a polymyositis-like syndrome (3 cas), but steroid therapy was ineffective. The last group mimicked a chronic spinal muscular atrophy (4 cases). One patient showed a scapuloperoneal syndrome. Both myopathic and neurogenic EMG patterns were present in 6 patients; a neurogenic pattern was found in 4 cases and a myopathic pattern in 2 cases. In all patients, muscle biopsies showed rimmed vacuoles with eosinophilic inclusions. In 9 cases ultrastructural studies displayed abnormal filaments of 15-18 nm in diameter in the vacuoles. Intranuclear filaments were rarely observed. The significance of the filaments is unknown and their specificity is doubtful because they are present in other myopathies with rimmed vacuoles (some distal myopathies and oculopharyngeal muscular dystrophies). Finally a rich inflammatory exudate was present in 8 patients only.     

血管炎：不宁腿的一个常见原因

目的 探讨不宁腿的常见原因及其与血管炎的关系。方法 观察37例临床表现为不宁腿而暂未发现其它原发病患者的实验室检查、肌电图及腓肠肌活检情况。结果 检查发现37例患者中2例糖尿病;1例贫血;1例类风湿性关节炎;25例患者腓肠肌活检发现存在血管炎性改变,其中7例EMG报告有肌源性损害,其它实验室检查均未发现异常。结论 血管炎是不宁腿的一个较常见原因。     

Neurophysiological changes in neurologically asymptomatic hypothyroid patients: a prospective cohort study.

This is a prospective cohort study on neurologically asymptomatic patients with primary hypothyroidism. It was conducted to evaluate the frequency and pattern of neurophysiological changes in this group of patients. Twenty-three subjects were included over a period of 2(1/2) years. Neurophysiological evaluation included nerve conduction studies (NCS) of median, ulnar, and peroneal motor nerves as well as median palmar and ulnar and sural sensory responses. Electromyography of deltoid, first dorsal interosseous, vastus lateralis, and tibialis anterior muscles was performed with concentric needle electrodes in which duration, amplitude, and stability of motor unit action potentials, recruitment, and interference pattern were evaluated. NCS showed that 52% of the patients had some abnormality, predominantly of the motor demyelinating pattern, as evidenced by prolonged F-wave and distal latencies with normal amplitudes in most affected nerves. Thirty percent of patients had median mononeuropathy consistent with carpal tunnel syndrome. Nondisfigurative myopathic changes in the form of myopathic motor unit action potentials without spontaneous activity were seen in 74% of the patients, most commonly in deltoid (70%). Frequencies of involvement of other muscles were 39% in the vastus lateralis muscle, 26% in tibialis anterior muscle, and 9% in the first dorsal interosseous muscle. We conclude that electromyographic/NCS changes commonly exist in treated, neurologically asymptomatic patients with hypothyroidism and are most frequently myopathic. Median neuropathy is the most common nerve abnormality. Other nerves are involved, with a higher tendency for motor nerve demyelination. We speculate that some neuromuscular changes secondary to hypothyroidism persist after treatment and that motor nerve abnormalities are less likely to be symptomatic than sensory nerve changes in these patients.     

Reappraisal of alcoholic myopathy: Clinical and biopsy study on chronic alcoholics without muscle weakness or wasting

To determine if alcoholic neuropathy which causes denervation of the distal muscles of chronic alcoholics also produces a subclinical myopathy of their proximal muscles, we studied 11 chronic alcoholics who had no muscular weakness or wasting. Six patients demonstrated distal hyporeflexic (ankle jerks) sensory neuropathy on clinical examination. Four patients, one of whom was asymptomatic, had slow peroneal motor nerve conduction velocities. Patterns of neuropathy were present in the electromyograms of the proximal muscles of two patients. Muscle biopsy studies with enzyme histochemistry indicated denervation atrophy and myopathic changes in the contralateral quadriceps muscles of eight patients. As denervation atrophy was present, we concluded that these myopathic changes represented the effects of denervation of these muscles. We conclude, therefore, that the proximal subclinical alcoholic myopathy, previously described as primary by ourselves and others, is the result of denervation due to the well-known alcoholic neuropathy.