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。     

Colchicine-induced myopathy with myotonia in a patient with chronic renal failure

Although colchicine induced myopathy has been described in patients with chronic renal failure, colchicine induced myopathy with myotonia has been reported very rarely. A 49-year-old man with chronic renal failure was hospitalised for investigation of fatigue, malaise and severe pain in all extremities. He was on colchicine therapy for 5 months. Neurological examination showed mildly decreased sensation in a distal symmetric pattern in lower extremities, moderate proximal limb weakness, hyporeflexia and severe myalgia on palpation. No clinical evidence of myotonia was present. Laboratory studies showed elevated creatine phosphokinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Electromyographic (EMG) findings were compatible with myopathy and abundant, widespread myotonic discharges were determined. Muscle biopsy was consistent with vacuolar myopathy. After withdrawal of colchicine, CK, LDH, AST and ALT levels were normalised and the symptoms were disappeared gradually. In conclusion, the detection of myopathic motor unit potentials with myotonic discharges on EMG in patients on colchicine therapy is an important finding and it is possible to suggest that this clue may lead to the invasive procedure of muscle biopsy unnecessary.     

肌原纤维肌病的临床与病理学特征(附1例报告)

目的研究肌原纤维肌病的临床与病理学特征。方法回顾性分析1例肌原纤维肌病患者的临床和病理学资料。结果本例患者中年起病,表现为进行性四肢近端肌无力,有轻度肌萎缩。肌电图示:双下肢神经源性损害。病理检查示:大量肌纤维内含有胞浆体,偶见镶边空泡,含有胞浆体的肌纤维内,出现肌原纤维网结构紊乱及结蛋白异常沉积。结论肌原纤维肌病在临床表现上缺乏特异性,肌纤维内肌原纤维网结构紊乱,出现大量胞浆体及结蛋白异常沉积是其特征性病理改变。     

肯尼迪病的临床分析和分子遗传学诊断

目的 分析3例肯尼迪病的临床表现、电生理及遗传学特征。方法 收集2018年11月-2019年7月本院收治的3例肯尼迪病患者的临床资料包括病史、体格检查、实验室检查、电生理等,检测患者及家族成员雄性激素受体(Androgen Receptor)基因的CAG重复数。结果 3例患者均中年男性,表现为四肢近端和延髓肌无力、肌束震颤萎缩、乳腺发育,缓慢发病,进行性加重。EMG均显示广泛神经源性损害, 感觉神经传导存在异常。基因检测CAG重复数分别为43、51和51。结论 肯尼迪病的临床特点为成年男性,肢体缓慢进行性无力,伴多肌肉萎缩、震颤,同时合并雄激素不敏感综合征, EMG呈运动神经源性损害的表现,CAG重复数显著增多。     

A case of mitochondrial myopathy with mononeuritis multiplex

A case of mitochondrial myopathy with mononeuritis multiplex was described. A 55-year-old man was hospitalized because of blepharoptosis and muscle weakness. His mother also showed blepharoptosis in her elderly stage of life. He had been healthy until 46 years of age, when he first noticed difficulty of speech, followed by bilateral blepharoptosis, weakness of upper limbs, and sensory disturbance in the left occipital, and left upper and lower extremities. These symptoms progressed slowly. On admission, bilateral blepharoptosis was recognized. Slightly to moderate muscle wasting and weakness were observed in the face, neck, trunk, and extremities. Areflexia was observed in the upper extremities. Paresthesia was observed in the left occipital and left hip, and superficial sensation was impaired in the left upper and lower extremities. Electromyographic examination of extremities showed neurogenic changes in the distal muscles and myogenic changes in the proximal muscles. Motor conduction velocities were normal, but sensory conduction velocities decreased in amplitude on the left upper extremity and were not evoked on the left lower extremity. Muscle biopsy specimen revealed numerous "ragged-red" fibers. Cytochrome c oxidase stain showed a decrease in intensity of staining. A sural nerve biopsy showed slight axonal degeneration and slight loss of nerve fibers. Biochemical analysis on biopsy muscle showed partial deficiency of cytochrome c oxidase activity.     

A manifesting carrier of Duchenne muscular dystrophy presenting mosaic distribution of dystrophin negative and positive muscle fibers

A 25-year-old female patient with an approximate 10-year-history of slowly progressive muscle weakness was diagnosed as a manifesting carrier of Duchenne muscular dystrophy (DMD) because her muscle biopsy showed scattered fibers with no dystrophin on immunohistochemical staining. She had no family history of neuromuscular disorders. She was in good health until about 14 years of age, when she developed muscle weakness and atrophy of the extremities with slow aggravation. On admission at the age of 25 years, she had asymmetrical muscle atrophy in the lower extremities; the left femur, right femur, left crus, and right crus measured 36.0, 40.5, 31.5, and 35.5 cm in circumference, respectively. However, the muscle weakness of the extremities was symmetrical with no laterality, and the proximal muscles in the lower extremities were predominantly affected to 3+/5 MMT test. She walked with a mild wadding manner and stood up with Gower' maneuver. Deep tendon reflexes of the extremities were almost normoactive with no pathologic reflexes. As to laboratory findings, serum enzymes of muscular origin were elevated; GOT was 44 IU/l, GPT 60 IU/l, LDH 829 IU/l, CK 4238 IU/l, and aldolase 31 SL units. The electromyogram showed myopathic changes mixed with some neurogenic components. Peripheral nerve conduction velocity was normal. A computed tomography of the skeletal muscles showed more marked atrophy and lower density in the left lower extremity than in the right. The biopsied left gastrocnemius muscle demonstrated a marked variation in fiber size with some necrotic and regenerating fibers. On immunohistochemical stain with anti-dystrophin antibody, the dystrophin negative fibers were scattered among positive fibers in a mosaic distribution.     

Nonaka肌病伴面部肌肉受累

目的 报道1个伴随面部肌肉受累及的Nonaka型远端性肌肉病家系的临床和病理特点，讨论其发病机制。方法 先证者在中年早期起病。主要临床表现为胫前肌为主的四肢远端肌无力和肌萎缩，伴随有面肌和胸锁乳突肌力弱以及眼睑下垂，股四头肌不受累。肌酶轻度升高。肌电图提示肌源性损害。对患者进行胫前肌活检，进行组织学，酶组织化学和超微结构检查。家族中其妹妹也具有相同的临床表现。出现下肢远端为主的肌无力和肌萎缩。结果 肌肉病理改变特点是出现肌纤维肥大和萎缩。伴随核内移和肌纤维分裂现象。在部分肌纤维内可见镶边空泡和胞浆体。电镜下可见肌纤维内和核内的管丝包涵体以及髓样小体，其中出现在膜下的管丝包涵体具有细胞核的轮廓，可以看到细胞核变性后形成致密破碎结构。结论 结合患者的家庭史，临床表现和病理学改变特点。此患者可以考虑为Nonaka肌病，我们证实此病可以伴随面部肌肉的受累及。其发病机制可能与肌核的变性有关。     

Clinicopathological phenotype of ALS with a novel G72C SOD1 gene mutation mimicking a myopathy

A 71-year-old woman with a family history of amyotrophic lateral sclerosis (ALS) was investigated for symmetrical, proximal limb and abdominal muscle weakness. Initial examination showed mild proximal muscle weakness in the arms and legs, slightly elevated serum creatine kinase (CK) level, and normal electromyographic (EMG) findings. A myopathy was the presumed diagnosis. Over the next year, weakness became severe and tendon reflexes became unelicitable; no upper motor signs were present. EMG then showed acute and chronic denervation and a muscle biopsy showed target fibers and grouped atrophy. DNA analysis revealed a G72C CuZn-superoxide dismutase (SOD1) mutation. Fasciculations were absent throughout the disease. The patient died 53 months after symptom onset and autopsy revealed loss of lower motor neurons (LMN) and SOD1-positive inclusions. This case expands the phenotypic spectrum of ALS associated with SOD1 mutations to include presenting features that mimic a myopathy.     

Case of 12-year-old boy with idiopathic recurrent neuralgic amyotrophy

Here we report a 12-year-old boy with idiopathic neuralgic amyotrophy who had two episodes of shoulder pain followed by shoulder muscle atrophy and weakness at the age of 7 and 11 years, respectively. These symptoms were self-limited and disappeared within 9 months. During the second episode, electromyograph (EMG) revealed neurogenic changes in the deltoid muscle. Muscle imaging showed the right deltoid muscle atrophy with slightly high intensity areas on T1 and T2 weighted images in MRI. Muscle biopsy from the right deltoid muscle revealed neurogenic changes with denervating and reinnervating processes. Neuralgic amyotrophy is characterized by neuralgic pain followed by weakness and atrophy at a unilateral extremity and is usually self-limited. EMG and imaging studies showed focal neurogenic abnormalities, which were confirmed by muscle biopsy. Neuralgic amyotrophy usually occurs in young adults and it is very rare in children.     

Myoadenylate deaminase deficiency with progressive muscle weakness and atrophy caused by new missense mutations in AMPD1 gene: case report in a Japanese patient

A 46-year-old woman with exertional myalgia developed slowly progressive weakness in her lower extremities. She had slight muscle weakness in her facial and upper extremities, and severe muscle weakness and atrophy in lower extremities more marked in the proximal portions. Serum creatine kinase was slightly elevated. After ischemic forearm exercise test, blood ammonia had no elevation although lactate level increased normally. The computed tomography revealed that a characteristic distribution of skeletal muscle involvement with proximal and flexor muscles more severely affected than distal and extensor in the lower extremities. In addition, the left sternocleidomastoid muscle showed marked atrophy with an asymptomatic weakness of over 20 years duration suggesting abnormal development. Needle EMG examination showed a large number of easily recruited, short-duration, low-amplitude motor unit potentials in all extremities. Muscle biopsy showed absence of adenosine monophosphate deaminase activity with normal cytochrome c oxidase and phosphorylase activity. With the muscle enzyme activity assay, adenosine monophosphate deaminase activity was found to be lower than 0.2% of the controls. The DNA analysis revealed that she was compound heterozygote involving two missense mutations (R388W and R425H) in exon 9 and exon 10 of AMPD1 gene. This is the first report of primary myoadenylate deaminase deficiency with progressive weakness and atrophy caused by novel compound heterozygous mutations of AMPD1 gene, and suggests that adenosine monophosphate deaminase is closely related not only to energy metabolism but also to the development of skeletal muscle.     

13例神经肌炎的临床及肌电图研究

目的:探讨神经肌炎的临床特点以及肌电图(EMG)、神经传导速度(NCV)的诊断价值。方法:分析13例神经肌炎临床表现、EMG、NCV结果。结果:13例患者均以肌肉受累为主要临床表现;11例并发有神经病变的症状及体征。13例患者NCV均有异常。所检测的104根神经NCV异常率为57.7%。F波异常率为26.9%。11例针极EMG呈神经源性与肌源性混合损害,2例呈神经源性损害。结论:EMG、NCV是有价值的电生理诊断方法。确诊神经肌炎需结合临床表现和EMG结果。     

Congenital facioscapulohumeral muscular dystrophy associated with tongue atrophy and sensorineural hearing disturbance

An 18-year-old high-school boy presented facial muscle weakness since birth, and then developed wasting around the neck, shoulder girdle, upper arms, and thighs. He was born to un-consanguineous parents. His father had suffered from similar but milder muscle atrophy with predominance on the right side of the face and shoulder girdle since adolescence. His mother and his only sibling were clinically unaffected. Hearing disturbance was detected at the age of 6, and he also noted atrophy of the tongue and the bilateral thighs at the age of 10. The symptom progressed gradually. Neurological examination on admission revealed a well-developed boy (166 cm/60 kg) with a prominent facial diplegia with distinct proximal muscular atrophy of the extremities. Muscles of the tongue, neck, upper arms, shoulder and pelvic girdles, and hamstrings were markedly involved. The anterior tibial muscles were also affected, while the calf muscles were hypertrophic. High arched palate, X legs, mild lordoscoliosis were also noted. Serum CK was slightly increased (424 IU/l), and needle EMG in the extremities including the tongue revealed myopathic changes. Muscle CT demonstrated marked atrophy of the proximal muscles in the lower limbs and hypertrophy of the calf muscles. Audiogram showed bilateral sensorineural hearing disturbance. Muscle biopsy of the gastrocnemius showed myogenic as well as neurogenic changes consisting of atrophic and hypertrophic fibers with interstitial cellular infiltration, and type I fiber predominance. With these family history as well as clinical and laboratory examinations, this case could be diagnosed as "congenital facioscapulohumeral muscular dystrophy".(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of motor neuron disease with IgM gammopathy which showed anti-cerebrum antibody]

A patient, 50-year-old female, developed progressive weakness of lower extremities, and gait disturbance for 2 years. Neurological examination revealed hyperreflexia with pathological reflex, fasciculation in the limbs and tongue, muscle weakness and atrophy in distal limbs, but no sensory disturbance. Needle EMG showed neurogenic findings compatible with motor neuron disease (MND). Laboratory data showed polyclonal IgM hyperimmunoglobulinemia, positive several autoimmune antibodies including antisingle strand DNA antibody (Ab), ENAab, SS-A ab and RA. There were no antibodies for gangliosides and Myelin-associated glycoprotein (MAG), but positive antibody for 54KD protein of cerebral gray and white matter. The clinical manifestations including gait disturbance and muscle weakness, and serum IgM level were moderately improved by plasmapheresis which is considered important for consideration of causes of MND.     

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.     

Two cases of post-poliomyelitis muscular atrophy

We report two males with progressive post-poliomyelitis muscular atrophy (PPMA) who developed slowly progressive weakness and atrophy in the previously unaffected muscles 50 years after acute poliomyelitis. Case 1 is a 61-year-old male who had suffered from poliomyelitis at the age of 3 years. After recovery from acute symptoms, paralysis remained in the right face, left upper extremity and right lower extremity. Paralysis had remained unchanged until the age of 55 years, when he felt increased fatigue and progressive muscle weakness of all extremities. Neurological examination revealed muscle atrophy of the left upper and right lower extremities, and muscle hypertrophy of the left lower extremity. Deep tendon reflexes were decreased or absent. Babinski sign was negative. Reduction of his physical level and administration of anticholinesterase agents improved his feeling of fatigue. Case 2 is a 66-year-old male who suffered from poliomyelitis in his infancy, and paralysis remained in the left hand and right lower extremity. At the age of 50 years, he felt fatigue, muscle weakness of the previously unaffected legs and joint pain. Neurological examination revealed proximal muscle atrophy and weakness of lower extremities. Deep tendon reflexes were decreased and Babinski sign was negative. Needle electromyography of both cases showed typical neurogenic pattern or high amplitude and polyphasic long duration MMUs. Muscle biopsy of them from quadriceps femoris showed variability in fiber size, moderate increase of internal nuclei, fiber splitting, type grouping, grouped atrophy and scattered small angulated fibers, indicating chronic denervation and reinnervation. The clinical features and laboratory findings of the present two cases are consistent with those of PPMA.(ABSTRACT TRUNCATED AT 250 WORDS)     

肌电图肌源性损害合并神经源性损害71例临床分析

目的分析和探讨肌电图(EMG)肌源性损害合并神经源性损害的临床和电生理特点。方法检索作者医院EMG数据库,收集EMG表现为肌源性损害合并神经源性损害患者共71例,对其临床和电生理特点进行回顾性分析。结果在此组患者中,最常见的是结缔组织病,共63例(占88.7%)。其余依次为:肿瘤、进行性肌营养不良、AIDS、甲状腺功能亢进(甲亢)。在全部患者中,临床表现为近端无力者55例(占77.5%),有感觉症状体征者27例(占38.0%),肌肉萎缩者12例(占16.9%)。患者的三角肌52例(占73.2%)、股四头肌49例(占69.0%)EMG表现为肌源性损害,其中上下肢同时为肌源性损害者32例(占45.1%)。所合并存在的神经源性损害主要表现为多发性周围神经病(39例)、单神经病(27例)、颈或腰骶神经根病(5例)。结论EMG检查有助于检出临床下神经肌肉病变,电生理检查发现肌源性合并神经源性损害的同时分析肌病所合并周围神经病变类型将有助于揭示病变性质。     

Late-onset sporadic case of SPG4 (1726T>C mutant) accompanied by polyneuropathy with diabetes mellitus]

We report a 73-year-old man with SPG4. From aged 53 he had diabetes mellitus and at 64 he developed spastic paraparesis and urinary disturbance. At 70 years, he began to walk with a stick and noted abnormal sensations in bilateral feet. There was no relevant family history. Moderate spasticity with mild muscle weakness, markedly brisk tendon reflex with pathological reflexes, and mildly abnormal sensation in bilateral lower extremities, and markedly spastic gait were found. MRI showed mild C4-C7 spondylosis and L4-5 disk protrusion but no abnormality of the corpus callosum. Nerve conduction and needle EMG studies revealed various abnormalities in distal (MCV, SCV) and proximal (F-wave) peripheral nerves, but no neurogenic changes in limb muscles. We found a missense spastin gene mutation (1726T>C) that causes Leu534Pro substitution. This spastin gene mutation was novel in Japanese, but has been reported in an Italian family. The present case's neuropathy might be related to diabetes mellitus, because SPG4 is generally not associated with neuropathy. However, recent studies suggest that SPG4 patients sometimes have subclinical neuropathy, and longer disease duration may contribute to peripheral neuropathy. Further study of clinical characteristics associated with the Leu534Pro mutation will be necessary.     

A case of progressive myopathy with tubular aggregates

Tubular aggregates (TA) are unusual intramuscular structures stained basophilic on hematoxilin and eosin (HE) staining and red on modified Gomori trichrome (GT) staining. The structures are said to be originated from sarcoplasmic reticulum and are collections of tubules with double membranes on electron microscopic studies. The TA are usually seen in biopsy muscles from patients with muscle pain and cramps but without muscle weakness, periodic paralysis or alcoholic myopathy. In addition, there are five reports on families with progressive myopathy and tubular aggregates in the literature. We presented here a 48-year-old postman without any family history, who had had progressive muscle weakness for 17 years. He had never noticed pain or cramps in his muscles, not taken any particular medicine, and not had regular alcoholic beverages. There was no ptosis, facial weakness, masticatory muscle weakness or dysphagia. Muscle wasting, started from the proximal part of four extremities had progressed to the distal part of them. He could not walk on heels or toes and walked with waddling gait. He stood up with Gowers' maneuver. Serum GOT, GPT and CK were elevated. EMG showed myogenic pattern and MCV was normal. The muscle biopsies were performed; the first one taken from quadriceps femoris muscle at 42 years old showed myopathic changes including marked variation in fiber sizes, with scattered necrotic fiber splitting and TA in type 2B fibers. The second biopsy from biceps brachii muscle at the age of 48 years, showed densely proliferated fibrous tissues, marked variation fiber sizes and scattered split fibers. The TA were rarely seen and type 2B fibers were decreased in number.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic outcome of muscle biopsy

Introduction: We reviewed the diagnostic yield of muscle biopsy according to the presence or absence of muscle weakness, hyperCKemia, and electromyogaphic (EMG) abnormalities. Methods: In a retrospective study, 698 muscle biopsy reports were analyzed. Logistic regression models for myopathy and specific myopathy were fit, and receiver‐operating characteristic (ROC) curves were generated to assess prediction accuracy. The probability of finding specific myopathy was considered the main indication of a positive muscle biopsy. Results: Isolated hyperCKemia was poorly predictive of either myopathy or specific myopathy. Combined myopathic EMG, proximal weakness, and hyperCKemia were predictive. The predictability increased proportionally to the creatine kinase (CK) level in patients with proximal weakness and myopathic EMG. Cross validation showed accuracy around 70% for a probability threshold of 50%. Conclusions: The presence of hyperCKemia, proximal weakness, and myopathic EMG together were associated with highly positive diagnostic outcome of muscle biopsy. Isolated hyperCKemia had a poor diagnostic yield. Muscle Nerve 51 :662–668, 2015