A case of myotonic dystrophy showing proximal dominant muscle involvement but not myotonia]

A 45-year-old female had progressive difficulty in climbing stairs and standing from a chair for 10 years. She had binocular cataracts which were operated at the age of 42 years. On examination, she had marked muscle wasting in the proximal limbs, scapular and sternomastoid muscles. She presented as marked muscle weakness in the proximal portion of the lower extremities and moderate in the upper extremities and the legs. Deep tendon reflexes were absent in all limbs. There was no grip myotonia, or percussion myotonia of the thenar muscle and tongue. Myotonia was not elucidated even after the hands were exposed to cold water. Moreover, none of the examined muscles revealed insertion myotonic discharge on electromyography. Serum CK level was normal and IgG value decreased to 546 mg/dl. Muscle biopsy of the left biceps muscle showed the variation in fiber size, increased central nuclei and many fiber with pyknotic nuclear clumps on HE staining. Sarcoplasmic mass and ring fibers were also found on HE staining. There were a few percents of ragged-red fibers on Gomori-trichrome staining, and type 1 fiber atrophy was found on pH 4.5 ATP-ase staining. The expansion of lymphocyte CTG trinucleotide repeats in the myotonin protein kinase gene was about 733, so that she was diagnosed as having myotonic dystrophy (MD). MRI of skeletal muscles exhibited marked atrophy especially in the femoral region and the biceps muscle. This patient had the proximal dominant muscle weakness, and absent myotonia even on electromyographic examination, which are unusual clinical features of adult onset MD.     

Two sisters with dysferlinopathy manifesting different clinical phenotypes]

We report two sisters with dysferlinopathy who manifested different clinical phenotypes. A 22-year-old female (patient 1) noticed of difficulty in running at the age of 13 years, and since then weakness of the lower extremities has progressed slowly. She had typical features of Miyoshi myopathy (MM); i.e., young adult onset, dominant involvement of calf muscles and markedly elevated serum creatine kinase (CK). Her 19-year-old sister (patient 2) first noticed of weakness in lower extremities at age 12 years. On neurological examination, she had proximally dominant muscle weakness, consistent with limb girdle muscular dystrophy type 2B (LGMD2B); serum CK level was also markedly elevated. On MRI study of muscle, patient 1 showed fatty degeneration of calf muscles, whereas patient 2 showed no abnormality in quadriceps and calf muscles. Immunohistochemistry of the muscle biopsy specimens using anti-dysferlin antibody showed deficiency of this protein in sarcolemma. There have been only a few reports of sibling cases of dysferlinopathy whose clinical phenotypes are different. These sibling cases may have important suggestion on the mechanism(s) of phenotypic variation of dysferlinopathy.     

A case of sarcoid myopaty with external ocular muscle involvement--diagnosis and follow-up study with 99mTc pyrophosphate scintigraphy]

A 62-year-old woman was admitted to our hospital because of diplopia and muscular weakness. She had been diagnosed as having sarcoidosis histologically by skin biopsy 5 years before. Although neither CT nor MRI could detect the granulomas, 99mTc-pyrophosphate scintigraphy successfully detected the involvement of sarcoidosis not only in the skeletal muscles but also in the external ocular muscles. After treatment with prednisolone, the symptoms markedly subsided and increased uptake of radionucleotide disappeared. Although 67Ga scintigraphy is also known to be useful in investigating the sites affected by sarcoidosis throughout the body, it was not effective in detecting the involvement of external ocular muscle due to the physiological uptake of 67Ga to the lacrimal grands. While the granulomas are frequently observed histologically in skeletal muscles, usually they are not associated with muscle symptoms. In our study 99mTc-pyrophosphate scintigraphy has proven to be useful in investigating the nodular lesions in skeletal muscles of sarcoidosis than 67Ga scintigraphy.     

Adult form of acid maltase deficiency presenting with pattern of muscle weakness resembling facioscapulohumeral dystrophy]

We report a 61-year-old female patient with adult form of acid maltase deficiency showing many clinical similarities to facioscapulohumeral muscular dystrophy (FSHD). She developed difficulty in raising her right arm in her thirties followed by leg weakness. She had the typical features of FSHD, including bilateral scapular winging sparing the levator scapulae and deltoid muscles, and Beevor's sign. Muscle involvement was asymmetrical. Facial muscles were not affected, while the neck flexor was weak. No muscle shortening or joint contracture was observed. On muscle CT, the lumbar paravertebral, gluteal and thigh muscles were replaced by adipose tissue, while the rectus femoris, gracilis, and sartorius muscles were spared. Serum creatine kinase level was not elevated. Muscle biopsy showed some vacuoles and many granular inclusions with high acid phosphatase activity. Acid maltase activity was very low in both muscle and cultured skin fibroblasts. Absence of shortening of affected muscles appears to be the characteristic finding suggesting metabolic myopathies with minimal fibrosis, rather than FSHD.     

Polymyositis with marked paravertebral muscle atrophy in patients with primary biliary cirrhosis]

We reported two patients with polymyositis (PM) associated with primary biliary cirrhosis (PBC) who noticed head-drop as the incipient symptom. Muscle computed tomography showed marked hypodensity in the paravertebral muscles as compared with limb muscles. Patient 1, a 48-year-old female, was admitted in our hospital for the examination because of her neck and proximal limb muscle weakness, increasing fatigability, and abnormal serum liver and muscle enzyme levels. She felt her throat was so dry at age 39, and she noticed weight loss at age 41 and head-drop at age 42. A diagnosis of PM was made from symmetrical proximal limb muscle weakness, elevated creatine kinase (CK) level, and the electromyographic and muscle biopsy findings. Her illness was also diagnosed as PBC because of the increased serum alkaline phosphatase and IgM immunoglobulin levels, and liver biopsy findings. The anticentromere antibody titer was positive, though the antimitochondrial antibody titer negative. The HLA typing was DR 4, DR 8, DR53, DQ 4, DQ 6, DRB 1 (0405/0803). She was placed on 60 mg of prednisolone/day for PM and 300 mg of ursodeoxycholic acid/day for PBC. Patient 2, a 49-year-old female, presented with proximal limb muscle weakness and head-drop. Serum CK, alkaline phosphatase and IgM immunoglobulin levels were increased. The antimitochondrial antibody titer was positive. She began to have 60 mg of prednisolone/day, and 50 mg of azatioprine/day and 300 mg of ursodeoxycholic acid/day were subsequently added. PM associated with PBC seems to be rare, because only 21 cases have been described in literature. In those patients, marked paravertebral muscle atrophy has never been described. Further study is necessary to examine whether or not the preferential paravertebral muscle involvement is a striking and diagnostic finding for PM with PBC.     

Clinical phenotype, muscle MRI and muscle pathology of LGMD1F

Of the seven autosomal dominant genetically distinct forms of LGMD so far described, in only four the causative gene has been identified (LGMD1A-1D). We describe clinical, histopathological and muscle MRI features of a large Italo-Spanish kindred with LGMD1F presenting proximal-limb and axial muscle weakness. We obtained complete clinical data and graded the progression of the disease in 29 patients. Muscle MRI was performed in seven patients. Three muscle biopsies from two patients were investigated. Patients with age at onset in the early teens, had a more severe phenotype with a rapid disease course; adult onset patients presented a slow course. Muscle MRI showed prominent atrophy of lower limb muscles, involving especially the vastus lateralis. Widening the patients population resulted in the identification of previously unreported features, including dysphagia, arachnodactyly and respiratory insufficiency. Muscle biopsies showed diffuse fibre atrophy, which evolved with time, chronic myopathic changes, basophilic cytoplasmic areas, autophagosomes and accumulation of myofibrillar and cytoskeletal proteins. The LGMD1F is characterized by a selective involvement of limb muscles with respiratory impairment in advanced stages, and by different degrees of clinical progression. Novel clinical features emerged from the investigation of additional patients.     

A patient with sarcoidosis needed differential diagnosis from motor neuron disease]

A 50-year-old woman lost about 10 kg of body weight within two months. Thereafter, she developed dysphagia and dysphonia. She visited our hospital and presented with a weak elevation of the soft palate, fasciculation of the tongue, hoarseness of voice, muscle weakness of the neck and extremities, and a decrement in vital capacity. She was admitted with a provisional diagnosis of motor neuron disease. The results of laboratory examinations showed an elevation in serum lysozyme and liquor protein levels, and pleocytosis in the liquor. Needle electromyography showed neurogenic changes, and bilateral hilar lymphadenopathy was revealed by computerized tomography. A biopsy specimen was excised from lymph nodes near the right anterior scalene muscle, which showed noncaseating granulomas consistent with sarcoidosis. All her symptoms improved after steroid administration. Such patients can be treatable with steroids. Moreover, the differential diagnosis from motor neuron disease is important.     

Detection of immune complexes in the sera and around the muscle fibers in a case of myasthenia gravis and polymyositis

A case of myasthenia gravis accompanied with polymyositis and malignant thymoma, detected immune complexes in the sera and around the muscle fibers, was described. A 37-year-old woman was admitted to Shinshu University Hospital in September, 1987 because of dyspnea, dysphagia and muscle weakness. She first noticed her right blepharoptosis 3 weeks before admission. Weakness of all four limbs and myalgia of lower extremities were noticed one week later. These symptoms got worse and nocturnal dyspnea, dysphagia and easy fatigability at mastication appeared. On admission, she looked ill and neurological examination revealed left blepharoptosis, bilateral facial weakness, weakness of all four limbs, more prominent in proximal muscles and tenderness of lower extremities. Edrophonium test was positive, improving her muscle weakness. Laboratory examination revealed the elevated serum levels of CK, the increased titre of circulating immune complexes and high titres of acetylcholine receptor antibodies and anti-skeletal muscle antibodies. Electromyographic study showed myogenic pattern and Harvey-Masland test revealed waning at low frequency stimulation. Muscle biopsy showed marked perivascular infiltration of lymphocytes, accompanied by phagocytosis and interstitial fibrosis. IgG deposits were shown around the muscle fibers exclusively around the infiltrates of mononuclear cells. Granular deposits of C3 were also shown specifically around the muscle fibers exclusively around the infiltrates of mononuclear cells. Thymectomy was performed on September 21, 1987. Invasion of thymoma, predominantly lymphocytic type, to right lung and pericardium was observed histologically. After thymectomy, she got better. Immunological data and immunohistochemical examination of the present case suggest that in the case of myasthenia gravis accompanied with polymyositis and malignant thymoma, immune complexes may play a primary role on the pathogenesis of myositis.     

A case with severe respiratory muscle weakness due to chronic myositis associated with PBC]

We report a 37-year-old woman with slowly developing muscular weakness for 2 years following insidious stiffness of calf muscle. Serum CK was elevated up to 4,207 IU/l. She presented sleepiness, weakness of proximal and truncal muscles and systemic muscular atrophy. While she had not experienced dyspnea, her arterial blood gas analysis revealed extreme hypoxia and hypercapnea due to weakness of respiratory muscles. Echocardiogram showed thinness and hypokinesis of left ventricular wall, and arrhythmia was pointed out by holter ECG. Needle elctromyogram of the proximal muscles exhibited polyphasic units with low amplitude. Muscle biopsy showed degeneration and necrosis of muscle fibers as well as regeneration. Mild infiltration of inflammatory cells was shown. Serological examination showed positive antimitochondrial M2 antibody, especially specific for primary biliary chirrhosis (PBC). She was diagnosed as chronic myositis associated with PBC. Four cases of idiopathic myositis with severe weakness of respiratory muscle, associated with PBC had been reported. These cases and our present case share the similar feature in respect of insidious or chronic course and resistance to therapy. In our present patient, respiration had been supported by BiPAP and she has been successfully improving slowly by oral steroid following 4 courses of methylprednisolone pulse therapy.     

A thyrotoxic myopathy accompanied with unusual muscle symptoms and MRI muscle findings]

We report a patient with thyrotoxic myopathy associated with unusual muscle symptoms. A 29-year-old man developed hyperhidrosis, diarrhea, increase in appetite, and excitability in July, 1999. In August, he experienced muscle stiffness in bilateral lower extremities after maintaining postures such as driving a car or sitting on a chair. He was admitted to our hospital, in January, 2000. On physical examination, goiter was noted. Neurological examination was normal except for proximal muscle weakness. Laboratory test showed elevated free T3 and free T4, decreased TSH. TSH receptor antibody was increased. MRI of lower extremities revealed atrophy of bilateral biceps femoris. Muscle strength increased gradually after an oral administration of thiamazole 30 mg/day, and muscle stiffness disappeared. The clinical features of this patient and differential diagnosis were discussed.     

Progressive weakness with respiratory failure in a patient with sarcoidosis

A 29-year-old African American woman with an 8-year history of biopsy-proven renal sarcoidosis and end-stage renal disease requiring hemodialysis was admitted to the hospital with progressive weakness and shortness of breath for 2 months. Eight months prior to admission, she was prescribed 15 mg of prednisone twice a day and 200 mg of hydroxychloroquine sulfate twice a day for hypercalcemia and elevated angiotensin-converting enzyme level. As her laboratory abnormalities improved, the prednisone dose was gradually decreased, and hydroxychloroquine was continued. Six months earlier, she noticed numbness in her feet and progressive loss of muscle bulk in her feet and hands. She also noticed difficulty reaching overhead, getting out of a chair, and climbing stairs. She denied any pain or muscle cramps. Results of electrophysiological tests at that time, which included nerve conduction studies and needle electromyography, revealed moderately severe axonal sensorimotor polyneuropathy. Her weakness worsened and so she was admitted to the hospital and subsequently transferred to our facility for further management.     

McArdle's disease without typical symptoms

A 25-year-old female with McArdle's disease was reported. She had no characteristic symptoms for McArdle's disease such as muscle cramp and brown urine, but had general fatiguability from childhood. On examination, she showed no neurological abnormalities including muscle atrophy and weakness. On laboratory examination, serum creatinine kinase (CK) level was elevated, though serum lactic acid level remained unchanged after the ischemic forearm exercise test. Muscle biopsy from the biceps brachii showed almost completely absent phosphorylase activity both histochemically and biochemically. Thus, she was diagnosed as having McArdle's disease. The skinned fiber test of the muscle showed no enhanced Ca induced Ca release (CICR), and serum VLDL level was normal. Her 27-year-old elder brother had similar clinical symptoms and serological abnormalities and may also have McArdle's disease, although muscle biopsy was not performed. A possibility of McArdle's disease should be considered when we encounter a patient who has only general fatigue and high serum CK level.     

A family with oculopharyngeal muscular dystrophy with (GCG)9 expansion in which a sister had neck as well as proximal and her brother proximal lower limb muscle weakness]

We report a 58-year-old woman (patient 1) and her 60-year-old brother (patient 2) with autosomal dominant oculopharyngeal muscular dystrophy. Patient 1 first noticed blepharoptosis and neck weakness at age 55. On neurological examination, she showed bilateral blepharoptosis and weakness in the neck and upper proximal limbs. Serum creatine kinase (CK) level was slightly elevated. Her older brother first noticed blepharoptosis and lower limb weakness at age 51. On neurological examination, he showed bilateral blepharoptosis, slight ophthalmoparesis and bilateral iliopsoas muscle weakness. Serum CK level was normal. Esophageal fluoroscopy disclosed dysfunction of the constrictor pharyngeal muscles. Muscle biopsy of them showed myopathic changes with rimmed vacuoles. The (GCG)9 mutation in the poly (A) binding protein 2 gene was identified, which was the same as seen in the large French-Canadian kindred in Quebec in Canada. The clinical phenotype in patient 2 is similar to that of French-Canadian patients but it in patient 1 is different in distribution of muscle weakness.     

Overloading to neck extensor muscles is an aggravating factor to induce further neck drop in isolated neck extensor myopathy (Katz). A case report]

A 78-year-old woman was hospitalized because of progressive anterior neck drop over 4 months prior to admission. She was normal except for mild weakness of her neck, trapezius and biceps brachii muscles. EMG revealed mild myopathic changes in the neck extensors, trapezius, deltoid and sternocleidomastoid muscles. Bilateral splenius capitis muscles had high intensities on T2-weighted and STIR pulse-sequenced MRI. However, there were no inflammatory changes in the right splenius muscle biopsy. Accordingly, the abnormal MRI finding seems not to result from an inflammatory process but from an physiological increase of intracellular water content due to sustained muscle contraction. Because apparent neuromuscular diseases responsible for neck drop were excluded, her clinical features met the criteria of isolated neck extensor myopathy (INEM, Katz). After strict bed-rest for one month, her neck drop improved dramatically. When she returned to the previous life style after discharge, her symptoms of the neck drop reappeared. Although the cause of INEM remains unclear, the present case indicates that the condition is reversible at least in the early stage of the disease, and the overloading to the neck extensor muscles is an aggravating factor of the neck drop in INEM.     

Diagnosis of inflammatory myopathy; usefulness of 99mTc MDP scintigraphy and muscle MRI for determination of affected sites]

We studied the effectiveness of 99mTc-MDP (methylendiphosphate) scintigraphy in imaging inflammatory myopathy. The three subjects including 1 male and 2 female patients had high creatine kinase (CK) levels and proximal dominant muscle weakness. In whole body muscle surveillance by 99mTc-MDP scintigraphy, abnormal 99mTc-MDP accumulation was found in the extremities of all patients. The sites with high 99mTc-MDP accumulation showed high intensity on T2 weighted MR imaging, suggesting an inflammatory process. Muscle biopsy was performed on two patients from the muscles with the abnormal MRI findings, which showed the diagnostic finding of inflammatory changes. Because muscle involvement in inflammatory myopathy differs from muscle to muscle, it is sometimes difficult to choose appropriate muscle biopsy sites for diagnostic purposes. Affected muscles are more easily identified by using 99mTc-MDP muscle scintigraphy and muscle MRI, therefore, a correct diagnosis and choice of biopsy site can be made. 99mTc-PYP scintigraphy is permitted for use in myocardial infarction alone and 111In-antimyosin scintigraphy is not available in Japan. Therefore, we recommend 99mTc-MDP scintigraphy for diagnosis of inflammatory myopathy and for determination of muscle biopsy sites.     

Lipid storage myopathy in von Gierke's disease: a case report.

An 18-year-old girl with von Gierke's disease associated with a lipid storage myopathy is reported. The diagnosis of von Gierke's disease was made from decreased activity in glucose-6-phosphatase in the jejunal biopsy specimen. Neurologically she showed generalized hypotonia of the muscles, atrophy of bilateral proximal muscles of the lower extremities, weakness in neck flexors, deltoid and lumbar girdle muscles, and a positive Gower's sign. Muscle biopsy from flexor femoris muscle revealed fatty deposition in type 1 fibers and atrophy of type 2 fibers and the diagnosis of an accompanying lipid storage myopathy was made. This case also had a ventricular septal defect confirmed by right cardiac catheterization.     

Sarcoid myopathy presenting with diaphragm weakness

Sarcoidosis involving muscle occurs frequently, but it is infrequently symptomatic. The clinical, electromyographic, and histologic features of sarcoidosis involving muscle in a 63-year-old woman presenting with diaphragm weakness are described. An electromyogram revealed widespread myotonia and an inflammatory myopathic process, suggestive of adult-onset acid maltase deficiency disease. Muscle biopsy showed noncaseating granulomas consistent with sarcoidosis. Clinical improvement followed the initiation of oral prednisone therapy. This case illustrates that muscular sarcoidosis may mimic adult-onset acid maltase deficiency in both its clinical and electromyographic features. © 1993 John Wiley & Sons, Inc.     

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.     

A case of facioscapulohumeral muscular dystrophy with infantile spasms, sensorineural deafness and retinal vessel abnormality

We report an 18-year-old female with facioscapulohumeral dystrophy (FSHD), who had sensorineural deafness, retinal vessel abnormality, mental retardation, and epilepsy. She had infantile spasms at 6 months of age. Muscle atrophy and weakness of facial muscles were first noticed at 3 years of age. From 10 years of age, she had rapidly progressive generalized muscle weakness especially of facial, neck and truncal muscles with marked lordosis. Although mental retardation is commonly complicated with FSHD, infantile spasms or epilepsy has never been reported. Not only mental retardation but epilepsy may be one of the central nervous system symptoms in a systemic disorder, FSHD.     

强直性肌营养不良Ⅰ型临床、病理、骨骼肌磁共振特点

目的总结11例强直性肌营养不良Ⅰ型(DM1)患者的临床、病理和双下肢肌肉受累的特点。方法回顾性分析2012年01月至2020年10月就诊于南京鼓楼医院神经内科的11例DM1患者的临床、骨骼肌活检病理及5例双下肢骨骼肌磁共振的特点。结果11例患者均有不同程度的肌强直、伴有肌无力/肌萎缩症状,肌无力/肌萎缩远端重于近端。骨骼肌病理特点:10/11例患者可见Ⅰ型肌纤维轻度萎缩,部分患者可见核内移、核聚集、肌浆块现象。双下肢肌肉磁共振:5例患者双下肢远端脂肪浸润重于近端,双侧肌肉受累程度不对称,大腿肌肉脂肪浸润以股中间肌最严重,小腿肌肉以腓肠肌、比目鱼肌、腓骨长肌最严重。结论骨骼肌磁共振对诊断强直性肌营养不良Ⅰ型有重要的提示意义。