A case of rigid spine syndrome with rimmed vacuole

A case of rigid spine syndrome associated with rimmed vacuoles in muscle biopsy is reported. A 36-year-old man was admitted to our hospital because of gait disturbance and limited mortality of the spine. His family was free from any neuromuscular disorders. He was born in normal pregnancy and delivery. His physical development was normal. At age 7, he was unable to run fast. At age 36, he had right hemiparesis and dysarthria. He was diagnosed as cerebral infarction of the left basal ganglia by brain CT. Neurological examination revealed moderate proximal dominant muscular atrophy and weakness. His spine was straight, showing loss of physiological cervical and lumbar lordosis. The neck flexion was limited but the extension was full. And he had contracture of bilateral ankle joint. Laboratory findings were all normal. The electrocardiogram showed negative T wave in V4, V5 and QT interval elongation. The echocardiogram showed diffuse decrease of ventricular wall motion. Respiratory function test revealed decrease of vital capacity. Arterial blood gases on room air showed that the PaO2 and PaCO2 were 70 mmHg and 49 mmHg, respectively. The findings of electromyogram were compatible with myopathic change. Biopsy specimen of the biceps brachii muscle showed marked variation in fiber size, type 1 fiber predominancy and atrophy, and type 2B fiber deficiency. Numerous rimmed vaculoes were found in the same muscle. Four cases of the rigid spine syndrome with rimmed vacuoles have been described. Among them, three patients died in young ages and two suffered from constrictive respiratory failure. In rigid spine syndrome with rimmed vacuole formation, the cardiac and respiratory problems must be taken account intensively.     

Congenital fiber type disproportion

Type I muscle fiber atrophy in childhood can be encountered in a variety of neuromuscular disorders. Congenital fiber type disproportion (CFTD) is one such condition which presents as a nonprogressive muscle weakness. The diagnosis is often made after excluding other differential diagnostic considerations. We present a 2-year-9-month-old full term boy who presented at 2 months with an inability to turn his head to the right. Over the next couple of years, he showed signs of muscle weakness, broad based gait and a positive Gower’s sign. He had normal levels of creatine kinase and normal electromyography. A biopsy of the vastus lateralis showed a marked variation in muscle fiber type. The adenosine triphosphate (ATP)-ase stains highlighted a marked type I muscle atrophy with rare scattered atrophic type II muscle fibers. No abnormalities were observed on the nicotinamide adenine dinucleotide (NADH), succinate dehydrogenase (SDH) or cytochrome oxidase stained sections. Ragged red fibers were not present on the trichrome stain. Abnormalities of glycogen or lipid deposition were not observed on the periodic acid–Schiff or Oil-Red-O stains. Immunostaining for muscular dystrophy associated proteins showed normal staining. Ultrastructural examination showed a normal arrangement of myofilaments, and a normal number and morphology for mitochondria. A diagnosis of CFTD was made after excluding other causes of type I atrophy including congenital myopathy. The lack of specific clinical and genetic disorder associated with CFTD suggests that it is a spectrum of a disease process and represents a diagnosis of exclusion.     

Two brother cases of late-onset familial amyloidotic polyneuropathy in Kyoto]

Measurement of variant Met30 transthyretin is diagnostic for a patients with familial amyloidotic polyneuropathy (FAP) type I. The elder brother first noticed numbness of the feet at 64 years of age, and developed weakness of the legs. A few years later, he noticed numbness of the hands, and he was admitted to the hospital at 67 years of age. He was emaciated and had hoarseness and macroglossia. He had moderate muscle atrophy and weakness of all extremities with distal predominance. Deep tendon reflexes were hypoactive in the upper limbs and absent in the lower limbs. There was marked sensory loss of pain and temperature in all 4 limbs distally, and position sense was also impaired. He had mild orthostatic hypotension, severe cardiomegaly and arrhythmia. The younger brother noticed cold sensation of the feet and sexual impotence at 59 years of age. Two years later, he had numbness of the feet and developed weakness of the legs. At 65 years of age, he was admitted to the hospital because of the micturition syncope. He was emaciated and had macroglossia. He had moderate muscle atrophy and weakness of all extremities with distal predominance. Deep tendon reflexes were absent. There was marked sensory loss in the extremities which was predominant in pain and temperature. He had severe orthostatic hypotension (112/70 mmHg in supine position, 50/30 mmHg on standing). Plasma NE value was low and showed poor response to standing. He had neither cardiomegaly nor arrhythmia. Their parents were supposed to have no neurological symptom and were not related with any other Japanese foci of FAP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Congenital fiber type disproportion--30 years on

Thirty years ago, M. H. Brooke coined the term "congenital fiber type disproportion" (CFTD) to describe 12 children who had clinical features of a congenital myopathy and relative type 1 fiber hypotrophy on muscle biopsy. It is now clear that this histological pattern can accompany a wide range of neurological disorders, leading to disillusionment with CFTD as a distinct nosological entity. To determine whether the CFTD has clinical utility as a diagnostic entity, we have reviewed the literature for cases of type 1 fiber hypotrophy and have used strict exclusion criteria to identify 67 cases of CFTD. Most patients presented at birth with weakness and hypotonia, had normal intelligence, and followed a static or improving clinical course. In 43% of families, more than 1 individual was affected. Failure to thrive was common and 25% of patients had contractures or spinal deformities. Bulbar weakness and ophthalmoplegia were less common and cardiac involvement was rare. Twenty-five percent followed a severe course and 10% had died at the time of reporting, all from respiratory failure. Ophthalmoplegia and facial and bulbar weakness were significantly associated with a poorer prognosis. The relatively homogeneous phenotype supports the retention of CFTD as a distinct diagnostic entity and familial occurrence suggests a genetic basis. Regarding the diagnosis of CFTD, we found no strong evidence that the minimum difference between type 1 and type 2 fiber sizes should be increased from 12% to 25%. We also list the other reported causes of relative type 1 fiber hypotrophy to aid their exclusion from CFTD.     

先天性肌纤维类型不均的临床表现和病理特点（附1例报道）

目的：探讨先天性肌纤维类型不均（CFTD）的临床表现和病理特点。方法：回顾复旦大学附属华山医院神经科收治的1例CFTD患者的临床表现和肌肉病理改变,并结合国外文献报道的3组共21例病例进行分析比较。结果：21例CFrD患者中,男11例,女10例。平均发病年龄为2．84岁,约28．6％的患者有家族史。除四肢无力及肌张力低下外,伴面肌无力者42．9％,喂养困难者19．0％,呼吸肌受累者38．1％,约1／3患者有高腭穹、脊柱侧凸、关节挛缩等骨骼畸形,所有病例认知功能均正常。约71．43％的患者病情稳定,28．6％的患者病情缓慢加重。与文献报道比较,本文所报道的病例临床表现具有肌无力和肌萎缩进展缓慢,而呼吸肌和骨骼不受累等肌营养不良样的特点。结论：CFTD作为先天性肌病的一种,可有肌营养不良样的临床表现,明确诊断有赖于肌肉活检。     

A case of acute quadriplegic myopathy]

A 22-year-old man developed unconsciousness, severe quadriplegia and muscle atrophy, and had markedly elevated serum creatine kinase levels after using the high-dose steroid and nondepolarizing neuromuscular blocking agents during the course of sepsis and DIC. On neurological examination, he was lethargic. The patient had generalized muscle weakness and wasting, and diminished deep tendon reflexes. He weakly responsed to painful stimuli on the legs. The motor nerve conduction study demonstrated decreased CMAP (compound muscle action potential) amplitudes. Motor and sensory nerve conduction velocities and their distal latencies were normal. Muscle biopsy revealed marked muscle fiber atrophy predominantly in type 2 fibers and numerous basophilic and a few necrotic fibers. Some atrophic fibers had decreased to absent myosin adenosine triphosphatase activity in their center. Accordingly, he was diagnosed as having acute quadriplegic myopathy (AQM), which has been reported mainly in Western countries. The mechanism of muscle fiber degradation in this myopathy is still unknown. On immunohistochemical analysis to our patient, enzyme activities of various proteases such as calpain, cathepsin B, and proteasomes were increased in the sarcoplasm, especially in the atrophic fibers. We suggest that lysosomal cathepsin, nonlysosomal calpain, and ATP-ubiquitin-proteasome proteolytic pathways participate in muscle fiber degradation in AQM.     

A case of polymyositis with repeated dysphagia and muscle weakness associated with peculiar findings of skin

A case of polymyositis with repeated dysphagia and muscle weakness associated with peculiar findings of skin was reported. The patient was a 67-year-old man. His birth and development was normal. There was no family history of neuromuscular disease. On 26th March 1987 he was admitted to a hospital because of dysarthria and dysphagia after fever and diagnosed as having viral myositis. His conditions improved spontaneously with bed rest and he left hospital on 14th April. On 23rd April he had chill and sore throat with fever. On 27th he was admitted to the same hospital because of dysarthria and muscle weakness of the proximal portion of the upper limbs. These symptoms also improved with bed rest. He had repeated these symptoms several times and then he was admitted to our hospital on 12th June. On examination he showed the skin pigmentation under the right eye and the eruption in the back of hands and the buttocks. Muscle weakness was observed in the proximal portion of the upper limbs and the neck flexor. Laboratory tests in admission were as follows: sGOT 49 mU/ml, sGPT 104 mU/ml, LDH 1064 mU/ml, CPK 565 mM/ml, aldolase 25.2 IU/1/37 degrees C. Electromyography showed the typical myogenic changes and biopsy of left biceps brachii revealed inflammatory cells in the muscle fiber which are specific to polymyositis. Immuno-histochemical study is performed to analyse the subpopulation of mononuclear cells in biopsied muscle and skin. Mononuclear cells infiltrated into perimysium, endomysium and epidermis were positive for T11 and T8, but less positive for T4, B1 and Leu11. On the basis of these findings he was diagnosed as having "polymyositis syndrome".     

A case of diabetic polyneuropathy complicated with entrapment neuropathy of the bilateral ulnar nerves due to osteoarthrosis at the elbow]

We report a 61-year-old man with diabetic polyneuropathy and bilateral ulnar nerve palsy due to osteoarthrosis in the elbow. He was diagnosed as having non-insulin dependent diabetes mellitus (DM) at 40 years of age. At 56 years of age, he developed muscle atrophy and weakness predominantly in the distal parts of his upper limbs. A neurological examination showed him to have severe atrophy and weakness in the muscles innervated by the ulnar nerve bilaterally. He also had paresthesia on the distal parts of all four limbs. Superficial and deep sensory deficits were observed in the lower limbs. A motor nerve conduction study showed a marked reduction in the motor conduction velocity as well as in the amplitude of the action potentials of both ulnar nerves. Roentgenograms of the elbow joints and grooves for the ulnar nerve revealed marked osteophyte formation bilaterally. The bilateral ulnar nerve palsy was thus considered to be due to the entrapment of the nerve by the osteophyte. Since several studies have suggested the existence of a relationship between DM and osteoarthropathy, it is important to check for the possible presence of osteoarthrosis in cases of diabetic neuropathy complicated with entrapment neuropathy.     

A case of cervical spondylotic amyotrophy resembling post-polio syndrome]

We reported a 62-year-old man with cervical spondylotic amyotrophy, in whom differentiation from post-polio syndrome was required. At the age of 3, the patient developed acute anterior poliomyelitis that caused muscular atrophy and muscle weakness in the left arm and bilateral lower limbs. At the age of 61, after approximately 58 years of symptomatic stabilization, the patient newly developed muscular atrophy and muscle weakness localized in the triceps muscle of the left arm. Since no sensory disturbance was noted, post-polio syndrome was initially suspected. However, MRI and myelo-CT demonstrated left side compression of the spinal cord at the level of the 6th cervical spine. Therefore, the patient was diagnosed as having cervical spondylotic amyotrophy, and the progression of the disease was prevented by having the patient rest. Since this patient had a history of acute anterior poliomyelitis, the number of anterior horn cells might have been decreased before he developed cervical spondylosis. Therefore, the patient might have shown clinical symptoms of cervical spondylotic amyotrophy mainly consisting of anterior horn disturbance and scarce sensory disturbance.     

Sequential muscle biopsy changes in a case of congenital myopathy

Muscle biopsies at age 7 months in a set of dizygotic male twins born floppy showed typical features of congenital fiber-type disproportion (CFTD). One of the twins died at age 1 year due to respiratory complications. The second one subsequently developed facial diplegia and external ophthalmoplegia. He never walked, remained wheelchair bound, and required continuous ventilatory support. He underwent repeat biopsies at ages 2 and 4, which showed many atrophic type 1 muscle fibers containing central nuclei and severe type 2 fiber deficiency compatible with centronuclear myopathy (CNM). Two-dimensional gel electrophoresis of muscle showed decreases of type II myosin light chains 2 and 3, suggestive of histochemical type I fiber deficiency. The progressive nature of morphological changes in one of our patients cannot be explained by maturational arrest. Repeat biopsies in cases of CFTD with rapid clinical deterioration may very well show CNM. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 561–569, 1997.     

Infantile cytochrome c oxidase deficiency with neonatal death

A newborn male presented with severe respiratory insufficiency, generalized muscle weakness, and lactic acidemia. Immediately after admission, he was placed on a respirator because of respiratory arrest. He deteriorated rapidly and died 75 hours after birth. There was notable variation in fiber size and an increased number of type 2C fibers in the quadriceps femoris muscle obtained at autopsy; however, no ragged-red fibers were observed with modified Gomori trichrome staining. Markedly decreased cytochrome c oxidase activity was demonstrated in skeletal muscle by biochemical and histochemical studies, while cardiac muscle demonstrated normal cytochrome c oxidase activity. Mitochondrial myopathy should be considered in the differential diagnosis of patients with neonatal respiratory distress syndrome.     

Clinical and pathological studies on nemaline myopathy in adulthood]

We examined 22 biopsied muscles from adult patients who had the histopathological characteristics of nemaline myopathy. In the first group, 13 patients had muscle weakness and/or skeletal abnormalities, such as high-arched palate, pes cavus and scoliosis which are often accompanied with the congenital nemaline myopathy. Their appropriate diagnosis had never been made until muscle biopsy was done, because of benign clinical course. In the second group, the symptoms of nine patients became manifest in adulthood and failed to show typical skeletal abnormalities. However, six muscle biopsies showed the histopathologic characteristics of congenital nemaline myopathy; abnormal fiber type distribution including type 1 fiber predominancy, type 1 fiber atrophy and type 2B fiber deficiency. Three patients remained in good health until adulthood when they developed muscle weakness with pathologic findings of nemaline myopathy. Accordingly, nemaline myopathy in adulthood can be categorized into three forms; the first two forms have clinical and pathologic evidence of the congenital benign form, whereas the symptoms are too mild to be noticed. The third form is not a hereditary disorder which may result from autoimmune pathophysiology.     

Myotonic dystrophy and lipoma: a new association

A 58-year-old man developed muscle weakness and had more than 1,000 CTG repeats in the myotonin protein kinase gene. He was diagnosed as having myotonic dystrophy. At the time of diagnosis, a large tumor was detected in his abdominal cavity on CT scan examination. He died from pneumonia 6?years later. At autopsy, the abdominal tumor was diagnosed as a lipoma. Several types of tumor have been reported to be associated with myotonic dystrophy type 1; however, this is the first detailed clinical case demonstrating the possible relationship between myotonic dystrophy and lipoma.     

Nemaline myopathy with type 2 fiber predominance; a case report]

A 4-year-old boy was admitted to our hospital because of dyspnea and muscle-weakness. His developmental milestones were delayed. His face was long with opened mouth. He spoke with nasal voice. He had proximally dominant muscle weakness and his deep tendon reflexes were absent. Laboratory examination revealed normal serum creatine kinase level and a myopathic EMG pattern. Blood gas analysis revealed metabolic acidosis with PH 7.35, PCO2 55.4 mmHg, PO2 62.4 mmHg, BE 3.0, probably from the metabolic acidosis by respiratory muscle weakness. In the biopsied left biceps brachii muscle, there were scattered fibers with nemaline bodies and abnormal fiber type distribution; type 1, 2 A, 2 B and 2 C fibers comprised 7%, 70%, 21% and 2% respectively. Small type 1 fibers and type 1 fiber predominance are the characteristic and common histochemical findings in nemaline myopathy. Accordingly, type 2 fiber predominance in the present patient is a unique, rare phenomenon. The finding might result from a preferential loss of type 1 motoneurons or muscle fiber type transformation from type 1 to type 2 fibers due to a certain abnormal neuronal influence on developing muscles.     

A patient with vitamin E deficient, myopathy presenting with amyotrophy]

We report a 61-year-old man with vitamin E deficiency, presenting with, myopathy as an only clinical symptom. In 1997, at 59 years of age, he noted mild proxymal-muscle weakness and atrophy in the four extremities, nine years after he received a Billroth II partial gastrectomy for a gastric ulcer. His muscle weakness slowly exacerbated, and he was admitted to our hospital in 1999. On admission, neurological examination confirmed mild proximal-muscle weakness and atrophy in the four extremities. Intelligence, cranial nerves, coordination, sensation and tendon reflexes were all normal. Laboratory examination showed normochromic anemia (Hb 9.9 g/dl, Ht 30.9%, MCV 97.5 fl, MCHC 31.2 pg), hypoproteinemia (5.0 g/dl), and hypocholesterolemia (107 mg/dl). The levels of serum CK, lactate and pyruvate were normal. The serum vitamin E level was markedly reduced (0.17 mg/dl; normal 0.75-1.41). Cerebrospinal fluid was normal. Nerve conduction, sensory evoked potentials (SEP), electromyography (EMG), head CT and electroencephalography (EEG) were all normal. Muscle biopsy from the right deltoid muscle showed both mild myogenic and neurogenic changes. Remarkably, type 1 muscle fiber predominance and granular accumulation of autofluorescent lipofuscin granules in the muscle fibers were found. These pathological findings were compatible with those of vitamin E-deficient myopathy. Thus, he was diagnosed as having vitamin E-deficient myopathy, which was confirmed by apparent effective supplementation of vitamin E. Interestingly, our present case did not show any other neurological manifestations such as deep sensory disturbance, sensory ataxia or polyneuropathy. A long-term workload due to hard physical labor and smoking in our patient may have accelerated oxidative muscle damage, resulting in amyotrophy mainly due to vitamin E deficient myopathy.     

Actin mutations are one cause of congenital fibre type disproportion

We report three heterozygous missense mutations of the skeletal muscle alpha actin gene (ACTA1) in three unrelated cases of congenital fiber type disproportion (CFTD) from Japan and Australia. This represents the first genetic cause of CFTD to be identified and confirms that CFTD is genetically heterogeneous. The three mutations we have identified Leucine221Proline, Aspartate292Valine, and Proline332Serine are novel. They have not been found previously in any cases of nemaline, actin, intranuclear rod, or rod-core myopathy caused by mutations in ACTA1. It remains unclear why these mutations cause type 1 fiber hypotrophy but no nemaline bodies. The three mutations all lie on one face of the actin monomer on the surface swept by tropomyosin during muscle activity, which may suggest a common pathological mechanism. All three CFTD cases with ACTA1 mutations had severe congenital weakness and respiratory failure without ophthalmoplegia. There were no clinical features specific to CFTD cases with ACTA1 mutations, but the presence of normal eye movements in a severe CFTD patient may be an important clue for the presence of a mutation in ACTA1.     

A case of chorea-acanthocytosis with dilated cardiomyopathy and myopathy]

We report a patient of chorea-acanthocytosis (CA), presenting with dilated cardiomyopathy and myopathy. The patient, 40-year-old male, was seen in our clinic because of progressive gait disturbance. Neurologically, he had chorea, tic, dystonia, diminished tendon reflexes and mild muscular atrophy and weakness. Serum creatine kinase level was elevated to 5.514 IU/l, MRI study showed atrophy of the putamen and caudate nucleus. Peripheral nerve involvement was confirmed pathologically and electrophysiologically. Acanthocytosis was found after repeated blood examinations. Furthermore, he had dilated cardiomyopathy on echocardiogram and cardiac muscle biopsy, and his muscle biopsy taken from gastrocnemius indicated myopathic changes with fiber necrosis. From these clinical and laboratory data, he was suspected to have McLeod syndrome (McS). However, he had normal expression of Kell antigens, and direct sequence of XK gene from genomic DNA sample showed no mutations. Accordingly, he was diagnosed as having CA. As CA shares the similar clinical and laboratory features with McS except Kell antigens, the evaluation of Kell blood system is crucial for differential diagnosis. As seen in our patient, blood sampling should be repeated for identification of acanthocytosis, because the finding is not always clearly present.     

Congenital muscular dystrophy of non-Fukuyama type with characteristic CT images

A 9-year-old Japanese boy with congenital muscular dystrophy (CMD) with normal intelligence was presented. He was extremely floppy and had joint contractures since birth. Motor milestones were delayed and he did not learn to walk alone. Intellectual development was normal and no convulsions were observed. On physical examination at 9 years old, he had diffuse muscle weakness and atrophy and flexion contractures of joints. Creatine kinase was normal and IQ was 95. Biopsied muscle showed myopathic changes consistent with muscular dystrophy. CT scans of the head revealed diffuse low density area in the white matter of the cerebrum. These findings suggest central nervous system involvement in CMD is not confined to Fukuyama-type CMD.     

Mitochondrial encephalomyopathy and partial cytochrome c oxidase deficiency

A 52-year-old man had slowly progressive weakness and wasting of limb-muscles, sensorineural hearing loss, and complex partial seizures. CT showed cerebral atrophy, but he was not demented. Muscle biopsy showed ragged-red fibers and decreased histochemical stain for cytochrome c oxidase. Biochemical studies showed decreased cytochrome c oxidase activity in crude muscle extracts and in isolated mitochondria (44 and 30% of normal), while other mitochondrial enzymes were normal. A comparable decrease of immunologically reactive enzyme protein was shown by immunotitration with antibodies against human heart cytochrome c oxidase. Partial defects of cytochrome c oxidase may cause adult-onset, slowly progressive mitochondrial encephalomyopathies.     

Case of eosinophilic myositis in continuum from localized nodular myositis]

We report a 72-year-old man with eosinophilic myositis (EM). At age 71 he noticed a painful nodule in his left calf. A biopsy (first biopsy) showed marked infiltration of mononucleated cells and necrotic muscle fibers. Several phagocytosed fibers were also seen. He was diagnosed as having myositis. The painful nodule disappeared spontaneously. At age 72, he again had a painful nodule, but this time in his right calf; again, this disappeared spontaneously on the first admission. Just after discharge, he noted painful nodules in the left thigh and right anterior tibial muscles and was again admitted (second admission). Neurological examination revealed mild proximal-dominant weakness in all four extremities but no other abnormalities. Laboratory studies showed elevated creatine kinase (CK) level (38,803 U/l; normal 62-287) and positive Jo-1 antibody, but no eosinophilia. Needle electromyography of the limb muscles showed myogenic patterns. Magnetic resonance imaging of the lower limbs demonstrated several T2-high and gadolinium (Gd)-enhanced lesions. Muscle biopsy (second biopsy) from the left quadriceps femoris showed marked infiltration of eosinophils; he was diagnosed as having EM. Administration of prednisolone was initiated at 60 mg/day and then gradually tapered. After starting treatment with steroids, his muscle weakness gradually ameliorated, CK level dramatically decreased, and the nodules disappeared. Clinically, the patient had developed localized nodular myositis (LNM), but pathologically it was EM without peripheral blood eosinophilia and positive Jo-1 antibody that is occasionally found in polymyositis (PM). Thus, this patient demonstrated overlapping characteristics of EM, LNM, and possibly PM, suggesting that a common mechanism underlay these conditions. As discussed, the involvement of eosinophils in three inflammatory myopathies was indicated.