History, definition, classification, main clinical and laboratory findings, differential diagnoses of so-called floppy infant syndrome were briefly reviewed. The author discussed the problem of cerebral hypotonia with special emphasis among others illustrating three personal cases of Prader-Willi syndrome in some detail. Furthermore, the author draw special attention to the significance of the fact that selective type II fiber hypotrophy was frequently found in biopsied muscles in patients of miscellaneous central nervous system disorders with marked hypotonia.
Arthrogryposis Multiplex Congenita (A. M. C.) is a syndrome, clinically characterized by persistent joint contractures present at birth. The process may involve one or all extremities, but to varying degrees, so there may be hypotonia even when contractures are present. The authors have experienced four cases of A. M. C. By muscle biopsy and E. M. G. examinations, three of which, including bizygoid twin, were diagnosed as neurogenic A. M. C. and the other was a peculiar type in which rod bodies were observed in biopsied muscle specimens. One of the neurogenic type was died of pneumonia and the diagnosis was confirmed by autopsy. The main clinical courses and features were quite similar each other. In the first three cases, M. C. V. revealed subnormal levels and did not seem to increase with age after 3 years of age. In conclusion; first there might be neuromyogenic A.M.C. caused by certain lesions in neuromuscular system in embryonal stage. Secondly, comparing these cases with Werdnig-Hoffmann disease (W-HD), there might be neurogenic (spinal type) A. M. C. different from W-HD and con-sidering from Lebeuthal's cases, there might be myogenic A. M. C. different from congenital muscular dystrophy. Thirdly, there were evidences of pathology and electrophysiology which suggest the involvement of motor neurones in neurogenic or myogenic A. M. C.
Pathological changes of a few congenital myopathies were studied together with observations of various experimental muscular changes in animal. Pathological abnormalities of these disorders *were different in nature from those of other ordinary myopathies in that in these conditions selective type atrophy or partial structural changes within the fibers are the chief findings while in other myopathies break down of entire structure of individual fibers is indipensable change. Type I fiber atrophy was recognized in 3 cases of congenital muscular dystrophy, in each one case of myotubular myopathy and of nemaline myopathy. In nemaline myopathy, numerous nemaline bodies 2 were seen in atrophied type I fibers on a occasion, but on the other occasiona, typical neurogenic pathological picture with small groups of small fibers was observed. Central nuclei and centrally limited structural changes were characteristics of myotublar myopathy, but they were also seen, though not very frequent, in 6 cases of congenital muscular dystrophy. In myotublar myopathy, the central area of abnormal structure was varied in size, shape and in nature from to case to case. *Probably, this central variation represents various phases of a single disease process. The specific structural changes such as nemaline bodies or myotube-like structures are possibly not constant or permanent features but profiles of individual phases of certain processes. As a conclusion, it was postulated that neurogenic factors have more important role in the pathogeneses of congenital myopathies these disorders than in those of other myopathies.
The author tried to elucidate clinically the neurogenic factors in some hereditary determined myopathies, using electro-physiological, histological and neuro-endocrinological techniques. The subjects consisted of 10 cases of congenital dystrophy (Fukuyama), 7 cases of myotonic dystrophy and one case of ocular myopathy. The incidence of EEG abnormalities in congenital dystrophy is as high as 50%, which were mainly consisted of paroxysmal discharges associated with asymmetry. The quantitative histological analysis of muscle biopsy of distal and proximal portion of the same patient revealed that the distal muscle was more affected than the proximal one in 6 cases of congenital dystrophy, being in the reverse order in cases of Duchenne type progressive muscular dystrophy. Electroretinogram in myotonic dystrophy showed remarkable flat patterm. The amplitudes of a-and b-waves in both photopic and scotopic conditions were between those of primary pigmentary degeneration and normal control. Endocrinological study suggested hypersecretion of insulin in one case among 7 of myotonic dystrophy and disturbed diurnal rhythm of plasma cortisol in 3 out of 4. Gonadal dysfunction was primary. The possible mechanisms of these multisystemic involvement in myotonic dystrophy were discussed. The clinical picture of a case with ocular myopathy represented a transitional form of neuroretinal degeneration. The author classified sub-types and transitional forms of neuro-retinal dysfunctions.
Previouslywe havereported a patient, who was 17 year old male and had clinical and histological characteristics of nemaline myopathy. In this report, several clinical and histological findings of the case were represented in detail. The rod like structures which were found in the biopsied rectus femoris muscle of this patient were observed in almost all of the small and many of the medium sized fibers but rare in the large fibers. Byhistochemical examination, these rod riched fibers were revealed as type I fibers. Hitherto we have examined the biopsied muscles from about three hundred patients with various neuromuscular disorders. Out of these materials, rod like structures were found light-microsco-pically in seven cases and electronmicroscopically six cases, which consisted of various disorders such as dermatomyositis, progressive muscular dystrophy (FSH and LG types), myotonic dystrophy, toxicodermia, angitis, myasthenia gravis, diabetic neuropathy and congenital myopathies. Although rod like strucures may be found nonspecifically, congenital myopathy with both clinical and histological characteristics was as yet very rare. Therf ore, concerning to nemaline myopathy, the existence of its clinical entity as a particular congenital mvopathic disease seemso be not yet undeniable.
Two cases of central core disease and two cases of multicore disease were presented. They were noted to have slight motor retardation and their clinical courses were non progressive or very slowly progressive. Electromyography demonstrated myopathic abnormalities, however, serum enzyme levels except for one case were not increased. Histological examinations of the muscle biopsies revealed the presence of central “core” regions in most of muscle fibers in the formers. On the other hand, the biopsy findings of the latters showed multifocal myofibrillar degeneration like the core in the central core disease. Target fibers in a muscle biopsy from a patient with peripheral neuropathy were examined by light and electron microscopy. In the histochemical and electron microscopic studies, the target and the central core region were morphologically indistinguishable, and the central core region and the cores in multicore disease showed uniform appearance. The relationships of the central core disease to the multicore disease and the target fiber were discussed. The pathogenesis of the cores remains unknown.
Three cases of myotubular myopathy (8 years girl, 9 years girl and 13 years boy) were reported. Age of onset was at birth in 2 cases and 1 year after birth in one case. No heredity was found in all cases. The clinical course was progressive in 2 cases and stationary in one case. Neurological examinations revealed proximal dominant muscular weakness, decreased deep reflexes, facial muscle weakness and no sensory disturbances in all cases, abnormalities of ocular movement in 2 cases and impairment of intelligence in one case. Muscle biopsy showed centrally situated nuclei, halo around the nuclei and type I fiber atrophy which are characteristic to myotubular myopathy. Electromyographic findings were low amplitude potential, short duration and fibrillation potential. Values of serum enzymes were within normal limit. Blood chemistries were all negative. Fairly close relation was found between clinical progression and ratio of the affected fibers observed in muscle biopsy. Pathogenisis of this disease was discussed from the clinical and pathological findings.
An infant with early-onset myotonic dystrophy (MTD) born to the affected mother has been followed from the neonatal period through 19 months of life. The initial symptoms were cyanosis, difficulty in sucking and swallowing, generalized hypotonia and immobility which necessitated oxygen therapy and gevage feedings for seweral days after birth. Weakness of the facial muscle was noticed soon after birth. During the course of observation, movement of the extremities became active at 2 months. He sat at 6 months, stood with support at 11 months, but has not walked alone. Range of mobility of the hip and shoulder joints tended to increase, and the heal-to-ear sign has been constantly positive after 6 months. The muscle weakness is most prominent on the face and flexors of the anterior neck. Neither cataract, clinical and EMG myotonia of the extremities nor talipes has been detected. Though present, the patellar and Achilles tendon reflexes have been markedly depressed throughout the course. Mental development is considered as the range of debility. Biopsy of the muscle performed at 4 months showed uniformly small muscle fibers without degeneration. Few fibers showed internal nuclei.
The satellite cell, a mononucleated cell enclosed within the striated muscle fiber, has been considered to be an origin of myoblasts in the myogenesis during the fetal development or in the course of skeletal muscle regeneration. As many authors have pointed out, satellite cells increasing in number are observed in many muscle diseases including the muscular dystrophy, espescially in young children. The present paper deals with the distribution and the fine structural appearances of satellite cells in the muscles of three cases of congenital muscular dystrophy (CMD) (case 1: benign CMD, case 2: Ullrich-type CMD, case 3: Fukuyama-type CMD). In a biopsied muscle obtained from case 1, very striking features are the presence of myoblasts and of numerous satellite cells amounting to about 30% in the number of muscle fibers. These satellite cells are rich in ribosomes and endoplasmic reticulum, which suggest the presence of the activity of myoblast formation. In the muscles of cases 2 and 3, on the other hand, the satellite cells contain only a few cell organelles although they are observed in a relatively large number. The satellite cells in the muscle of case 3 show a certain degree of regressive changes along with muscle fiber degeneration. It is net fully clarified in this report, whether the presence of many satellite cells in the muscles of CMD manifests the muscle regeneration or the maturation arrest of fetal muscle.
A case of 11 year-old-boy, who has been diagnosed as Ullrich type of congenital muscular dystrophy, is presented. At 8 years of age, the diagnosis was established by the clinical picture characterized by “Akroatonien”, electromyogram, serum enzyme studies and the clinical course. After the follow-up period of three years and 6 months, he suffered from pneumonia, following which he died of severe continual insufficiency of the heart at the age of 11 years and 1 month. The autopsy was carried out and the microscopic examination revealed the distinct dystrophic changes in the skeletal muscles and slightly degenerative lesions by anoxia in the central nervous system.
An unusual case of benign congenital myopathy was presented. A boy of eight years of age has had motor retardation and difficulties in climbing stairs since the early stage of his infancy. When he was 4 years old, neurological examination revealed proximal muscular weakness, hypotonia and positive Gowers' sign. Deep tendon reflexes were all absent, and pseudohypertrophy of calf muscles were not detected. His mantality was normal. CPK level was not elevated. He was followed up by the authors during five years after the first examination. He had shown a distinct recovery course. When he was 8 years old, he was admitted to Kyushu-Koseinenkin Hospital. The principal findings on admission were as follows; 1) very mild weakness and hypotonia in extremities (proximal weakness) 2) diminished deep reflexes (not absent) 3) no fasciculations 4) slender constitution 5) no pseudohypertrophy of any muscle, no contractures of joints. Serum enzyme levels (CPK, Aldolase, GOT, GPT, LDH) was not elevated. Electromyography revealed relatively prominent low amplitude potentials with short durations as well as polyphasic units and no spontaneous discharges nor giant motor units. Muscle biopsy specimen taken from the right rectus femoris was studied with the light microscope and with the electron microscope. The diameter of the muscle fibers on the frozen sections was found to be normal. The checker board of fiber types showed normal appearance. The increase of endomysial connective tissue were unremarkable. There were no increase of subsarcolemmal nucleus and central nuscleus. In modified Gomori's trichrome staining rod-body was observed in a few muscle fibers. These inclusion bodies corresponds to the fine structure of nemaline body by the electron microscopy. And another unestablished cytoplasmic inclusion body was observed. Several cylindrical, when sectioned transversely, inclusion bodies composed of 10 to 20 concentric filaments ware accumulated in the subsarcolemmal region. There were no mitochondrial abnormalities or abnormality of glycogen granules. In some muscle fiber, focal myofibrillar degenerations were noted by electron microscopic study. Clinically, the present case is very similar to the reported cases of “Benign congenital hypotonia (Walton) ”. But there are no report of “benign congenital hypotonia (Walton) ” with a few rod-body and unusual cytoplasmic inclusions in the biopsied muscle.