Histological and histochemical changes in skeletal muscle from cases of chronic juvenile and early adult spinal muscular atrophy (the Kugelberg-Welander syndrome)

Abstract

Histological and histochemical observations have been made upon sections of skeletal muscle obtained by biopsy from juvenile and early adult cases of benign spinal muscular atrophy whose ages ranged from 4 1 2 to 42 years. Particular attention has been given to the presence of myopathic changes in surviving fascicles of muscle fibres and to the histochemical features of these fibres. Atrophic fibres were arranged in groups of varying size, contained no glycogen or RNA and had a markedly reduced content of neutral fat. Acid phosphatase activity could not be demonstrated histochemically in these fibres and SDH activity was very low. In myosin ATPase and phosphorylase preparations the atrophic fibres were usually a mixture of lightly- and deeply-staining fibres but in 1 case all stained deeply (type II fibres). Myopathic changes were found in surviving non-denervated fascicles of muscle fibres in 15 of the 17 cases of benign spinal muscular atrophy and were most marked in the older longer-standing cases. Myopathic changes were found particularly in the cases with high serum levels of creatine kinase and in those which showed myopathic features on electromyography. These changes consisted of excessive numbers of internal nuclei, hypertrophy of muscle fibres with excessive variation in fibre size, muscle fibre necrosis and regeneration, fibre-splitting and variable degrees of increase in interstitial connective tissue and fat. These changes were not found in biopsies from 9 cases of Werdnig-Hoffmann disease but were present in some cases of adult motor neurone disease and of peripheral neuropathy. The fascicles of normal-sized or hypertrophic fibres showed an abnormal degree of histochemical uniformity with, in most cases, large groups of fibres classed as type I on the basis of myosin ATPase and phosphorylase activities. However, the SDH content of these fibres was lower than that of normal type I fibres suggesting that they represent a hybrid population of fibres with histochemical characteristics of both type I and of type II fibres. In 1 case the large groups of muscle fibres were of type II with high ATPase activity. The possible explanations for the development of myopathic changes and for the transformation of the histochemical profile in surviving muscle fibres in chronically denervated muscle are considered. It is concluded that the most important factor is the reinnervation of muscle fibres by collateral sprouts from the axons of surviving motoneurones.