Is infantile spinal muscular atrophy A disease of maturation arrest or a dynamic neurogenic atrophy of the skeletal muscle?

Spinal muscular atrophy constitutes one of the major disease entities amongst infantile neuromuscular disorders. On the basis of morphological evidence, it had been suggested that the infantile spinal muscular atrophy (ISMA) is due to maturation arrest of the myofibres at 20 weeks gestation. Therefore, in the present study morphological features of skeletal muscles from patients with ISMA was compared with foetal muscle obtained at different gestational ages (9-36 weeks, n=18). Of the 35 cases of ISMA, 22 were diagnosed as having SMA-I and 13 cases an SMA-II, characterised histologically by fascicles composed of groups of small, normal, intermediate sized and hypertrophic fibres. The former ones belonged to both histochemical fibre types, while the hypertrophic fibres in 21/35 cases were type I in nature. Redundant basal lamina was a predominant finding at ultrastructural level. Mature myotubes, a feature seen during foetal muscle development was not noticed in any of the cases of ISMA. Our observations suggest denervation atrophy to be the basic pathogenic mechanism rather than arrest in maturation. This was further supported by the changes seen in the spinal cord specimen of a 20 day old infant from a case of SMA I which revealed marked fallout of motor neurons in the anterior horn, chromatolysis and gliosis. Thus ISMA is a dynamic and progressive neurogenic atrophy secondary to degeneration and loss of spinal motor neurons possibally resulting in lack of trophic factors.