Correlations between histochemical and ultrastructural studies of diseased muscle

The acceptance of a syndrome as a distinct nosological entity depends upon our ability to demonstrate that it consistent genetic, pathological and biochemical abnormalities. During the past two decades the application of enzyme histochemistry and electronmicroscopy to the study of biopsy muscle from patients from a variety of ill-defined neuromuscular disorders has enabled us to classify them with much greater precision. This approach, together with increasingly sophisticated electrophysiological techniques, has lead to a much clearer separation of neurogenic and primarily myopathic disorders with a consequent shrinkage in the category of pure muscular dystrophy. Perhaps the most useful application of morphological techniques alone has been in the field of congenital and metabolic myopathies, the histochemical and ultrastructural abnormalities in some cases providing valuable clues to the pathogenesis or even the aetiology of the underlying disease process. This applies particularly to the various glycogen storage diseases affecting skeletal muscle, disorders in which there appear to be structural and functional abnormalities of muscle mitochondria or in which excessive amounts of lipid are stored in muscle fibres. In this communication the histochemical and ultrastructural characteristics of these diseases will be detailed, their possible significance discussed and the relative non-specificity of some of these morphological abnormalities will be noted. A comment will be made on the frequency with which simple Type II fibre atrophy (as demonstrated by the myofibrillar ATPase preparation) may be accompanied by gross and bizarre ultrastructural abnormalities, e.g. in the myopathy accompanying chronic renal failure. Such inconsistencies underline the fact that it is not always possible to demonstrate a close correlation between histochemical and ultrastructural abnormalities in muscle disease. However, it should be emphasized that the combined approach is essential to the rational morphological study of these disorders.