[From muscle to central nervous system: birth and future of the mitochondrial encephalomyopathy concept]

The various types of ophthalmoplegia described in the second half of the 19th century were attributed to degeneration of the oculomotor nuclei. In the middle of the 20th century, a reversal of opinions ascribed these disorders to a primary muscle lesion, and this was accepted as a dogma for 20 years. However, the finding of mitochondrial abnormalities, not only in muscles but also in the nervous system and in a variety of viscera, gradually led to the concept of a multiple system syndrome. Advances in biochemistry then revealed multiple alterations of the mitochondrial function, especially in the respiratory chain, and ultimately the concept of mitochondrial heredity was developed by molecular biology. At present, two approaches are possible. Those who opt for the first one consider that a large number of muscular, nervous, endocrine, cardiac, hepatic or renal abnormalities have as common substrate a disease of mitochondria producing unclassifiable biochemical abnormalities. Partisans of the second approach individualize, for clinical and genetic reasons, several autonomous syndromes, the best known of which is Kearns-Sayre syndrome. In any case, this evolution of concepts illustrates an advance in medicine: the starting point was a localized muscle lesion, while the end-point is a complex, multiple system dysfunction which, analyzed with increasingly greater precision, gives a glimpse of future therapeutic applications.