Ophthalmoplegia‐plus, a real nosological entity

Four patients with chronic progressive external ophthalmoplegia (c.p.e.o.), retinal, neurological, endocrine and auditory anomalies, three of whom showed signs of cardio-myopathy, are described. On biochemical examination signs of disturbed pyruvate and lactate metabolism were found and there were indications of loss of respiratory control with loosely coupling of phosphorylation (from oxidation). In the muscle biopsy specimens from all four patients aggregates of abnormal mitochondria were seen, compatible with the diagnosis of a mitochondrial myopathy. A cardiac biopsy was performed once also showing abnormalities. The great similarity in the clinical, biochemical and morphological findings justifies one comprehensive diagnosis. The term “ophthalmoplegia-plus”, although it has recently fallen into some discredit as a nosological entity, is the most obvious choice. The pathogenesis of ophthalmoplegia-plus is a widespread general disturbance of mitochondrial function, affecting various organs and systems. This distinguishes it only gradually from true ocular myopathy, and descending ocular myopathy, where only the ocular muscles and skeletal muscles, are affected by the mitochondrial anomaly (at least there is no obvious clinical involvement of other organs). Within the nosological entity of ophthalmoplegia-plus a subdivision can be made for the Kearns-Sayre syndrome, in which the clinical picture suggests that the most severe and widespread mitochondrial lesions are to be found.