CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH RAGGED-RED FIBERS -CLINICAL, MORPHOLOGICAL AND GENETIC INVESTIGATIONS IN 43 PATIENTS

The evaluation of the severity of progressive external ophthalmoplegia (PEO) with ragged-red fibers in muscle, at the onset of the disease, when PEO is most often the only presenting symptom, is a difficult pro blem in neurological practice. In order to address that issue, we have performed a comparative analysis of the clinical, morphological and m olecular characteristics of 43 patients affected with that form of ocu lar myopathy. Quantification of mitochondrial accumulation was perform ed with an image analysis application on muscle sections stained with succinate dehydrogenase histochemical reaction. The proportion of musc le fibres appearing as cytochrome c oxidase deficient was used as an i ndex of the muscle-energy defect. Muscle mitochondrial DNA deletions w ere detected, localized and quantitated by Southern blot analysis. Poi nt mutations were screened in five transfer RNA genes in the mtDNA (tR NA(Leucine(UUR)),tRNA(Lysine), tRNA(Glutamine), tRNA(Isoleucine) and t RNA(Formylmethionine)) by a denaturing gradient gel electrophoresis te chnique. This investigation confirmed the high frequency of mtDNA dele tions or point mutations in PEO. At the onset of the disease, no clini cal, morphological or molecular features could predict whether PEO wou ld remain isolated or become part of a more severe multisystem disease . However, patients with mtDNA deletions were characterized by more se vere ophthalmoplegia of earlier onset. Their muscle alterations were r oughly parallel in severity to the proportion of deleted mtDNA molecul es in muscle. Patients with a multitissular disease and mtDNA deletion s were always sporadic cases and their clinical presentation was, most often, closely related to Kearns Sayre syndrome.