Disorders Affecting the Extraocular Muscles

Chronic progressive external ophthalmoplegia (CPEO) occurs in 90% of patients with mitochondrial myopathy. It is characterized by a slowly progressive ptosis and ophthalmoplegia. The ophthalmoplegia is usually preceded by ptosis for months to years, and downgaze is usually intact. Kearns-Sayre Syndrome is a subtype of chronic progressive external ophthalmoplegia. Most cases are sporadic and associated with single deletions of mitochondrial DNA. Ragged-red fibers are seen on light microscopy (using modified Gomori trichrome stain). ■ Due to accumulation of enlarged mitochondria under the sarcolemma of affected muscles ■ Found in skeletal muscles, orbicularis, and extraocular muscles ■ On electron microscopy, the mitochondria contain paracrystalline (“parking lot”) inclusions and disorganized cristae that are sometimes arranged concentrically. 1. Muscle biopsy (e.g., deltoid) 2. ERG 3. Electrocardiogram (EKG) 4. Genetic testing There is no effective treatment for CPEO. Maintaining a high-lipid, low-carbohydrate diet, taking co-enzyme Q10, biotin, or thiamine, and avoiding medications such as valproate and phenobarbital may be helpful. ■ MELAS stands for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes. ■ Maternally inherited; caused by point mutations of mitochondrial DNA (A3243G mutation accounts for about 80% of all cases) ■ Clinical features 1. Strokelike episodes before age 40 (hallmark feature) 2. Encephalopathy characterized by developmental delay, seizures, or dementia 3. Mitochondrial dysfunction manifested as lactic acidosis or ragged-red fibers 4. Ophthalmoplegia 5. Optic atrophy and pigmentary retinopathy 6. Diabetes mellitus and hearing loss ■ MNGIE stands for mitochondrial neuro-gastrointestinal encephalomyopathy. ■ Autosomal recessive; caused by mutations in the nuclear gene ECGF1, resulting in thymidine phosphorylase deficiency, which in turn causes deletions, duplications, and depletion of mitochondrial DNA ■ Clinical features: ophthalmoplegia, peripheral neuropathy, leukoencephalopathy, and gastrointestinal symptoms (recurrent nausea, vomiting, or diarrhea) with intestinal dysmotility SANDO stands for sensory ataxic neuropathy, dysarthria, and ophthalmoplegia. It is sporadic and is caused by multiple deletions of mitochondrial DNA.