Subclinical multisystem neurologic disease in 'pure' OPA1 autosomal dominant optic atrophy
| Autor: | Roger G. Whittaker, Patrick F. Chinnery, Karen M. Fisher, Mark R. Baker, Patrick Yu-Wai-Man, Philip G. Griffiths |
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| Rok vydání: | 2011 |
| Předmět: |
Pathology
medicine.medical_specialty Ataxia Mitochondrial disease DNA Mutational Analysis Neural Conduction Pyramidal Tracts Asymptomatic GTP Phosphohydrolases Optic neuropathy Atrophy Optic Atrophy Autosomal Dominant medicine Humans Myopathy Clinical/Scientific Notes Subclinical infection Electromyography business.industry Evoked Potentials Motor medicine.disease Magnetic Resonance Imaging Electric Stimulation eye diseases Mutation Optic nerve Neurology (clinical) Nervous System Diseases medicine.symptom business |
| Zdroj: | Neurology. 77:1309-1312 |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.0b013e318230a15a |
| Popis: | Mutations affecting the nuclear gene encoding the mitochondrial OPA1 protein are the commonest causes of autosomal dominant optic atrophy (DOA). More recently OPA1 mutations have been shown to cause a disorder of mitochondrial DNA (mtDNA) maintenance, thus explaining the extraocular features observed in ∼20% of OPA1 mutation carriers with “DOA+,” which include deafness, progressive external ophthalmoplegia (PEO), myopathy, ataxia, neuropathy, and spastic paraplegia.1,2 However, it remains puzzling why, unlike other hereditary mtDNA maintenance disorders (e.g., POLG1 3), most OPA1 mutation carriers only appear to develop isolated optic neuropathy. To determine whether this is actually the case, we looked for electrophysiologic evidence of subclinical multisystem disease in a sample of patients with clinically “pure” DOA. Because spasticity is an unusual clinical finding in mitochondrial disease, we were particularly interested to look for evidence of subclinical corticospinal tract (CST) disease in this clinically asymptomatic group, specifically to gain insight into the role of mitochondrial dysfunction in other more common neurodegenerative motor disorders. ### Methods. Fourteen patients with confirmed pathogenic OPA1 mutations were recruited prospectively: 1) 13 patients with bilateral optic atrophy and no evidence of any neurologic deficit, classified as “pure” DOA; and 2) 1 visually asymptomatic OPA1 mutation carrier (c.1294A>G) with no clinical or electrophysiologic evidence of optic nerve dysfunction. MRI was performed as part of the patients' initial diagnostic workup for their unexplained bilateral optic neuropathy. All patients had nerve conduction studies (NCS), needle EMG, and transcranial magnetic stimulation (TMS) was used to obtain motor evoked potentials … |
| Databáze: | OpenAIRE |
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