Oxford University Press (OUP), Brain, 1(132), p. 116-123
DOI: 10.1093/brain/awn269
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Optic neuropathy is common in mitochondrial disorders, but poorly characterized in Friedreich's ataxia (FRDA), a recessive condition caused by lack of the mitochondrial protein frataxin. We investigated 26 molecularly confirmed FRDA patients by studying both anterior and posterior sections of the visual pathway using a new, integrated approach. This included visual field testing and optical coherence tomography (OCT), pattern visual evoked potentials (P-VEPs) and diffusion-weighted imaging. The latter was used to study optic radiation by calculating water apparent diffusion coefficients (ADC). All patients suffered optic nerve involvement with their disorder. Different patterns of visual field defects were observed and a variably reduced retinal nerve fiber layer thickness was seen by OCT in all cases. P-VEPs were abnormal in approximately half of the patients. Decreased visual acuity and temporal optic disc pallor were present in advanced stages of the disease, but only five patients were symptomatic. Two of these patients suffered a sudden loss of central vision, mimicking Leber's hereditary optic neuropathy (LHON), and of the other three symptomatic patients two were noted to be compound heterozygotes. ADC values of optic radiations in patients were significantly higher than controls (P < 0.01). Retinal nerve fiber layer thickness at OCT and P-VEPs correlated with age at onset and ICARS total score. ADC values correlated with age at onset, disease duration, GAA triplet expansion size, ICARS total score and P-VEPs. Visual pathway involvement is found consistently in FRDA, being previously underestimated, and we here document that it also involves the optic radiations. Occasional LHON-like cases may occur. However, optic neuropathy in FRDA substantially differs from classic mitochondrial optic neuropathies implying a different pathophysiology of visual system degeneration in this mitochondrial disease.