Analysis of the visual system in Friedreich ataxia

Seyer, Lauren; Galetta, Kristin; Wilson, James; Sakai, Reiko; Perlman, Susan; Mathews, Katherine D.; Wilmot, George; Gómez, Christopher M.; Ravina, Bernard; Zesiewicz, Theresa A.; Bushara, Khalaf; Subramony, S. H.; Ashizawa, Tetsuo; Delatycki, Martin B.; Brocht, Alicia; Balcer, Laura J.; Lynch, David R.

doi:10.1007/s00415-013-6978-z

Cited by 54 publications

(78 citation statements)

References 28 publications

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“…This is usually reflected by abnormal visually evoked potentials [3, 13]. Variable perimetric deficits, impaired contrast letter acuity, reduced retinal fiber layer thickness and optic radiation abnormalities have also been described [4, 13, 14]. …”

Section: Phenotypementioning

confidence: 99%

Friedreich Ataxia: current status and future prospects

2017

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Friedreich ataxia (FA) represents the most frequent type of inherited ataxia. Most patients carry homozygous GAA expansions in the first intron of the frataxin gene on chromosome 9. Due to epigenetic alterations, frataxin expression is significantly reduced. Frataxin is a mitochondrial protein. Its deficiency leads to mitochondrial iron overload, defective energy supply and generation of reactive oxygen species. This review gives an overview over clinical and genetic aspects of FA and discusses current concepts of frataxin biogenesis and function as well as new therapeutic strategies.

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Section: Phenotypementioning

confidence: 99%

Friedreich Ataxia: current status and future prospects

2017

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“…RNFL thinning has been demonstrated in the cerebellar subtype of multiple system atrophy (MSA-C) and spinocerebellar ataxia (SCA) types 1,2,3,6 and 7 (Pula et al, 2011, Manrique et al, 2009. In Friedreich's ataxia, RNFL thinning correlates both with markers of clinical severity and the underlying genetic process (Fortuna et al, 2009, Noval et al, 2012, Seyer et al, 2013. Thus, thinning of the peripapillary RNFL appears to be a common feature of neurodegenerative disease, even in patients with little or no evidence of visual dysfunction.…”

Section: Abbreviationsmentioning

confidence: 99%

Optical coherence tomography in autosomal recessive spastic ataxia of Charlevoix-Saguenay

Parkinson

Bartmann

Clayton

et al. 2018

Brain

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Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a rare neurodegenerative disorder caused by mutations in the SACS gene. Thickened retinal nerve fibres visible on fundoscopy have previously been described in these patients; however, thickening of the retinal nerve fibre layer as demonstrated by optical coherence tomography appears to be a more sensitive and specific feature. To test this observation, we assessed 292 individuals (191 patients with ataxia and 101 control subjects) by peripapillary time-domain optical coherence tomography. The patients included 146 with a genetic diagnosis of ataxia (17 autosomal spastic ataxia of Charlevoix-Saguenay, 59 Friedreich's ataxia, 53 spinocerebellar ataxias, 17 other genetically confirmed ataxias) and 45 with cerebellar ataxia of unknown cause. The controls included 13 asymptomatic heterozygotes for SACS mutations and 88 unaffected controls. The cases with autosomal recessive spastic ataxia of Charlevoix-Saguenay included 11 previously unpublished SACS mutations, of which seven were nonsense and four missense mutations. Most patients were visually asymptomatic and had no previous history of ophthalmic complaints and normal or near normal visual test results. None had visual symptoms directly attributable to the retinal changes. Twelve of the 17 cases (70.6%) had thickened retinal nerve fibres visible on fundoscopy. All patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay had thickening of the peripapillary retinal nerve fibre layer on optical coherence tomography, whereas all the remaining cases and controls except one showed normal or reduced average peripapillary retinal nerve fibre layer thickness on optical coherence tomography. We propose a cut-off value of 119 µm in average peripapillary retinal nerve fibre layer thickness, which provides a sensitivity of 100% and specificity of 99.4% amongst patients affected with ataxia. This is the largest cohort of patients with this condition to undergo systematic evaluation by optical coherence tomography. This is a useful tool in identifying cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay from other causes of ataxia. Visualization of thickened retinal fibres by direct fundoscopy is less sensitive. We therefore advocate the use of this technique in the assessment of possible cases of this condition.

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“…Next we explored the visual system, because in FRDA patients, various visual field defects have been reported, suggesting that photoreceptors and the retinal pigment epithelium (RPE) can be affected 41,42 . By electron microscopic examination of the photoreceptors in the retina, which are specialized neurons capable of phototransduction, we observed disruption in Tg + mice at 20 weeks (Online Methods; Fig.…”

Section: Frataxin Knockdown Causes Neuronal Degenerationmentioning

confidence: 99%