The Incidence and Nature of Visual Pathway Involvement in Friedreich's Ataxia

Abstract

Pattern-reversal visual evoked potentials (VEP) were recorded from 22 patients (mean age 33.7 years) with Friedreich's ataxia, 15 of whom also had a detailed neuro-ophthalmological assessment prior to the VEP examination. None had noted symptomatic visual impairment. Eleven of the 15 (73 per cent) examined clinically had one or more neuro-ophthalmic abnormality and 14/22 (64 per cent) had an abnormal VEP study which was always binocular and comprised absent responses, or most commonly, increased P100 component latencies. The maximum P100 latency was 143 ms and the group mean was 118 ms. The P100 amplitude was also generally reduced particularly in those patients with latencies less than 115 ms (upper limit of normal), while in those with latencies above the normal range there was a significant inverse correlation between the P100 amplitude and latency. The waveform, temporal dispersion and interocular differences were normal in almost all patients with identifiable responses, including those with prolonged VEP latencies. Electroretinograms recorded from three selected patients were either normal or minimally abnormal and suggested secondary rather than primary retinal involvement. The only VEP parameter to correlate with either the duration of the generalized disease or the visual acuity was the P100 amplitude. A good correlation was found between the VEP and the clinical neuro-ophthalmic findings. Temporal pallor of the optic disc was most often associated with an abnormal VEP result and impaired visual acuity or colour vision were uncommon in the absence of VEP abnormalities. The VEP changes and those obtained from 24 age- and acuity-matched cases of demyelinating optic neuritis are contrasted and the probable pathophysiology is discussed. Two main conclusions emerge from this study. First, there is a high incidence of asymptomatic visual pathway involvement in Friedreich's ataxia which can be demonstrated by both clinical and VEP examination. Secondly, the VEP changes in Friedreich's ataxia differ from those found in typical demyelinating optic neuropathy and are consistent with progressive nerve fibre loss and associated slowing of conduction, indicating that the visual pathway is affected by the same widespread process of axonal degeneration found throughout the nervous system.

Hereditary optic neuropathies

“…Evidence of optic neuropathy is present in up to two-thirds of cases of Friedreich's ataxia, although severe visual loss is uncommon. [168][169][170][171][172][173][174] A condition resembling Friedreich's ataxia associated with decreased vitamin E levels has been localized to chromosome 8, and also includes some patients with optic atrophy. 175 Vitamin E supplementation of these patients may be efficacious early in the course of the disease.…”

Visual Involvement in Friedreich’s Ataxia: PERG and VEP Study

“…As far as optic disc pallor is concerned, Heck [11] found no optic nerve fiber atrophy while Geoffroy et al [10] observed it in 50% of their cases. More recently Carrol et al [4] have reported disc pallor in 11 out of 15 patients. In the course of the present study, we have compared traditional ophthal moscopy with red-free light retinography; our data lead us to conclude that a lack of disc pallor cannot in itself be interpreted as an absence of nerve fiber degeneration.…”

“…Electroretinal function is commonly assessed by re cording responses to flash or pattern stimuli. The few flash ERG studies carried out on a small number o f'typ ical' FA subjects have produced results variously re ported as 'normal' [21] 'subnormal' [4] or 'abnormal' [15]. These last investigators have published the only FA study using PERG [ 15], In 7 out of their 9 cases they found reduced amplitudes but normal latencies; how ever they failed to describe these changes in detail.…”

“…axon degenera tion and demyelination) have been suggested as being responsible for the abnormalities documented by visual evoked potentials (VEPs) [3,4,17,22], somatosensory evoked potentials (SEPs) [12] and auditory evoked po tentials (AEPs) [1,20] studies. While there is general agreement about the VEP changes in FA, optic atrophy has not been well defined and its reported incidence var ies in the neuro-ophthalmological and clinical literature [4,10,11], Since the impairment of visual function can be insidious and may not be subjectively perceived, sen sitive objective ophthalmological tests are needed. Redfree light retinography can detect subtle signs of retinal nerve fiber atrophy even before the appearance of disc pallor [16], Electrophysiological studies including pattern elec troretinogram (PERG) and VEP recordings provide in formation on the function of deeper retinal layers and on stimulus conduction and processing in the visual system.…”

Mitochondrial disorders and the eye

“…Frataxin is a mitochondrial protein involved in Fe-S cluster assembly, disruption of which results in excessive mitochondrial iron levels and loss of retinal ganglion cells, giving rise to optic neuropathy and ataxia. 2,4,97 The oxidative phosphorylation pathway relies on the redox ability of Fe, via multiple Fe-S clusters, to perform electron transfer and thus energy transduction. Four of the five oxidative phosphorylation complexes contain either or both heme prosthetic groups or Fe-S clusters.…”