Abstract
BackgroundAutosomal dominant spinocerebellar ataxia type 1 is an adult onset progressive disorder with well characterized neurodegeneration in the cerebellum and brainstem. Beyond brain atrophy, few data exist concerning retinal and optic nerve involvement.Objective To evaluate retinal changes in SCA1 patients compared to age and gender matched healthy controls.Methodology/Principal FindingsNine patients with SCA1 were prospectively recruited from the ataxia clinic and were compared to nine age and gender matched healthy controls. Both cohorts received assessment of visually evoked potentials and eye examination by optical coherence tomography to determine retinal nerve fiber layer thickness and total macular volume. While no differences were found in visually evoked potentials, SCA1 patients showed a significant reduction of mean retinal nerve fiber layer thickness (RNFLT) compared to healthy controls (84±13 µm vs. 97±8 µm, p = 0.004). Temporal areas showed the most prominent RNFLT reduction with high statistical significances (temporal-inferior: p<0.001, temporal: p<0.001, temporal-superior: p = 0.005) whereas RNFLT in nasal areas was in the range of the control group. From six SCA1 patients an additional macular scan was obtained. The comparison to the corresponding healthy control showed a slight but not significant reduction in TMV (8.22±0.68 mm3 vs. 8.61±0.41 mm3, p = 0.15).ConclusionIn SCA1 patients, we found evidence for degeneration of retinal nerve fibers. The temporal focus of the observed retinal nerve fiber layer reduction suggests an involvement of the papillo-macular bundle which resembles pathology found in toxic or mitochondrial optic nerve disease such as Leber's hereditary optic neuropathy (LHON) or dominant optic atrophy (DOA).
Highlights
Spinocerebellar ataxia type 1 (SCA1) is an autosomaldominantly inherited, late-onset neurodegenerative disease primarily affecting the cerebellar cortex and brainstem
The temporal focus of the observed retinal nerve fiber layer reduction suggests an involvement of the papillo-macular bundle which resembles pathology found in toxic or mitochondrial optic nerve disease such as Leber’s hereditary optic neuropathy (LHON) or dominant optic atrophy (DOA)
Demographic parameters of the investigated cohorts and the clinical results of the SARA score, VEP, visual acuity, refractive error and the number of repeats in the polyglutamine trace of the ATXN1 alleles are summarized in table 1
Summary
Spinocerebellar ataxia type 1 (SCA1) is an autosomaldominantly inherited, late-onset neurodegenerative disease primarily affecting the cerebellar cortex and brainstem. A gain-of-function toxicity of the ataxin 1 protein was identified as the main causative agent in SCA1: In the ATXN1 gene on chromosome 6p23 a CAG-repeat expansion of variable length reaching between 39 and 83 repeats encodes for a prolonged polyglutamine chain in ataxin protein [2]. Patients with longer CAG repeat tend to have an earlier disease onset and a faster progression than patients with short repeat expansions, causing great variations in disease severity even within families [1]. Autosomal dominant spinocerebellar ataxia type 1 is an adult onset progressive disorder with well characterized neurodegeneration in the cerebellum and brainstem. Few data exist concerning retinal and optic nerve involvement
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