Abstract
Spinocerebellar ataxia type 1 (SCA-ATXN1) is an autosomal dominant, neurodegenerative disease, caused by CAG repeat expansion in the ataxin-1 gene (ATXN1). In isolated reports of patients with neurological signs [symptomatic patients (SP)], macular abnormalities have been described. However, no reports exist about macular anomalies in SCA1 subjects carrying the ATXN1 mutation without neurological signs [not symptomatic carriers (NSC)]. Therefore, the main aim of our work was to evaluate whether the macular functional and morphological abnormalities could be detectable in SP, genetically confirmed and with neurological signs, as well as in SCA-ATXN1-NSC, harboring pathogenic CAG expansion in ATXN1. In addition, we investigated whether the macular involvement could be associated or not to an impairment of RGCs and of their fibers and of the neural conduction along the visual pathways. Herein, nine SCA-ATXN1 subjects (6 SP and 3 NSC) underwent the following examinations: visual acuity and chromatic test assessments, fundus oculi (FO) examination, macular and peripapillary retinal nerve fiber layer thickness (RNFL-T) analysis by Spectral domain-Optical Coherence Tomography (Sd-OCT) acquisition, multifocal electroretinogram (mfERG), pattern reversal electroretinogram (PERG) and visual evoked potentials (VEP) recordings. In four eyes of two SP, visual acuity reduction and chromatic abnormalities were observed; in three of them FO changes associated with macular thinning and outer retinal defects were also detected. In three NSC eyes, slight FO abnormalities were associated with qualitative macular morphological changes. By contrast, abnormal mfERG responses (exclusively from foveal and parafoveal areas) were detected in all SP and NSC (18 eyes). No abnormalities of PERG values, RNFL-T, and VEP responses were found, but in one SP, presenting abnormal papillo-macular bundle neural conduction. Results from our SCA-ATXN1 cohort suggest that a macular dysfunction, detectable by mfERG recordings, may occur in the overt disorder, and unexpectedly in the stage of the disease in which there is still an absence of neurological signs. In NSC, an exclusive dysfunction of preganglionic macular elements can be observed, and this is associated with both normal RGCs function and neural conduction along the visual pathways.
Highlights
Autosomal dominant spinocerebellar ataxias (ADSCAs) are neurodegenerative diseases which mainly affect the cerebellum and spinal cord but may involve various other systems [1]
We acknowledge that the small number of the study cohort, which was highly selected to avoid confounding factors impacting on macular function should represent a limitation of the study
The observed remarkable data of macular dysfunction, detected in our cohort, without relevant neural conduction impairment along the visual pathways can suggest that a primary macular morpho-functional involvement in SCA1 phenotype may occur; this involvement may develop in the presence of neurological or ophthalmological signs and in their absence
Summary
Autosomal dominant spinocerebellar ataxias (ADSCAs) are neurodegenerative diseases which mainly affect the cerebellum and spinal cord but may involve various other systems [1]. The most common are the polyglutamine (polyQ) expansion spinocerebellar ataxias (SCAs), which result from a glutamine-encoding CAG repeat in the respective disease genes [2]. Spinocerebellar ataxia type 1 (SCA-ATXN1) is quite the most frequent among these rare diseases. It is caused by expanded CAG repeats (normal segments are 4–39 repeats, while the abnormal range is 40–80 repeats) in the in ataxin-1 gene (ATXN1), localized on chromosome 6p22.3 [3]. SCA-ATXN1 is characterized by an adult-onset (most frequently in the third or fourth decade) cerebellar syndrome. In the overt SCA1 disease, as in other
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