Functionally Relevant Maculopathy and Optic Atrophy in Spinocerebellar Ataxia Type 1

Oertel, Frederike Cosima; Zeitz, Oliver; Rönnefarth, Maria; Bereuter, Charlotte; Motamedi, Seyedamirhosein; Zimmermann, Hanna; Kuchling, Joseph; Grosch, Anne Sophie; Doss, Sarah; Browne, Andrew; Paul, Friedemann; Schmitz‐Hübsch, Tanja; Brandt, Alexander U.

doi:10.1002/mdc3.12949

Cited by 8 publications

(18 citation statements)

References 35 publications

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“…The suggested correlation of the cerebellum volume and the GCL-IPL complex thickness may be related to the structural similarities in both areas, that includes spatial organizations, and molecular expressions of regulatory factors, although our findings did not reach statistical significance [81,82]. The association of retinal dysfunction to cerebellar ataxias is well documented [83][84][85][86][87]. The nature of the exact mechanism for the retinal involvement in the ataxias may be multifactorial, based on the exact pathophysiology of each entity, but an underling parallel relationship of the two structures is likely part of the explanation and the present correlation.…”

Section: Discussioncontrasting

confidence: 55%

OCT parameters of the optic nerve head and the retina as surrogate markers of brain volume in a normal population, a pilot study

Mejia-Vergara

Karanjia

Sadun

2021

Journal of the Neurological Sciences

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The relationship between optical coherence tomography (OCT) measurements of the retinal structures has been described for various neurological diseases including Multiple Sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). Brain volume changes, both globally and by area, are associated with some of these same diseases, yet the correlation of OCT and disease is not fully elucidated.Our study looked at normal subjects, at the correlation of OCT measurements and brain volumes, both globally and for specific regions including the pericalcarine grey matter, entorhinal grey matter, and cerebellar volume using a retrospective, cross-sectional cohort study design.Thickness of the retinal nerve fiber layer (RNFL) as measured by OCT, correlated with volume of the pericalcarine grey matter, when adjusted for age and gender. Similarly, thickness of the ganglion cell layer-inner plexiform layer complex may be associated with both entorhinal grey matter volumes and total cerebellar volumes, although our pilot study did not reach statistical significance. This suggests that both eye and brain volumes follow a similar trajectory and understanding the inter-relationship of these structures will aid in the analysis of changes seen in disease. Further studies are needed to longitudinally demonstrate these relationships.

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Section: Discussioncontrasting

confidence: 55%

OCT parameters of the optic nerve head and the retina as surrogate markers of brain volume in a normal population, a pilot study

Mejia-Vergara

Karanjia

Sadun

2021

Journal of the Neurological Sciences

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“…Previous studies performed in visually impaired SCA-AXN1 patients [12,13], reported macular dysfunction assessed by mfERG recording [10,12], as well as macular morphological abnormalities detected by Sd-OCT examination. About the RGCs function, in absence of PERG results in SCA-ATXN1 patients, it seems that this matter was never investigated in this disease; regarding the RGC axon morphology, contrasting evidence has been reported, describing either reduced [13,17] or normal RNFL-T values [15].…”

Section: Introductionmentioning

confidence: 94%

“…In the overt SCA1 disease, as in other ADSCAs [6][7][8], relevant ocular impairment inducing a decrease in visual function has been reported. In details, macular dystrophy, outer retinal cavitation or foveal photoreceptoral disruption [9][10][11][12][13][14], as well as eye movement abnormalities or visual pathways disorders, as optic atrophy [13,[15][16][17], have been described in patients with neurological signs (SP).…”

Section: Introductionmentioning

confidence: 99%

Macular Morpho-Functional and Visual Pathways Functional Assessment in Patients with Spinocerebellar Type 1 Ataxia with or without Neurological Signs

Ziccardi

Cioffi

Barbano

et al. 2021

JCM

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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.

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“…They also asserted that OCT and multifocal ERG could help to reliably detect these macular pathology associated with SCA1 ( Nishiguchi et al, 2019 ). Color vision abnormalities may present in some SCA1 patients with photoreceptor ellipsoid zone disruption ( Oertel et al, 2020 ).…”

Section: Spinocerebellar Ataxia Typementioning

confidence: 99%

“…A recent case series by Nishiguchi et al reported temporal RNFL thinning ( Nishiguchi et al, 2019 ). Oertel et al has reported that peripapillary retinal nerve fiber layer thickness and combined ganglion cell and inner plexiform layer volume as markers of optic atrophy measured by OCT were reduced in 20 patients with SCA1 compared with healthy controls ( Oertel et al, 2020 ).…”

Section: Spinocerebellar Ataxia Typementioning

confidence: 99%

Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review

2020

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Spinocerebellar ataxia (SCA) is a part of the cerebellar neurodegenerative disease group that is diverse in genetics and phenotypes. It usually shows autosomal dominant inheritance. SCAs, always together with the cerebellar degeneration, may exhibit clinical deficits in brainstem or eye, especially retina or optic nerve. Interestingly, autosomal dominant SCAs share a common genetic mechanism; the length of the glutamine chain is abnormally expanded due to the increase in the cytosine-adenine-guanine (CAG) repeats of the disease causing gene. Studies have suggested that the mutant ataxin induces alteration of protein conformation and abnormal aggregation resulting in nuclear inclusions, and causes cellular loss of photoreceptors through a toxic effect. As a result, these pathologic changes induce a downregulation of genes involved in the phototransduction, development, and differentiation of photoreceptors such as CRX, one of the photoreceptor transcription factors. However, the exact mechanism of neuronal degeneration by mutant ataxin restricted to only certain type of neuronal cell including cerebellar Purkinje neurons and photoreceptor is still unclear. The most common SCAs are types 1, 2, 3, 6, 7, and 17 which contain about 80% of autosomal dominant SCA cases. Various aspects of eye movement abnormalities are evident depending on the degree of cerebellar and brainstem degeneration in SCAs. In addition, certain types of SCAs such as SCA7 are characterized by both cerebellar ataxia and visual loss mainly due to retinal degeneration. The severity of the retinopathy can vary from occult macular photoreceptor disruption to extensive retinal atrophy and is correlated with the number of CAG repeats. The value of using optical coherence tomography in conjunction with electrodiagnostic and genetic testing is emphasized as the combination of these tests can provide critical information regarding the etiology, morphological evaluation, and functional significances. Therefore, ophthalmologists need to recognize and differentiate SCAs in order to properly diagnose and evaluate the disease. In this review, we have described and discussed SCAs showing ophthalmic abnormalities with particular attention to their ophthalmic features, neurodegenerative mechanisms, genetics, and future perspectives.

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Functionally Relevant Maculopathy and Optic Atrophy in Spinocerebellar Ataxia Type 1

Cited by 8 publications

References 35 publications

OCT parameters of the optic nerve head and the retina as surrogate markers of brain volume in a normal population, a pilot study

OCT parameters of the optic nerve head and the retina as surrogate markers of brain volume in a normal population, a pilot study

Macular Morpho-Functional and Visual Pathways Functional Assessment in Patients with Spinocerebellar Type 1 Ataxia with or without Neurological Signs

Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review

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