Division of General Neurology and Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, Sao Paulo, Brazil.
Department of Neuro-Ophthalmology, National Hospital for Neurology & Neurosurgery, London, UK.
Mov Disord. 2021 Sep;36(9):2027-2035. doi: 10.1002/mds.28612. Epub 2021 Apr 23.
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) causes unique retinal abnormalities, which have not been systematically investigated.
To deeply phenotype the retina in ARSACS in order to better understand its pathogenesis and identify potential biomarkers.
We evaluated 29 patients with ARSACS, 66 with spinocerebellar ataxia (SCA), 38 with autosomal recessive cerebellar ataxia (ATX), 22 with hereditary spastic paraplegia (SPG), 21 cases of papilledema, and 20 healthy controls (total n = 196 subjects). Participants underwent visual acuity assessment, intraocular pressure measurement, fundoscopy, and macular and peripapillary optical coherence tomography (OCT). Macular layers thicknesses in ARSACS were compared with those of age-matched healthy controls. Ophthalmologists analyzed the scans for abnormal signs in the different patient groups. Linear regression analysis was conducted to look for associations between retinal changes and age, age at onset, disease duration, and Scale for the Assessment and Rating of Ataxia (SARA) scores in ARSACS.
Only patients with ARSACS exhibited peripapillary retinal striations (82%) on fundoscopy, and their OCT scans revealed foveal hypoplasia (100%), sawtooth appearance (89%), papillomacular fold (86%), and macular microcysts (18%). Average peripapillary retinal nerve fiber layer (pRNFL) was thicker in ARSACS than in SCA, ATX, SPG, and controls; a cut-off of 121 μm was 100% accurate in diagnosing ARSACS. All macular layers were thicker in ARSACS when compared to healthy controls. RNFL thickness in the inferior sector of the macula positively correlated with SARA scores.
Retinal abnormalities are highly specific for ARSACS, and suggest retinal hyperplasia due to abnormal retinal development. OCT may provide potential biomarkers for future clinical trials. © 2021 International Parkinson and Movement Disorder Society.
常染色体隐性痉挛性共济失调-沙格奈（ARSACS）引起独特的视网膜异常，但尚未对其进行系统研究。
对 ARSACS 患者的视网膜进行深入表型分析，以更好地了解其发病机制并确定潜在的生物标志物。
我们评估了 29 名 ARSACS 患者、66 名脊髓小脑性共济失调（SCA）患者、38 名常染色体隐性小脑共济失调（ATX）患者、22 名遗传性痉挛性截瘫（SPG）患者、21 例颅内压增高患者和 20 名健康对照者（共 196 名受试者）。参与者接受了视力评估、眼压测量、眼底检查和黄斑及视盘周围光学相干断层扫描（OCT）检查。将 ARSACS 患者的黄斑层厚度与年龄匹配的健康对照组进行比较。眼科医生分析了不同患者组中异常征象的扫描结果。进行线性回归分析，以寻找 ARSACS 患者视网膜变化与年龄、发病年龄、病程和共济失调评定量表（SARA）评分之间的关联。
只有 ARSACS 患者在眼底检查中出现视盘周围视网膜条纹（82%），其 OCT 扫描显示黄斑发育不良（100%）、锯齿状外观（89%）、视盘黄斑皱褶（86%）和黄斑微囊（18%）。与 SCA、ATX、SPG 和对照组相比，ARSACS 患者的视盘周围视网膜神经纤维层（pRNFL）更厚；pRNFL 厚度为 121 μm 的截断值可 100%准确诊断 ARSACS。与健康对照组相比，所有黄斑层在 ARSACS 中均较厚。黄斑下区 RNFL 厚度与 SARA 评分呈正相关。
视网膜异常对 ARSACS 具有高度特异性，提示视网膜发育异常导致视网膜过度增生。OCT 可能为未来的临床试验提供潜在的生物标志物。 © 2021 国际帕金森病和运动障碍协会。
