Institute of Clinical Neuroimmunology, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich, Germany.
Department of Neurology, Ludwig-Maximilians University München, Marchioninistr. 15, 81377, Munich, Germany.
J Neurol. 2020 Jul;267(7):2070-2082. doi: 10.1007/s00415-020-09796-2. Epub 2020 Mar 28.
Niemann-Pick disease type C1 (NPC1) is a rare autosomal-recessive lysosomal storage disorder presenting with a broad clinical spectrum ranging from a severe infantile-onset neurovisceral disorder to late-onset neurodegenerative disease. Optical coherence tomography (OCT) is established to detect retinal degeneration in vivo. We examined NPC1-patients (NPC1-P), clinically asymptomatic NPC1-mutation carriers (NPC1-MC), and healthy controls (HC) to (1) identify retinal degeneration in NPC1-disease and (2) to investigate possible subclinical retinal degeneration in NPC1-MC.
Fourteen NPC1-P, 17 NPC1-MC, and 31 age-matched HC were examined using spectral-domain OCT. Neurological examinations, clinical scales [modified Disability Rating Scale (mDRS); Scale for the Rating and Assessment of Ataxia (SARA); Spinocerebellar Ataxia Functional Index (SCAFI)], and video-oculography (VOG) were correlated with OCT data.
Macular retinal nerve fiber layer and volumes of combined ganglion cell and inner plexiform layer were significantly lower in NPC1-P compared to HC [mRNFL (µm):0.13 ± 0.01 vs. 0.14 ± 0.02; p = 0.01; GCIPL (mm):0.60 ± 0.05 vs. 0.62 ± 0.04; p = 0.04]. No significant differences were found in NPC1-MC in comparison to HC. In NPC1-P, the amplitude of upward vertical saccades showed positive associations with peripapillary RNFL (ρ = 0.645; p < 0.05), and thinned GCIP (ρ = 0.609; p < 0.05), but not in NPC1-MC. In NPC1-P correlations between combined outer plexiform layer and outer nuclear layer (OPONL) with mDRS (r = - 0.617; p < 0.05) and GCIP with SARA (r = - 0.622; p < 0.05) were observed. Furthermore, in NPC1-MC, motor scores were negatively associated with pRNFL (ρ = - 0.677; p < 0.01).
Using OCT, we showed retinal degeneration in NPC1-P and significant correlation between retinal neuroaxonal degeneration with clinical measurements. We observed a non-significant trend of retinal degeneration in NPC1-MC correlating with subclinical motor abnormalities. Based on these preliminary data, OCT may be an important marker of neurodegeneration in NPC1-disease after onset of clinical symptoms.
尼曼-皮克病 C1 型（NPC1）是一种罕见的常染色体隐性溶酶体贮积症，具有广泛的临床谱，从严重的婴儿发病神经内脏障碍到迟发性神经退行性疾病。光学相干断层扫描（OCT）被用于检测体内的视网膜变性。我们检查了 NPC1 患者（NPC1-P）、临床无症状 NPC1 突变携带者（NPC1-MC）和健康对照者（HC），以（1）识别 NPC1 疾病中的视网膜变性，（2）研究 NPC1-MC 中可能存在的亚临床视网膜变性。
使用谱域 OCT 检查了 14 名 NPC1-P、17 名 NPC1-MC 和 31 名年龄匹配的 HC。对神经学检查、临床量表[改良残疾评分量表（mDRS）；共济失调评定量表（SARA）；脊髓小脑共济失调功能指数（SCAFI）]和视频眼动图（VOG）与 OCT 数据进行了相关性分析。
与 HC 相比，NPC1-P 的黄斑视网膜神经纤维层和节细胞和内丛状层的容积明显降低[mRNFL（µm）：0.13±0.01 对 0.14±0.02；p=0.01；GCIPL（mm）：0.60±0.05 对 0.62±0.04；p=0.04]。与 HC 相比，NPC1-MC 无明显差异。在 NPC1-P 中，向上垂直扫视的振幅与视盘周围 RNFL（ρ=0.645；p<0.05）和变薄的 GCIP（ρ=0.609；p<0.05）呈正相关，但在 NPC1-MC 中则无相关性。在 NPC1-P 中，观察到外丛状层和外核层（OPONL）与 mDRS（r=-0.617；p<0.05）和 GCIP 与 SARA（r=-0.622；p<0.05）之间存在相关性。此外，在 NPC1-MC 中，运动评分与 pRNFL 呈负相关（ρ=-0.677；p<0.01）。
使用 OCT，我们显示 NPC1-P 存在视网膜变性，并且视网膜神经轴突变性与临床测量之间存在显著相关性。我们观察到 NPC1-MC 存在非显著性的视网膜变性趋势，与亚临床运动异常相关。基于这些初步数据，OCT 可能是 NPC1 疾病临床症状出现后神经退行性变的一个重要标志物。
