Journal
JOURNAL OF NEUROLOGY
Volume 267, Issue 7, Pages 2070-2082Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00415-020-09796-2
Keywords
Niemann-Pick type C; Heterozygosity; Clinical biomarker; Optical coherence tomography; Retinal neuroaxonal degeneration
Categories
Funding
- Braun Stiftung, Melsungen
- Verum Stiftung
- Else Kroner Fresenius-Stiftung
- Ara Parseghian Medical Research Fund
- German Federal Ministry of Education and Research [01ZZ1603[A-D], 01ZZ1804[A-H]]
- LMU Advanced Clinical Scientist Excellence Programme
Ask authors/readers for more resources
Objective 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. Methods 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. Results 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 (mu m):0.13 +/- 0.01 vs. 0.14 +/- 0.02; p = 0.01; GCIPL (mm(3)):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 (rho = 0.645; p < 0.05), and thinned GCIP (rho = 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 (rho = - 0.677; p < 0.01). Conclusions 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available