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. 2022 Mar 7:13:814734.
doi: 10.3389/fneur.2022.814734. eCollection 2022.

Association of Cerebrospinal Fluid Parameters and Neurofilament Light Chain With Retinal Nerve Fiber Layer Thickness in Multiple Sclerosis

Nik Krajnc  1 , Patrick Altmann  1 , Katharina Riedl  1 , Christoph Mitsch  2 , Thomas Berger  1 , Fritz Leutmezer  1 , Paulus Rommer  1 , Berthold Pemp  2 , Gabriel Bsteh  1
Affiliations

Association of Cerebrospinal Fluid Parameters and Neurofilament Light Chain With Retinal Nerve Fiber Layer Thickness in Multiple Sclerosis

Nik Krajnc et al. Front Neurol. .

Abstract

Introduction: Multiple sclerosis (MS) pathophysiology comprises both inflammatory and neurodegenerative characteristics. Cerebrospinal fluid (CSF) analysis allows for assessment of inflammation while neurofilament light chain can indicate neuroaxonal damage. Retinal thinning is a robust prognostic biomarker for neurodegeneration in MS. To date, an association between CSF parameters upon MS diagnosis and retinal thinning has not been investigated.

Aims and objectives: We aimed to determine whether CSF parameters are associated with the evolution of retinal layer thinning in people with MS (pwMS).

Methods: For this longitudinal observational study, we investigated pwMS from the Vienna MS database (VMSD), who had undergone (1) a diagnostic lumbar puncture (LP) between 2015 and 2020, and (2) simultaneous optical coherence tomography (OCT) and/or (3) a follow-up OCT scan. Linear stepwise regression models were calculated with OCT parameters (peripapillary retinal nerve fiber layer [pRNFL] thickness at LP and at follow-up, annualized loss of pRNFL thickness [aLpRNFL]) as a dependent variable, and CSF parameters (white blood cell [WBC] count, total protein [CSFTP], CSF/serum albumin ratio [Qalb], intrathecal synthesis of immunoglobulins, neurofilament light chain [NfL] in both CSF and serum [CSFNfL/sNfL]) as independent variables adjusted for age, sex, and disease duration.

Results: We analyzed 61 pwMS (median age 30.0 years [interquartile range 25.5-35.0], 57.4% female, median disease duration 1.0 month [IQR 0-2.0] before LP, median follow-up 1.9 years [IQR 1.1-3.5]). CSFNfL and sNfL measurements were available in 26 and 31 pwMS, respectively. pRNFL thickness at LP was inversely associated with the CSF WBC count (β = -0.36; 95% CI -0.51, -0.08; p = 0.008). We did not find any association between other CSF parameters, including CSFNfL, sNfL, and aLpRNFL.

Conclusions: Increased WBC count as an indicator of acute inflammation and blood-brain-barrier breakdown seems to be associated with the amount of retinal thickness already lost at the time of LP. However, neither routine CSF parameters nor a singular NfL measurement allows the prediction of future retinal thinning.

Keywords: RNFL; biomarker; cerebrospinal fluid; multiple sclerosis; neurofilament; optical coherence tomography.

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Conflict of interest statement

NK has participated in meetings sponsored by, received speaker honoraria or travel funding from Roche, Novartis, and Merck, and holds a grant for a Multiple Sclerosis Clinical Training Fellowship Programme from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). PA has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Merck, Roche, Sanofi-Genzyme, and Teva, and received honoraria for consulting from Biogen. He received a research grant from Quanterix International and was awarded a combined sponsorship from Biogen, Merck, Sanofi-Genzyme, Roche, and Teva for a clinical study. CM has received honoraria for consultancy/speaking (incl. funds for e-learning modules) from Bayer, Novartis, and Takeda. PR has received honoraria for consultancy/speaking from AbbVie, Allmiral, Alexion, Biogen, Merck, Novartis, Roche, Sandoz, Sanofi Genzyme, has received research grants from Amicus, Biogen, Merck, Roche. FL received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Alexion, Almirall, Bayer, Biogen, Celgene, MedDay, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme, Teva. TB has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Almirall, Biogen, Bionorica, Celgene/BMS, GSK, Janssen-Cilag, MedDay, Merck, Novartis, Roche, Sandoz, Sanofi-Genzyme, Teva. His institution has received financial support in the past 12 months by unrestricted research grants Biogen, Celgene/BMS, Merck, Novartis, Sanofi Aventis, Teva and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme, Teva. BP has received honoraria for consulting from Novartis. GB has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene, Lilly, Merck, Novartis, Sanofi-Genzyme, and Teva, and received honoraria for consulting Biogen, Celgene, Novartis, Sanofi-Genzyme, Roche, and Teva. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of patient selection based on the inclusion and exclusion criteria.
Figure 2
Figure 2
Cerebrospinal fluid (CSF) cell count (WBC) correlated with the peripapillary retinal nerve fiber layer (pRNFL) thickness at baseline (p = 0.008).
Figure 3
Figure 3
Baseline CSF neurofilament light chain (CSFNfL) (n = 10) and serum neurofilament light chain (sNfL) (n = 12) concentrations according to the rate of annualized loss of pRNFL (aLpRNFL).
Figure 4
Figure 4
Baseline CSFNfL (n = 23) and sNfL (n = 28) concentrations according to the pRNFL thickness at baseline. Outliers present the data outside 1.5 times the interquartile range above the upper and below the lower quartile.
See this image and copyright information in PMC

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