Serum neurofilament levels correlate with retinal nerve fiber layer thinning in multiple sclerosis

Background: Serum neurofilament light chain (sNfL) and distinct intra-retinal layers are both promising biomarkers of neuro-axonal injury in multiple sclerosis (MS). We aimed to unravel the association of both markers in early MS, having identified that neurofilament has a distinct immunohistochemical expression pattern among intra-retinal layers. Methods: Three-dimensional (3D) spectral domain macular optical coherence tomography scans and sNfL levels were investigated in 156 early MS patients (female/male: 109/47, mean age: 33.3 ± 9.5 years, mean disease duration: 2.0 ± 3.3 years). Out of the whole cohort, 110 patients had no history of optic neuritis (NHON) and 46 patients had a previous history of optic neuritis (HON). In addition, a subgroup of patients ( n = 38) was studied longitudinally over 2 years. Support vector machine analysis was applied to test a regression model for significant changes. Results: In our cohort, HON patients had a thinner outer plexiform layer (OPL) volume compared to NHON patients ( B = −0.016, SE = 0.006, p = 0.013). Higher sNfL levels were significantly associated with thinner OPL volumes in HON patients ( B = −6.734, SE = 2.514, p = 0.011). This finding was corroborated in the longitudinal subanalysis by the association of higher sNfL levels with OPL atrophy ( B = 5.974, SE = 2.420, p = 0.019). sNfL levels were 75.7% accurate at predicting OPL volume in the supervised machine learning. Conclusions: In summary, sNfL levels were a good predictor of future outer retinal thinning in MS. Changes within the neurofilament-rich OPL could be considered as an additional retinal marker linked to MS neurodegeneration.

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“… 31 In fact, sNfL has been shown to correlate with atrophy of the pRNFL. 32 …”

Section: Discussionmentioning

confidence: 99%

Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis

Seitz

Steffen

Uphaus

et al. 2021

Ther Adv Neurol Disord

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“…Elevated serum NfL levels are also associated with retinal nerve fiber thinning in patients with multiple sclerosis. 46 NfL has been suggested as a biomarker of neuro-axonal damage. 46 It seems promising that serum NfL levels could be used to identify infants at risk of developing ROP.…”

Section: Rop Nfl and The Retinamentioning

confidence: 99%

Analysis of Brain Injury Biomarker Neurofilament Light and Neurodevelopmental Outcomes and Retinopathy of Prematurity Among Preterm Infants

et al. 2021

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Key Points Question How do serum levels of the brain injury biomarkers neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) change after preterm birth, and are these biomarkers associated with neonatal morbidities? Findings In this cohort study of 221 infants born preterm, infants experienced a postnatal increase in NfL that continued for at least 1 month after birth. High serum levels of NfL were associated with the retinal neurovascular disease retinopathy of prematurity (ROP) and, in an exploratory analysis, associated with an unfavorable neurodevelopmental outcome at 2 years of age. Meaning These findings suggest that serum levels of the neuronal injury biomarker NfL might be used as an early clinical biomarker of ROP development and neurodevelopmental outcome; however, this should be investigated further.

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“…(MS) first, where concentrations of serum neurofilament light chains (sNfL) have shaped into a piece in the puzzle that is monitoring of disease and prediction of outcome or therapeutic response [8][9][10] .…”

mentioning

confidence: 99%

Serum neurofilament light chain withstands delayed freezing and repeated thawing

Altmann

Leutmezer

Zach

et al. 2020

Sci Rep

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Serum neurofilament light chain (sNfL) and its ability to expose axonal damage in neurologic disorders have solicited a considerable amount of attention in blood biomarker research. Hence, with the proliferation of high-throughput assay technology, there is an imminent need to study the pre-analytical stability of this biomarker. We recruited 20 patients with common neurological diagnoses and 10 controls (i.e. patients without structural neurological disease). We investigated whether a variation in pre-analytical variables (delayed freezing up to 24 h and repeated thawing/freezing for up to three cycles) affects the measured sNfL concentrations using state of the art Simoa technology. Advanced statistical methods were applied to expose any relevant changes in sNfL concentration due to different storing and processing conditions. We found that sNfL concentrations remained stable when samples were frozen within 24 h (mean absolute difference 0.2 pg/ml; intraindividual variation below 0.1%). Repeated thawing and re-freezing up to three times did not change measured sNfL concentration significantly, either (mean absolute difference 0.7 pg/ml; intraindividual variation below 0.2%). We conclude that the soluble sNfL concentration is unaffected at 4–8 °C when samples are frozen within 24 h and single aliquots can be used up to three times. These observations should be considered for planning future studies.

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Serum neurofilament levels correlate with retinal nerve fiber layer thinning in multiple sclerosis

Cited by 29 publications

References 24 publications

Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis

Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis

Analysis of Brain Injury Biomarker Neurofilament Light and Neurodevelopmental Outcomes and Retinopathy of Prematurity Among Preterm Infants

Serum neurofilament light chain withstands delayed freezing and repeated thawing

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