Background

Optical coherence tomography is gaining increasing relevance in the assessment of people with multiple sclerosis. Converging evidence point to the view that neuro-retinal changes, in eyes without acute optic neuritis, reflect inflammatory and neurodegenerative processes taking place throughout the CNS.

Objectives

The present study aims at exploring the usefulness of optical coherence tomography as a marker of inflammation and disease burden in the earliest phases of the disease.

Methods

a cohort of 150 consecutive patients underwent clinical, neurophysiological and brain MRI assessment as well as lumbar puncture as part of their diagnostic workup for a neurological episode suggestive of inflammatory CNS disorder. For the present study, patients also received a visual pathway assessment - including OCT, VEP, visual acuity testing –, measurement of CSF inflammatory markers – a set of 17 cytokines-chemokines and, count of extracellular vesicles of myeloid origin –, and dosage of serum neurofilaments.

Results

19.2% of clinically isolated syndromes had abnormal visual evoked potentials in eyes without optic neuritis. Similarly, optical coherence tomography identified neuro-retinal thinning in 17.8% of patients without prior visual symptoms. The presence of asymptomatic involvement of the anterior optic pathway tested with either techniques was associated with a greater disease burden.

A thinner ganglion cell layer in eyes without prior optic neuritis or instrumental evidences of it was correlated with higher EDSS, lower low contrast visual acuity, longer disease duration, higher brain lesion load, presence of gadolinium enhancing lesions, more severe abnormalities along motor and somatosensory evoked potentials, and higher frequency of CSF-specific oligoclonal bands.

We also found that inner nuclear layer thickens in a post-acute (1.1 – 3.7 months) phase after a relapse, particularly in those who did not receive steroid treatment. Likewise, a longitudinal analysis on 65 patients, showed that this swelling is transient and returns to normal values after one year of follow-up. Notwithstanding, the clinical, MRI, serological and CSF markers of disease activity considered in the study were strictly associated with one-another but none of them was associated with inner nuclear layer volume.

Conclusions

The present findings suggest that instrumental evidence of asymptomatic optic nerve involvement is associated with a greater disease burden in early MS and clinically isolated syndrome. Neuro-retinal changes are present since the earliest phases of the disease and yield important information regarding the neurodegenerative and inflammatory processes occurring in the CNS.

Background

Optic neuritis is an immune-mediated disease of the optic nerve, strongly associated with multiple sclerosis (MS). Although the visual prognosis of optic neuritis is generally favourable, the degree of remission varies considerably. The degree of clinical remission is associated with the degree of optic nerve axonal loss, that can be quantified accurately by Optic Coeherence Tomography (OCT). Neurofilament light chain (NfL) is part of the axonal cytoskeletal neurofilaments and is released upon immune-mediated axonal damage during optic neuritis and MS.

Objectives

We aimed to investigate if NfL levels sampled close after symptom onset would predict the outcome after optic neuritis.

Methods

We included 31 patients with optic neuritis as a first demyelinating episode. Patients underwent visual tests, OCT, magnetic resonance imaging (MRI) and lumbar puncture. NfL levels were measured through use of a Simoa HD-1 instrument (Quanterix). Longitudinal changes in inter-ocular difference in visual acuity and OCT parameters were chosen as primary outcome measures of visual loss to account for their inter-individual variability. Multilevel mixed effect models have been used to assess the prognostic factor of baseline NfL levels on longitudinal changes in visual outcomes.

Results

Results: patients (mean age 37.3 years, SD 8.7, 71% females) had a mean follow-up of 27.6 months (SD 12.3). The mean inter-ocular visual acuity difference decreased with the follow-up (baseline 2.8 SD 1.2, follow up 2.1 SD 1.5, p <0.05), while mean inter-ocular RNFL thickness difference significantly increased with time (3.2 SD 10.2 at baseline, 12.7 SD 15.2 at follow-up). Basel NfL levels above 75°ile were significantly associated with an increase in inter-ocular visual acuity difference (B 0.05 SE 0.02, p <0.01) and inter-ocular RNFL thickness difference (B 0.64 SE 0.20, p <0.01).

Conclusions

Conclusion: NfL is a promising biomarker of visual outcome after optic neuritis. This could aid neuroprotective/regenerative medical advancements.

Abstract

Neurofilaments: towards application in clinical practice

1. Do neurofilaments predict MS disease course?

Mark Freedman

3. Quantifying therapy response in MS by neurofilaments?

Jens Kuhle

3. Neurofilament applications outside the MS field

Roberto Furlan

Abstract

Neurofilaments are in late stage development as biomarkers for numerous neurological disorders, including MS. Their interpretation, their diagnostic, prognostic, monitoring value have to be established empirically but also through the understanding of their biology, mechanisms of release, kinetic. Data taken from several different diseases and experimental settings, including Alzheimer’s Disease, Parkinson’s Disease, amyotrophic lateral sclerosis, peripheral neuropathies, stroke, experimental cardiac arrest, bipolar disorder, and even COVID-19 will be discussed in order to assess potentialities, limits, confounding factors, perspectives of a biomarker that has raised huge interests and re-ignited the field of biological fluid biomarkers in neurology, but might require still more in depth knowledge to be correctly used and interpreted.

Abstract

Neurofilaments are in late stage development as biomarkers for numerous neurological disorders, including MS. Their interpretation, their diagnostic, prognostic, monitoring value have to be established empirically but also through the understanding of their biology, mechanisms of release, kinetic. Data taken from several different diseases and experimental settings, including Alzheimer’s Disease, Parkinson’s Disease, amyotrophic lateral sclerosis, peripheral neuropathies, stroke, experimental cardiac arrest, bipolar disorder, and even COVID-19 will be discussed in order to assess potentialities, limits, confounding factors, perspectives of a biomarker that has raised huge interests and re-ignited the field of biological fluid biomarkers in neurology, but might require still more in depth knowledge to be correctly used and interpreted.

Abstract

Neurofilaments are in late stage development as biomarkers for numerous neurological disorders, including MS. Their interpretation, their diagnostic, prognostic, monitoring value have to be established empirically but also through the understanding of their biology, mechanisms of release, kinetic. Data taken from several different diseases and experimental settings, including Alzheimer’s Disease, Parkinson’s Disease, amyotrophic lateral sclerosis, peripheral neuropathies, stroke, experimental cardiac arrest, bipolar disorder, and even COVID-19 will be discussed in order to assess potentialities, limits, confounding factors, perspectives of a biomarker that has raised huge interests and re-ignited the field of biological fluid biomarkers in neurology, but might require still more in depth knowledge to be correctly used and interpreted.