BACKGROUND: Various inflammatory biomarkers show prognostic potential for multiple sclerosis (MS)-risk after clinically isolated syndromes. However, biomarkers are often examined singly and their interrelation and precise aspects of their associated pathological processes remain unclear. Clarification of these relationships could aid the appropriate implementation of prognostic biomarkers in clinical practice.
OBJECTIVE:To investigate the interrelation between biomarkers of inflammation, demyelination and neurodegeneration in acute optic neuritis and to assess their association to measures of MS risk.
MATERIAL AND METHODS: A prospective study at a tertiary referral centre from June 2011 to December 2012 of 56 patients with optic neuritis as a first demyelinating symptom and 27 healthy volunteers. Lumbar puncture was performed within 28 (median 16) days of onset. CSF levels of CXCL13, matrix metalloproteinase (MMP)-9, CXCL10, CCL-2, osteopontin and chitinase-3-like-1, myelin basic protein (MBP) and neurofilament light-chain (NF-L) were determined. MS-risk outcome measures were dissemination in space (DIS) of white matter lesions on cerebral MRI, CSF oligoclonal bands and elevated IgG-index.
RESULTS: Biomarkers of leukocyte infiltration (CXCL13, MMP-9 and CXCL10) were strongly associated (p<0.0001 for all). Osteopontin and chitinase-3-like-1 were also tightly associated (p<0.0001) and correlated strongly to tissue damage markers (NF-L and MBP). The biomarkers of leuvocyte infiltration all associated strongly with MS-risk parameters, whereas CHI3L1 and MBP correlated with MRI DIS, but not with CSF MS-risk parameters and osteopontin and NF-L did not correlate with any MS-risk parameters.
CONCLUSIONS:Our finding suggest two distinct inflammatry processes:
In humans it is more difficult to be precise about the timing but in optic neuritis animal studies it can be shown that there is white blood cells (leuccyte) inflammation then demyelination the nerve loss or more commonly in mice inflammation and then nerve and myelin loss. Once the nerve axon is destroyed it takes a few days for the nerve cell body in the retina of the eye to go. In optic neuritis in the mouse this can occur after brain or spinal cord lesions, with or before brain and spinal cord lesions. Therefore, it is clear that MRI and CSF studies of the brain will not absolutely correlate with the effects of optic neuritis. In this study they find that optic neuritis is associated with the presence of inflammatory markers. With time neurafilament light is found and this shows nerve damage, s humans reflect that events found in animals.