TY - JOUR

T1 - Cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis

AU - Modvig, S

AU - Degn, M

AU - Roed, H

AU - Sørensen, Torben Lykke

AU - Larsson, Hbw

AU - Langkilde, Ar

AU - Fredriksen, Jette Lautrup

AU - Sellebjerg, F

N1 - © The Author(s), 2015.

PY - 2015/12

Y1 - 2015/12

N2 - BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been suggested to predict multiple sclerosis (MS) after clinically isolated syndromes, but studies investigating long-term prognosis are needed.OBJECTIVE: To assess the predictive ability of CSF biomarkers with regard to MS development and long-term disability after optic neuritis (ON).METHODS: Eighty-six patients with ON as a first demyelinating event were included retrospectively. Magnetic resonance imaging (MRI), CSF leukocytes, immunoglobulin G index and oligoclonal bands were registered. CSF levels of chitinase-3-like-1, osteopontin, neurofilament light-chain, myelin basic protein, CCL2, CXCL10, CXCL13 and matrix metalloproteinase-9 were measured by enzyme-linked immunosorbent assay. Patients were followed up after 13.6 (range 9.6-19.4) years and 81.4% were examined, including Expanded Disability Status Scale and MS functional composite evaluation. 18.6% were interviewed by phone. Cox regression, multiple regression and Spearman correlation analyses were used.RESULTS: Forty-six (53.5%) developed clinically definite MS (CDMS) during follow-up. In a multivariate model MRI (p=0.0001), chitinase 3-like 1 (p=0.0033) and age (p=0.0194) combined predicted CDMS best. Neurofilament light-chain predicted long-term disability by the multiple sclerosis severity scale (p=0.0111) and nine-hole-peg-test (p=0.0202). Chitinase-3-like-1 predicted long-term cognitive impairment by the paced auditory serial addition test (p=0.0150).CONCLUSION: Neurofilament light-chain and chitinase-3-like-1 were significant predictors of long-term physical and cognitive disability. Furthermore, chitinase-3-like-1 predicted CDMS development. Thus, these molecules hold promise as clinically valuable biomarkers after ON as a first demyelinating event.

AB - BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been suggested to predict multiple sclerosis (MS) after clinically isolated syndromes, but studies investigating long-term prognosis are needed.OBJECTIVE: To assess the predictive ability of CSF biomarkers with regard to MS development and long-term disability after optic neuritis (ON).METHODS: Eighty-six patients with ON as a first demyelinating event were included retrospectively. Magnetic resonance imaging (MRI), CSF leukocytes, immunoglobulin G index and oligoclonal bands were registered. CSF levels of chitinase-3-like-1, osteopontin, neurofilament light-chain, myelin basic protein, CCL2, CXCL10, CXCL13 and matrix metalloproteinase-9 were measured by enzyme-linked immunosorbent assay. Patients were followed up after 13.6 (range 9.6-19.4) years and 81.4% were examined, including Expanded Disability Status Scale and MS functional composite evaluation. 18.6% were interviewed by phone. Cox regression, multiple regression and Spearman correlation analyses were used.RESULTS: Forty-six (53.5%) developed clinically definite MS (CDMS) during follow-up. In a multivariate model MRI (p=0.0001), chitinase 3-like 1 (p=0.0033) and age (p=0.0194) combined predicted CDMS best. Neurofilament light-chain predicted long-term disability by the multiple sclerosis severity scale (p=0.0111) and nine-hole-peg-test (p=0.0202). Chitinase-3-like-1 predicted long-term cognitive impairment by the paced auditory serial addition test (p=0.0150).CONCLUSION: Neurofilament light-chain and chitinase-3-like-1 were significant predictors of long-term physical and cognitive disability. Furthermore, chitinase-3-like-1 predicted CDMS development. Thus, these molecules hold promise as clinically valuable biomarkers after ON as a first demyelinating event.

U2 - 10.1177/1352458515574148

DO - 10.1177/1352458515574148

M3 - Journal article

C2 - 25698172

VL - 21

SP - 1761

EP - 1770

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

SN - 1352-4585

IS - 14

ER -