Contributions
Abstract: P543
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Optic neuritis (ON) is an inflammatory optic neuropathy causing demyelination and axonal injury. The relation between intrathecal markers of inflammation and markers of neurodegeneration in acute ON is incompletely understood.
Objective: To investigate neurofilament light-chain (NF-L) and inflammatory biomarkers in the cerebrospinal fluid (CSF) in patients with acute ON and their potential to predict a diagnosis of multiple sclerosis (MS).
Methods and patients: We recruited 40 patients with acute isolated ON (ION) in a population-based prospective cohort with a one-year follow-up. Paired serum and CSF samples were taken prior to glucocorticoid treatment with a median interval from onset of symptoms of 14 days (range 2-38). Overall, 12/40 patients were diagnosed with MS at onset of ON and additionally 4 were diagnosed at follow-up; 24 patients remained as ION. IL-1β, IL-6, IL-10, IL-17A, TNF-α (serum and CSF) and NF-L (CSF only) were measured by digital ELISA on the Simoa platform; CXCL13 in CSF was measured by ELISA (Euroimmun). Comparisons were made using Kruskal-Wallis test followed by the Benjamini-Hochberg FDR method.
Results: TNF-α, IL-10 and CXCL13 levels in CSF were significantly increased in MS-ON compared to ION patients (p-values: 0.006, 0.010 and 0.03, respectively). MS-ON patients had more CSF leukocytes than ION (p=0.0018) as well as more CSF-restricted oligoclonal bands (p=0.015). Levels of IL-10, TNF-α, IL-17A and CXCL13 in CSF were all significantly correlated with leukocyte counts (r>0.69 and p< 0.002 for all). In MS-ON, but not in ION patients, a time-dependent increase in CSF NF-L levels was observed in the period between 7 to 14 days after disease onset (r=0.73, p< 0.0065). We detected no significant correlation between NF-L and markers of inflammation.
Conclusions: CSF levels of NF-L and inflammatory markers were associated with the development of MS at an early time point in acute ON, suggesting that the inflammatory and neurodegenerativeprocesses of MS occur already at the first demyelinating event.
Disclosure: MN Olesen: Received travel support from Merck
K Soelberg: Received travel support from Merck
AC Nilsson: Nothing to disclose
S Jarius: Nothing to disclose
JS Madsen: Nothing to disclose
J Grauslund: Nothing to disclose
TJ Smith: Holds patents on the therapeutic targeting of the insulin-like growth factor I receptor and the clinical assay development of anti-IGF-IR antibodies in autoimmune diseases. Funded by National Institutes of Health grants EY008976 and 5UM1AI110557, Center for Vision core grant EY007003 from the National Eye Institute, unrestricted grants from Research to Prevent Blindness and the Bell Charitable Foundation
ST Lillevang: Nothing to disclose
I Brandslund: Nothing to disclose
F Paul: Serves on the scientific advisory board for Novartis; received speaker honoraria and travel funding from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Merck, Serono, Alexion, Chugai, MedImmune, and Shire; is an academic editor for PLoS ONE; is an associate editor for Neurology® Neuroimmunology & Neuroinflammation; consulted for SanofiGenzyme, Biogen Idec, MedImmune, Shire, and Alexion; and received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation
Berlin, Guthy Jackson Charitable Foundation, and National Multiple Sclerosis of the USA.
N Asgari: Received travel support from Merck
Abstract: P543
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Optic neuritis (ON) is an inflammatory optic neuropathy causing demyelination and axonal injury. The relation between intrathecal markers of inflammation and markers of neurodegeneration in acute ON is incompletely understood.
Objective: To investigate neurofilament light-chain (NF-L) and inflammatory biomarkers in the cerebrospinal fluid (CSF) in patients with acute ON and their potential to predict a diagnosis of multiple sclerosis (MS).
Methods and patients: We recruited 40 patients with acute isolated ON (ION) in a population-based prospective cohort with a one-year follow-up. Paired serum and CSF samples were taken prior to glucocorticoid treatment with a median interval from onset of symptoms of 14 days (range 2-38). Overall, 12/40 patients were diagnosed with MS at onset of ON and additionally 4 were diagnosed at follow-up; 24 patients remained as ION. IL-1β, IL-6, IL-10, IL-17A, TNF-α (serum and CSF) and NF-L (CSF only) were measured by digital ELISA on the Simoa platform; CXCL13 in CSF was measured by ELISA (Euroimmun). Comparisons were made using Kruskal-Wallis test followed by the Benjamini-Hochberg FDR method.
Results: TNF-α, IL-10 and CXCL13 levels in CSF were significantly increased in MS-ON compared to ION patients (p-values: 0.006, 0.010 and 0.03, respectively). MS-ON patients had more CSF leukocytes than ION (p=0.0018) as well as more CSF-restricted oligoclonal bands (p=0.015). Levels of IL-10, TNF-α, IL-17A and CXCL13 in CSF were all significantly correlated with leukocyte counts (r>0.69 and p< 0.002 for all). In MS-ON, but not in ION patients, a time-dependent increase in CSF NF-L levels was observed in the period between 7 to 14 days after disease onset (r=0.73, p< 0.0065). We detected no significant correlation between NF-L and markers of inflammation.
Conclusions: CSF levels of NF-L and inflammatory markers were associated with the development of MS at an early time point in acute ON, suggesting that the inflammatory and neurodegenerativeprocesses of MS occur already at the first demyelinating event.
Disclosure: MN Olesen: Received travel support from Merck
K Soelberg: Received travel support from Merck
AC Nilsson: Nothing to disclose
S Jarius: Nothing to disclose
JS Madsen: Nothing to disclose
J Grauslund: Nothing to disclose
TJ Smith: Holds patents on the therapeutic targeting of the insulin-like growth factor I receptor and the clinical assay development of anti-IGF-IR antibodies in autoimmune diseases. Funded by National Institutes of Health grants EY008976 and 5UM1AI110557, Center for Vision core grant EY007003 from the National Eye Institute, unrestricted grants from Research to Prevent Blindness and the Bell Charitable Foundation
ST Lillevang: Nothing to disclose
I Brandslund: Nothing to disclose
F Paul: Serves on the scientific advisory board for Novartis; received speaker honoraria and travel funding from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Merck, Serono, Alexion, Chugai, MedImmune, and Shire; is an academic editor for PLoS ONE; is an associate editor for Neurology® Neuroimmunology & Neuroinflammation; consulted for SanofiGenzyme, Biogen Idec, MedImmune, Shire, and Alexion; and received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation
Berlin, Guthy Jackson Charitable Foundation, and National Multiple Sclerosis of the USA.
N Asgari: Received travel support from Merck