Contributions
Abstract: P625
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Introduction: Biomarkers of disease activity that have reliable prognostic utility in MS are lacking.
The aim of this study was to determine whether the level of neurofilament light chain (NFL) in the cerebrospinal fluid (CSF) of MS patients, correlates with disease activity and progression.
Methods: Between June 2015 and April 2016 we analyzed all available CSF samples from patients with clinically isolated syndrome (CIS) or MS, collected up to August 2014 and stored at Verona University Hospital. Clinical and MRI variables were obtained retrospectively from medical records. CSF standard examination and isoelectrofocusing for oligoclonal bands were performed at Verona University Hospital at the time of diagnostic lumbar puncture. NFL concentration was assessed using a commercially available ELISA kit.
Results: Of the 111 analyzed CSF samples, 25 were collected from CIS and 86 from MS patients
(72 with relapsing-remitting and 14 with progressive course). We observed a significant increase in CSF NFL level in patients with at least one enhancing lesion on brain MRI (3718 ng/L vs. 1589 ng/L; p=0.009), as well as in patients with at least 10 cells/mm3 in CSF (5044 ng/L vs. 2149 ng/L; p=0.031). Furthermore, we found that NFL level of CIS patients who later developed MS was significantly higher than in patients who remained CIS (3796 ng/L vs. 887 ng/L; p=0.025). We also observed a significant NFL level increase in patients with at least one clinical relapse after lumbar puncture (3954 ng/L vs. 1597 ng/L; p=0.001). In addition, patients with NfL level >2211 ng/L (i.e. median of study population) had a significantly shorter time to relapse (median 8.2 years vs 11.6 years; p=0.048). Finally, we found a significant correlation of NFL concentration with relapse rate (r=0.344, p< 0.001) and with expanded disability status scale score at one year after lumbar puncture (r=0.289, p=0.038).
Conclusion: Our findings suggest that CSF NFL is prominently a marker of acute inflammation in MS, as shown by the association with gadolinium-enhancing lesions on MRI, CSF pleocytosis, conversion from CIS to MS, shorter time to first relapse and relapse rate after lumbar puncture. CSF NFL level could be used to stratify CIS and relapsing-remitting MS patients according to disease activity and the correlated risk of subsequent disability, in order to identify cases eligible to early disease-modifying treatment.
Disclosure:
Dr. Calabrese received payment for development of educational presentations including service on speakers bureaus by Biogen-Elan, Genzyme, TEVA, Bayer-Schering; he received travel/accomodation expenses by Novartis Pharma, Genzyme, Biogen idec, Merck Serono, Bayer-Schering, TEVA, and Advisory Board membership by Bayer-Shering, Genzyme, Biogen Idec.
Dr. Gajofatto received speaker honoraria from Merck.
The study was supported by Cariverona Foundation.
Abstract: P625
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Introduction: Biomarkers of disease activity that have reliable prognostic utility in MS are lacking.
The aim of this study was to determine whether the level of neurofilament light chain (NFL) in the cerebrospinal fluid (CSF) of MS patients, correlates with disease activity and progression.
Methods: Between June 2015 and April 2016 we analyzed all available CSF samples from patients with clinically isolated syndrome (CIS) or MS, collected up to August 2014 and stored at Verona University Hospital. Clinical and MRI variables were obtained retrospectively from medical records. CSF standard examination and isoelectrofocusing for oligoclonal bands were performed at Verona University Hospital at the time of diagnostic lumbar puncture. NFL concentration was assessed using a commercially available ELISA kit.
Results: Of the 111 analyzed CSF samples, 25 were collected from CIS and 86 from MS patients
(72 with relapsing-remitting and 14 with progressive course). We observed a significant increase in CSF NFL level in patients with at least one enhancing lesion on brain MRI (3718 ng/L vs. 1589 ng/L; p=0.009), as well as in patients with at least 10 cells/mm3 in CSF (5044 ng/L vs. 2149 ng/L; p=0.031). Furthermore, we found that NFL level of CIS patients who later developed MS was significantly higher than in patients who remained CIS (3796 ng/L vs. 887 ng/L; p=0.025). We also observed a significant NFL level increase in patients with at least one clinical relapse after lumbar puncture (3954 ng/L vs. 1597 ng/L; p=0.001). In addition, patients with NfL level >2211 ng/L (i.e. median of study population) had a significantly shorter time to relapse (median 8.2 years vs 11.6 years; p=0.048). Finally, we found a significant correlation of NFL concentration with relapse rate (r=0.344, p< 0.001) and with expanded disability status scale score at one year after lumbar puncture (r=0.289, p=0.038).
Conclusion: Our findings suggest that CSF NFL is prominently a marker of acute inflammation in MS, as shown by the association with gadolinium-enhancing lesions on MRI, CSF pleocytosis, conversion from CIS to MS, shorter time to first relapse and relapse rate after lumbar puncture. CSF NFL level could be used to stratify CIS and relapsing-remitting MS patients according to disease activity and the correlated risk of subsequent disability, in order to identify cases eligible to early disease-modifying treatment.
Disclosure:
Dr. Calabrese received payment for development of educational presentations including service on speakers bureaus by Biogen-Elan, Genzyme, TEVA, Bayer-Schering; he received travel/accomodation expenses by Novartis Pharma, Genzyme, Biogen idec, Merck Serono, Bayer-Schering, TEVA, and Advisory Board membership by Bayer-Shering, Genzyme, Biogen Idec.
Dr. Gajofatto received speaker honoraria from Merck.
The study was supported by Cariverona Foundation.