Contributions
Abstract: P1171
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Neurofilament light chain (NfL) is released in axonal injury, and has been proposed as a potential biomarker for monitoring disease activity in people with multiple sclerosis (pwMS). Our objective was to systematically review and perform a meta-analysis of case-control studies that measured NfL levels in cerebrospinal fluid (CSF) of pwMS, in order to determine to what extent CSF NfL differentiates pwMS from control populations, or different subtypes or stages of MS from each other.
Methods: Guidelines on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2009 (PRISMA) were followed. Electronic databases were searched for published and grey literature, resulting in 151 hits. Fifty-one full articles were screened, 20 were included in qualitative analysis, and 14 in our meta-analysis.
Results: CSF NfL was higher in 746 MS patients than 435 (healthy and disease) controls - 1965.8ng/L, SD 3102.5, vs 578.3ng/L, SD 1212.3, with a moderate effect size on meta-analysis, 0.61, p< 0.00001.
In 259 relapsing-remitting MS (RRMS) patients, CSF NfL was five times higher than controls in remission, and nine times higher than controls in relapse. No difference was found in CSF NfL levels between 48 primary and 75 secondary progressive MS cases.
176 RRMS patients had a significantly higher mean CSF NfL (2124.8 ng/l, SD 3348.9) than 92 progressive patients (1121.4 ng/L, SD 947.7) (p=0.0108). However, when only RRMS patients in remission were included in this analysis, differences in CSF NfL levels did not reach statistical significance. Meta-analysis of CSF NfL levels in relapse vs remission across all pwMS (combined RRMS and progressive MS) revealed higher NfL levels in relapse, and a statistically significant moderate effect size, 0.56, p< 0.0001.
Conclusion: Our results suggest that CSF NfL levels correlate with MS activity throughout the disease course, reflecting the axonal damage that occurs during active disease, and not as a late consequence of demyelination. CSF NfL is higher in relapse than in remission, but does not distinguish between RRMS in remission and progressive MS, and its value as a predictor of long term outcome is unclear. Relapse, causing acute axonal loss, appears to be a stronger driver of CSF NfL levels than progressive disease states associated with chronic neuro-axonal loss, and NfL may therefore have greater clinical utility as a biomarker of 'disease activity' than 'disease progression'.
Disclosure: Dr Sarah-Jane Martin has received travel grants for attending neurology conferences from Biogen and Merck.
Dr Sarah McGlasson and Dr David Hunt report nothing to disclosure.
Dr James Overell has received honoraria for speaking engagements, involvement in educational initiatives and participation in advisory boards from: Teva, Novartis, Merck Serono, Genzyme, Roche, Allergan, Imcyse and Biogen. Research project funding from: Genzyme and Biogen. Travel grants for attendance at conferences: Biogen, Genzyme, Novartis, Roche, Merck Serono and Teva. Departmental educational grants and funds to provide nursing and administrative staff: Novartis, Genzyme, Roche, and Biogen.
Abstract: P1171
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Neurofilament light chain (NfL) is released in axonal injury, and has been proposed as a potential biomarker for monitoring disease activity in people with multiple sclerosis (pwMS). Our objective was to systematically review and perform a meta-analysis of case-control studies that measured NfL levels in cerebrospinal fluid (CSF) of pwMS, in order to determine to what extent CSF NfL differentiates pwMS from control populations, or different subtypes or stages of MS from each other.
Methods: Guidelines on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2009 (PRISMA) were followed. Electronic databases were searched for published and grey literature, resulting in 151 hits. Fifty-one full articles were screened, 20 were included in qualitative analysis, and 14 in our meta-analysis.
Results: CSF NfL was higher in 746 MS patients than 435 (healthy and disease) controls - 1965.8ng/L, SD 3102.5, vs 578.3ng/L, SD 1212.3, with a moderate effect size on meta-analysis, 0.61, p< 0.00001.
In 259 relapsing-remitting MS (RRMS) patients, CSF NfL was five times higher than controls in remission, and nine times higher than controls in relapse. No difference was found in CSF NfL levels between 48 primary and 75 secondary progressive MS cases.
176 RRMS patients had a significantly higher mean CSF NfL (2124.8 ng/l, SD 3348.9) than 92 progressive patients (1121.4 ng/L, SD 947.7) (p=0.0108). However, when only RRMS patients in remission were included in this analysis, differences in CSF NfL levels did not reach statistical significance. Meta-analysis of CSF NfL levels in relapse vs remission across all pwMS (combined RRMS and progressive MS) revealed higher NfL levels in relapse, and a statistically significant moderate effect size, 0.56, p< 0.0001.
Conclusion: Our results suggest that CSF NfL levels correlate with MS activity throughout the disease course, reflecting the axonal damage that occurs during active disease, and not as a late consequence of demyelination. CSF NfL is higher in relapse than in remission, but does not distinguish between RRMS in remission and progressive MS, and its value as a predictor of long term outcome is unclear. Relapse, causing acute axonal loss, appears to be a stronger driver of CSF NfL levels than progressive disease states associated with chronic neuro-axonal loss, and NfL may therefore have greater clinical utility as a biomarker of 'disease activity' than 'disease progression'.
Disclosure: Dr Sarah-Jane Martin has received travel grants for attending neurology conferences from Biogen and Merck.
Dr Sarah McGlasson and Dr David Hunt report nothing to disclosure.
Dr James Overell has received honoraria for speaking engagements, involvement in educational initiatives and participation in advisory boards from: Teva, Novartis, Merck Serono, Genzyme, Roche, Allergan, Imcyse and Biogen. Research project funding from: Genzyme and Biogen. Travel grants for attendance at conferences: Biogen, Genzyme, Novartis, Roche, Merck Serono and Teva. Departmental educational grants and funds to provide nursing and administrative staff: Novartis, Genzyme, Roche, and Biogen.