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Abstract

Background:

The role of biomarkers to predict clinical outcome in multiple sclerosis (MS) is still debated.

Objective:

To test whether cerebrospinal fluid (CSF) light-chain neurofilament (NfL) levels in newly diagnosed patients with MS could predict clinical outcome over a 10-year period.

Methods:

Patients with newly diagnosed MS underwent standardized clinical assessments at baseline and 5 and 10 years of follow-up. Expanded Disability Status Scale (EDSS) progression between assessments was defined as an increase in one point or more if <6 and 0.5 or more if ≥6. CSF obtained at baseline was analyzed for levels of NfL using enzyme-linked immunosorbent assay technology.

Results:

A total of 44 patients were included. In all, 35 patients (80%) had relapsing–remitting multiple sclerosis (RRMS). Patients who progressed in EDSS showed a trend for higher median baseline CSF-NfL levels than patients who did not progress after 5 years (947 ng/L vs 246 ng/L, p = 0.05), and although not statistically significant, after 10 years (708 ng/L vs 265 ng/L, p = 0.28). Patients who converted from RRMS to secondary-progressive multiple sclerosis (SPMS) at 5 years had a statistical significant higher median CSF level of NfL (2122 ng/L vs 246 ng/L, p = 0.01).

Conclusion:

CSF levels of NfL at the time of diagnosis seems to be an early predictive biomarker of long-term clinical outcome and conversion from RRMS to SPMS.

Keywords

Multiple sclerosis biomarkers neurofilaments cerebrospinal fluid disease progression magnetic resonance imaging

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References

Hauser

Oksenberg

. The neurobiology of multiple sclerosis: Genes, inflammation, and neurodegeneration. Neuron 2006; 52: 61–76.

Grytten

Glad

Aarseth

et al . A 50-year follow-up of the incidence of multiple sclerosis in Hordaland County, Norway. Neurology 2006; 66: 182–186.

Jacobsen

Hagemeier

Myhr

et al . Brain atrophy and disability progression in multiple sclerosis patients: A 10-year follow-up study. J Neurol Neurosurg Psychiatry 2014; 85: 1109–1115.

Goodin

The use of MRI in the diagnosis of multiple sclerosis. Lancet Neurol 2006; 5: 808–809.

Tintore

Rovira

Rio

et al . Defining high, medium and low impact prognostic factors for developing multiple sclerosis. Brain 2015; 138: 1863–1874.

Teunissen

Khalil

Neurofilaments as biomarkers in multiple sclerosis. Mult Scler 2012; 18: 552–556.

Haghighi

Andersen

Oden

et al . Cerebrospinal fluid markers in MS patients and their healthy siblings. Acta Neurol Scand 2004; 109: 97–99.

Amor

van der Star

Bosca

et al . Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis. Mult Scler 2014; 20: 1355–1362.

Petzold

Eikelenboom

Keir

et al . Axonal damage accumulates in the progressive phase of multiple sclerosis: Three year follow up study. J Neurol Neurosurg Psychiatry 2005; 76: 206–211.

10.

Teunissen

Iacobaeus

Khademi

et al . Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis. Neurology 2009; 72: 1322–1329.

11.

Varhaug

Barro

Bjørnevik

et al . Neurofilament light chain predicts disease activity in relapsing remitting multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2017; 5(1): e422.

12.

Poser

Paty

Scheinberg

et al . New diagnostic criteria for multiple sclerosis: Guidelines for research protocols. Ann Neurol 1983; 13: 227–231.

13.

Petzold

Altintas

Andreoni

et al . Neurofilament ELISA validation. J Immunol Methods 2010; 352: 23–31.

14.

Kuhle

Plattner

Bestwick

et al . A comparative study of CSF neurofilament light and heavy chain protein in MS. Mult Scler 2013; 19: 1597–1603.

15.

Salzer

Svenningsson

Sundstrom

Neurofilament light as a prognostic marker in multiple sclerosis. Mult Scler 2010; 16: 287–292.

16.

Gunnarsson

Malmestrom

Axelsson

et al . Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann Neurol 2011; 69: 83–89.

17.

Kuhle

Disanto

Lorscheider

et al . Fingolimod and CSF neurofilament light chain levels in relapsing-remitting multiple sclerosis. Neurology 2015; 84: 1639–1643.

18.

Thompson

Banwell

Barkhof

et al . Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2017; 17: 162–173.

19.

Norgren

Sundstrom

Svenningsson

et al . Neurofilament and glial fibrillary acidic protein in multiple sclerosis. Neurology 2004; 63: 1586–1590.

20.

Kuhle

Barro

Andreasson

et al . Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med 2016; 54: 1655–1661.

21.

Bergman

Dring

Zetterberg

et al . Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS. Neurol Neuroimmunol Neuroinflamm 2016; 3: e271.

22.

Kuhle

Barro

Disanto

et al . Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity. Mult Scler 2016; 22: 1550–1559.

23.

Kuhle

Nourbakhsh

Grant

et al . Serum neurofilament is associated with progression of brain atrophy and disability in early MS. Neurology 2017; 88: 826–831.

24.

Disanto

Barro

Benkert

et al . Serum neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol 2017; 81: 857–870.

25.

Daumer

Neuhaus

Morrissey

et al . MRI as an outcome in multiple sclerosis clinical trials. Neurology 2009; 72: 705–711.

26.

University of California, San Francisco MS-EPIC Team, Cree

Gourraud

et al . Long-term evolution of multiple sclerosis disability in the treatment era. Ann Neurol 2016; 80: 499–510.

Neurofilaments and 10-year follow-up in multiple sclerosis

Abstract

Background:

Objective:

Methods:

Results:

Conclusion:

Keywords

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References