Format

Send to

Choose Destination
Mult Scler. 2016 Aug;22(9):1154-62. doi: 10.1177/1352458516645206. Epub 2016 May 11.

Elevated CSF neurofilament proteins predict brain atrophy: A 15-year follow-up study.

Author information

1
Department of Neurology and Ophthalmology, VUmc MS Center Amsterdam, VU University Medical Center, Neuroscience Campus, Amsterdam, The Netherlands/Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK a.petzold@ucl.ac.uk a.petzold@vumc.nl.
2
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands/Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands.
3
Westfriesgasthuis, Hoorn, The Netherlands.
4
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
5
Department of Neurology, VUmc MS Center Amsterdam, VU University Medical Center, Neuroscience Campus, Amsterdam, The Netherlands.

Abstract

BACKGROUND:

Body fluid and structural imaging biomarkers give information on neurodegeneration. The relationship over time is not known in multiple sclerosis.

OBJECTIVE:

To investigate the temporal relationship of elevated cerebrospinal fluid (CSF) neurofilament (Nf) protein levels, a biomarker for axonal loss, with magnetic resonance imaging (MRI) atrophy measures.

METHODS:

In patients with multiple sclerosis, CSF Nf heavy chain (NfH) phosphoform levels were quantified at baseline and dichotomised into 'normal' and 'high'. Atrophy was assessed by MRI at baseline and 15-year follow-up using SIENAX and FreeSurfer software.

RESULTS:

High baseline CSF NfH(SMI35) levels predicted pronounced atrophy at 15-year follow-up (odds ratio (OR): 36, p < 0.01), in the absence of baseline brain atrophy (OR: 28, p < 0.05), for the averaged MRI normalised brain volume (1.44 L vs 1.33 L, p < 0.05), normalised grey matter volume (0.77 L vs 0.69 L, p < 0.01) and putamen (12.7 mL vs 10.7 mL, p < 0.05). Region-specific calculations including the spinal cord showed that a power of >80% is reached with 14-50 patients.

CONCLUSION:

These data suggest that high CSF NfH levels are an early predictor of later brain and spinal cord atrophy using structural imaging biomarkers and can be investigated in reasonably sized patient cohorts.

KEYWORDS:

CSF; Neurodegeneration; biomarker; cerebrospinal fluid; multiple sclerosis; neurofilaments

PMID:
27207456
DOI:
10.1177/1352458516645206
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center