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Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).ORCID iD: 0000-0002-8857-5698
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
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2017 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 1, 112-121 p.Article in journal (Refereed) Published
Abstract [en]

Background and purpose

Brain atrophy is related to clinical deterioration in multiple sclerosis (MS) but its association with intrathecal markers of inflammation or neurodegeneration is unclear. Our aim was to investigate whether cerebrospinal fluid (CSF) markers of inflammation or neurodegeneration are associated with brain volume change in natalizumab-treated MS and whether this change is reflected in non-lesional white matter metabolites.

Methods

About 25 patients with natalizumab-treated MS were followed for 3 years with assessment of percentage brain volume change (PBVC) and absolute quantification of metabolites with proton magnetic resonance spectroscopy (1H MRS). Analyses of inflammatory [interleukin 1β (IL-1β), IL-6, C-X-C motif chemokine 8 (CXCL8), CXCL10, CXCL11, C-C motif chemokine 22] and neurodegenerative [neurofilament light protein (NFL), glial fibrillary acidic protein, myelin basic protein, tau proteins] markers were done at baseline and 1-year follow-up.

Results

The mean decline in PBVC was 3% at the 3-year follow-up, although mean 1H MRS metabolite levels in non-lesional white matter were unchanged. CSF levels of NFL and tau at baseline correlated negatively with PBVC over 3 years (r = −0.564, P = 0.012, and r = −0.592, P = 0.010, respectively).

Conclusions

A significant 3-year whole-brain atrophy was not reflected in mean metabolite change of non-lesional white matter. In addition, our results suggest that CSF levels of NFL and tau correlate with brain atrophy development and may be used for evaluating treatment response in inflammatory active MS.

Place, publisher, year, edition, pages
Blackwell Publishing, 2017. Vol. 24, no 1, 112-121 p.
Keyword [en]
brain atrophy, magnetic resonance spectroscopy, multiple sclerosis, natalizumab, neurofilament, quantitative magnetic resonance imaging, tau
National Category
Neurology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:liu:diva-134153DOI: 10.1111/ene.13162ISI: 000392806700007OAI: oai:DiVA.org:liu-134153DiVA: diva2:1068741
Note

Funding agencies: Medical Research Council [K2013-61X-22310-01-4]; Swedish Society of Neurologically Disabled; Swedish Society of Medicine; National Research Council (VR/NT); Linkoping University; Linkoping University Hospital; County Council of Ostergotland

Available from: 2017-01-26 Created: 2017-01-26 Last updated: 2017-11-29

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Mellergård, JohanTisell, AndersBlystad, IdaGrönqvist, AndersDahle, CharlotteVrethem, MagnusLundberg, PeterErnerudh, Jan
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Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesDepartment of NeurologyDepartment of Medical and Health SciencesDepartment of Radiation PhysicsCenter for Medical Image Science and Visualization (CMIV)Division of Radiological SciencesDepartment of Radiology in LinköpingDepartment of Clinical Immunology and Transfusion Medicine
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