Sage Journals: Discover world-class research

Abstract

Background:

Increase of brain total sodium concentrations (TSC) is present in multiple sclerosis (MS), but its pathological involvement has not been assessed yet.

Objective:

To determine in vivo the metabolic counterpart of brain sodium accumulation.

Materials/methods:

Whole brain ²³Na-MR imaging and 3D-¹H-EPSI data were collected in 21 relapsing-remitting multiple sclerosis (RRMS) patients and 20 volunteers. Metabolites and sodium levels were extracted from several regions of grey matter (GM), normal-appearing white matter (NAWM) and white matter (WM) T₂ lesions. Metabolic and ionic levels expressed as Z-scores have been averaged over the different compartments and used to explain sodium accumulations through stepwise regression models.

Results:

MS patients showed significant ²³Na accumulations with lower choline and glutamate–glutamine (Glx) levels in GM; ²³Na accumulations with lower N-acetyl aspartate (NAA), Glx levels and higher Myo-Inositol (m-Ins) in NAWM; and higher ²³Na, m-Ins levels with lower NAA in WM T₂ lesions. Regression models showed associations of TSC increase with reduced NAA in GM, NAWM and T₂ lesions, as well as higher total-creatine, and smaller decrease of m-Ins in T₂ lesions. GM Glx levels were associated with clinical scores.

Conclusion:

Increase of TSC in RRMS is mainly related to neuronal mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM is linked to clinical scores.

Keywords

MRSI multiple sclerosis stepwise regression neurodegeneration demyelination

Get full access to this article

View all access options for this article.

References

Kutzelnigg

Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005; 128(11): 2705–2712.

Smith

KJ.

Sodium channels and multiple sclerosis: Roles in symptom production, damage and therapy. Brain Pathol 2007; 17(2): 230–242.

Freeman

Desmazières

Fricker

et al . Mechanisms of sodium channel clustering and its influence on axonal impulse conduction. Cell Mol Life Sci 2016; 73(4): 723–735.

Waxman

SG.

Axonal conduction and injury in multiple sclerosis: The role of sodium channels. Nat Rev Neurosci 2006; 7(12): 932–941.

Hilal

Maudsley

et al . In vivo NMR imaging of sodium-23 in the human head. J Comput Assist Tomogr 1985; 9(1): 1–7.

Eisele

Konstandin

Griebe

et al . Heterogeneity of acute multiple sclerosis lesions on sodium (23Na) MRI. Mult Scler 2016; 22(8): 1040–1047.

Inglese

Madelin

Oesingmann

et al . Brain tissue sodium concentration in multiple sclerosis: A sodium imaging study at 3 tesla. Brain 2010; 133(3): 847–857.

Zaaraoui

Konstandin

Audoin

et al . Distribution of brain sodium accumulation correlates with disability in multiple sclerosis: A cross-sectional 23Na MR imaging study. Radiology 2012; 264(3): 859–867.

Maarouf

Audoin

Pariollaud

et al . Increased total sodium concentration in gray matter better explains cognition than atrophy in MS. Neurology 2017; 88(3): 289–295.

10.

Maarouf

Audoin

Konstandin

et al . Topography of brain sodium accumulation in progressive multiple sclerosis. Magn Reson Mater Phys Biol Med 2013; 27(1): 53–62.

11.

Paling

Solanky

Riemer

et al . Sodium accumulation is associated with disability and a progressive course in multiple sclerosis. Brain 2013; 136(7): 2305–2317.

12.

Thulborn

KR.

Quantitative Sodium MR Imaging: A review of its evolving role in medicine. Neuroimage 2016; pii: S1053–8119(16)30674–30677.

13.

Petracca

Vancea

Fleysher

et al . Brain intra- and extracellular sodium concentration in multiple sclerosis: A 7 T MRI study. Brain 2016; 139(3): 795–806.

14.

Madelin

Babb

Xia

et al . Repeatability of quantitative sodium magnetic resonance imaging for estimating pseudo-intracellular sodium concentration and pseudo-extracellular volume fraction in brain at 3 T. Plos One 2015; 10(3): e0118692.

15.

Moffett

Ross

Arun

et al . N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology. Prog Neurobiol 2007; 81(2): 89–131.

16.

Rae

CD.

A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res 2014; 39(1): 1–36.

17.

Kirov

Tal

Babb

et al . Serial proton MR spectroscopy of gray and white matter in relapsing-remitting MS. Neurology 2013; 80(1): 39–46.

18.

Lassmann

Mechanisms of white matter damage in multiple sclerosis. Glia 2014; 62(11): 1816–1830.

19.

Lecocq

Le Fur

Maudsley

et al . Whole-brain quantitative mapping of metabolites using short echo three-dimensional proton MRSI. J Magn Reson Imaging 2015; 42(2): 280–289.

20.

Donadieu

Le Fur

Lecocq

et al . Metabolic voxel-based analysis of the complete human brain using fast 3D-MRSI: Proof of concept in multiple sclerosis. J Magn Reson Imaging 2016; 44(2): 411–419.

21.

Nagel

Laun

Weber

M-A

et al . Sodium MRI using a density-adapted 3D radial acquisition technique. Magn Reson Med 2009; 62(6): 1565–1573.

22.

Fernando

KTM

McLean

Chard

et al . Elevated white matter myo-inositol in clinically isolated syndromes suggestive of multiple sclerosis. Brain 2004; 127(6): 1361–1369.

23.

Vingara

Wagshul

et al . Metabolomic approach to human brain spectroscopy identifies associations between clinical features and the frontal lobe metabolome in multiple sclerosis. Neuroimage 2013; 82: 586–594.

24.

Hattingen

Magerkurth

Pilatus

et al . Combined 1H and 31P spectroscopy provides new insights into the pathobiochemistry of brain damage in multiple sclerosis. NMR Biomed 2011; 24(5): 536–546.

25.

Geurts

JJG

Reuling

IEW

Vrenken

et al . MR spectroscopic evidence for thalamic and hippocampal, but not cortical, damage in multiple sclerosis. Magn Reson Med 2006; 55(3): 478–483.

26.

Witte

Mahad

Lassmann

et al . Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis. Trends Mol Med 2014; 20(3): 179–187.

27.

Srinivasan

Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain 2005; 128(5): 1016–1025.

28.

MacMillan

Tam

Zhao

et al . Progressive multiple sclerosis exhibits decreasing glutamate and glutamine over two years. Mult Scler 2016; 22(1): 112–116.

29.

Kirischuk

Héja

Kardos

et al . Astrocyte sodium signaling and the regulation of neurotransmission. Glia 2016; 64(10): 1655–1666.

30.

Boscia

Begum

Pignataro

et al . Glial Na(+) -dependent ion transporters in pathophysiological conditions. Glia 2016; 64(10): 1677–1697.

31.

Centonze

Muzio

Rossi

et al . The link between inflammation, synaptic transmission and neurodegeneration in multiple sclerosis. Cell Death Differ 2010; 17(7): 1083–1091.

32.

Klauser

Wiebenga

Eijlers

et al . Metabolites predict lesion formation and severity in relapsing-remitting multiple sclerosis. Mult Scler 2018; 24: 491–500.

33.

Praet

Orije

Kara

et al . Cuprizone-induced demyelination and demyelination-associated inflammation result in different proton magnetic resonance metabolite spectra. NMR Biomed 2015; 28(4): 505–513.

34.

Fleischer

Kolb

Groppa

et al . Metabolic patterns in chronic multiple sclerosis lesions and normal-appearing white matter: Intraindividual comparison by using 2D MR spectroscopic imaging. Radiology 2016; 281(2): 536–543.

35.

Sabati

Sheriff

et al . Multivendor implementation and comparison of volumetric whole-brain echo-planar MR spectroscopic imaging. Magn Reson Med 2015; 74(5): 1209–1220.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.48 MB

0.30 MB

0.11 MB

Metabolic counterparts of sodium accumulation in multiple sclerosis: A whole brain 23 Na-MRI and fast 1 H-MRSI study

Abstract

Background:

Objective:

Materials/methods:

Results:

Conclusion:

Keywords

Get full access to this article

References

Supplementary Material