Abstract
Purpose
The present study was carried out to investigate any possible linkage between cerebral
grey matter volumetric, iron changes, white matter's lesions load and serum iron levels
in a group of relapsing-remitting multiple sclerosis (RRMS) patients.
Materials and methods
Sixty-five RRMS patients along with thirty-four age-matched healthy controls (HCs)
were recruited. Serum samples were isolated from blood samples which were collected
in vacutainer plain tubes individually from both groups. Both groups were scanned
at 1.5 T magnetic resonance imaging (MRI) using the following 3D sequences; T1-weighted
gradient echo (MPRAGE), T2*-weighted gradient echo and T2-weighted fluid-attenuated
inversion recovery (FLAIR).
Results
Significant differences were observed between the RRMS patients and HCs for cortical
and deep grey matter (dGM) volumes where cortical and dGM volumes in RRMS patient
were significantly smaller than those in HCs. While iron deposition in the cortex,
putamen (PT) and globus pallidus (GP) of RRMS patients were significantly higher than
those of HCs, iron levels in thalamus (TH) and serum were significantly lower in RRMS
compared to those in HCs. Except for T2 lesion load, none of volumetric measures showed
any association with patients' disability status. Cerebral grey matter's iron changes
did not show any association with those of serum.
Conclusion
Smaller cortical and subcortical grey matter volumes in RRMS patients compared to
HCs were detected. None of the volumetric measures showed any association with patients'
disability status. RRMS patients showed increased iron levels in the PT, GP and cortex
and decreased levels in the TH and serum.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical ImagingAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Endogenous remyelination is induced by transplant rejection in a viral model of multiple sclerosis.J Neuroimmunol. 2009; 212: 74-81https://doi.org/10.1016/j.jneuroim.2009.05.002
- Increased iron accumulation occurs in the earliest stages of demyelinating disease: an ultra-high field susceptibility mapping study in Clinically Isolated Syndrome.Mult Scler. 2013; 19: 896-903https://doi.org/10.1177/1352458512465135
- The effect of age on the non-haemin iron in the human brain.J Neurochem. 1958; 3: 41-51https://doi.org/10.1111/j.1471-4159.1958.tb12607.x
- Iron levels in the human brain: a post-mortem study of anatomical region differences and age-related changes.J Trace Elem Med Biol. 2014; 28: 13-17https://doi.org/10.1016/j.jtemb.2013.08.001
- 7 Tesla magnetic resonance imaging to detect cortical pathology in multiple sclerosis.PLoS One. 2014; 9e108863https://doi.org/10.1371/journal.pone.0108863
- Brain trace elements and aging.Nucl Instruments Methods Phys Res Sect B Beam Interact Mater Atoms. 1999; 150: 208-213https://doi.org/10.1016/S0168-583X(98)00938-0
- Cortical and subcortical morphometric and iron changes in relapsing-remitting multiple sclerosis and their association with white matter T2 lesion load.Clin Neuroradiol. 2019; 29: 51-64
- Quantitative in vivo magnetic resonance imaging of multiple sclerosis at 7 Tesla with sensitivity to iron.Ann Neurol. 2008; 64: 707-713https://doi.org/10.1002/ana.21582
- In vivo assessment of iron content of the cerebral cortex in healthy aging using 7-Tesla T2*-weighted phase imaging.Neurobiol Aging. 2017; 53: 20-26https://doi.org/10.1016/j.neurobiolaging.2016.09.005
- Impairment of interrelated Iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders.Front Pharmacol. 2012; 3: 169https://doi.org/10.3389/fphar.2012.00169
- Serum iron concentration is associated with subcortical deep gray matter iron levels in multiple sclerosis patients.Neuroreport. 2017; 28: 645-648https://doi.org/10.1097/WNR.0000000000000804
- Association between anemia and multiple sclerosis.Eur Neurol. 2015; 73: 233-237https://doi.org/10.1159/000381212
- Mapping deep gray matter iron in multiple sclerosis by using quantitative magnetic susceptibility.Radiology. 2018; 289: 497-498https://doi.org/10.1148/radiol.2018181274
- Relationship between iron accumulation and white matter injury in multiple sclerosis: a case-control study.J Neurol. 2015; 262: 402-409https://doi.org/10.1007/s00415-014-7569-3
- Susceptibility weighted imaging in MRI: basic concepts and clinical applications.1st ed. Wiley-Blackwell, Hoboken, New Jersy2011
- Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain.Neuron. 2002; 33: 341-355
- Cortical surface-based analysis.Neuroimage. 1999; 9: 179-194
- Cortical surface-based analysis.Neuroimage. 1999; 9: 195-207
- Regional variations in the extent and pattern of grey matter demyelination in multiple sclerosis: a comparison between the cerebral cortex, cerebellar cortex, deep grey matter nuclei and the spinal cord.J Neurol Neurosurg Psychiatry. 2009; 80: 182-187
- Demyelination, inflammation, and neurodegeneration in multiple sclerosis deep gray matter.J Neuropathol Exp Neurol. 2009; 68: 489-502
- Grey matter pathology in multiple sclerosis.J Neuropathol Exp Neurol. 2005; 64: 1101-1107
- Extent of cerebellum, subcortical and cortical atrophy in patients with MS.J Neurol Sci. 2009; 282: 47-54
- Regional gray matter atrophy in relapsing remitting multiple sclerosis: baseline analysis of multi-center data.Mult Scler Relat Disord. 2015; 4: 124-136
- Focal cortical atrophy in multiple sclerosis: relation to lesion load and disability.Neuroimage. 2007; 34: 509-517https://doi.org/10.1016/j.neuroimage.2006.10.006
- Cortical thickness and surface area relate to specific symptoms in early relapsing–remitting multiple sclerosis.Mult Scler J. 2015; 21: 402-414https://doi.org/10.1177/1352458514543811
- Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study.J Neurol Neurosurg Psychiatry. 2014; 85: 1109-1115https://doi.org/10.1136/jnnp-2013-306906
- Gray matter damage predicts the accumulation of disability 13 years later in MS.Neurology. 2013; 81: 1759-1767https://doi.org/10.1212/01.wnl.0000435551.90824.d0
- Imaging cortical damage and dysfunction in multiple sclerosis.JAMA Neurol. 2013; 70: 556https://doi.org/10.1001/jamaneurol.2013.1954
- Gray matter atrophy is related to long-term disability in multiple sclerosis.Ann Neurol. 2008; 64: 247-254https://doi.org/10.1002/ana.21423
- Identification of common genetic modifiers of neurodegenerative diseases from an integrative analysis of diverse genetic screens in model organisms.BMC Genomics. 2012; 13: 71https://doi.org/10.1186/1471-2164-13-71
- Iron deposition in the gray matter in patients with relapse-remitting multiple sclerosis: a longitudinal study using three-dimensional (3D)-enhanced T2*-weighted angiography (ESWAN).Eur J Radiol. 2015; 84: 1325-1332https://doi.org/10.1016/j.ejrad.2015.04.013
- Mapping of thalamic magnetic susceptibility in multiple sclerosis indicates decreasing iron with disease duration: a proposed mechanistic relationship between inflammation and oligodendrocyte vitality.Neuroimage. 2018; 167: 438-452
- Brain iron at quantitative MRI is associated with disability in multiple sclerosis.Radiology. 2018; 289: 487-496
- Brain iron deposition in Parkinson’s disease imaged using the PRIME magnetic resonance sequence.Brain. 2000; 123: 2423-2431https://doi.org/10.1093/brain/123.12.2423
- The role of iron in the pathogenesis of experimental allergic encephalomyelitis and multiple sclerosis.Ann N Y Acad Sci. 2004; 1012: 252-266https://doi.org/10.1196/annals.1306.021
- Serum ferritin, transferrin and soluble transferrin receptor levels in multiple sclerosis patients.Mult Scler J. 2005; 11: 272-275https://doi.org/10.1191/1352458505ms1171oa
- The conundrum of iron in multiple sclerosis – time for an individualised approach.Metab Brain Dis. 2012; 27: 239-253https://doi.org/10.1007/s11011-012-9290-1
Article info
Publication history
Published online: September 19, 2020
Accepted:
September 11,
2020
Received in revised form:
August 17,
2020
Received:
June 25,
2020
Identification
Copyright
© 2020 Elsevier Inc. All rights reserved.