January-February 2018
ADULT BRAIN

Thalamic Iron Differentiates Primary-Progressive and Relapsing-Remitting Multiple Sclerosis

Burgetova Pic

Andrea Burgetova

MRI markers reflecting iron concentration in deep gray matter (DGM), such as R2*/quantitative susceptibility mapping (QSM), correlate with clinical severity and to a fair degree predict the evolution of disability in MS.1 In addition to DGM deposits, iron accumulates in activated microglial cells in white matter lesions (WMLs), while the normal-appearing white matter is deprived of iron, suggesting large-scale derangement of CNS iron metabolism in MS that may be intimately related to neuroinflammatory processes.2 Our previous cross-sectional studies in MS brought evidence that iron accumulates in the DGM, that it is associated with disease severity, and that patterns of iron accumulation may differentiate between relapsing-remitting (RR) and primary progressive (PP) disease subtypes.3,4 Interestingly, we found decreased susceptibility within the thalamus in RRMS. In analyzing thalamic substructures, the difference in quantitative susceptibility between RRMS, PPMS, and healthy control groups was found to be most pronounced in the thalamus without the pulvinar.4 Significantly reduced magnetic susceptibility in RRMS compared with controls (whole thalamus excluding the pulvinar nucleus) has also been observed by Schweser et al.5

Brain iron homeostasis is known to be disturbed in MS, yet there is only a limited understanding of whether and how neuroimaging abnormalities are related to biochemical and immunologic parameters in blood and CSF. Linking to our previous research, we have started a new project, “Quantitative Susceptibility Mapping with MRI and Biochemical Profiling of Biological Fluids in Multiple Sclerosis.” This project is aimed at investigating MRI blood and CSF biomarkers related to iron metabolism that would reflect clinical severity and predict long-term outcomes in de novo patients with MS. Through metalloproteomic and iron metabolite profiling of blood and CSF, we aim to identify biochemical parameters linking immunologic disease activity with iron deposits in the DGM/WML. We will examine whether the number of QSM-positive (iron-containing) lesions correlates with iron concentration in the DGM.

With the wealth of modern disease-modifying therapies with different mechanisms of action, there is an urgent need for novel, reliable biomarkers of MS with theranostic values. The longitudinal setting of this study, along with multiparametric MRI and biochemical biomarkers, may help identify subgroups of patients with MS with different pathophysiologies and

responsiveness to treatment. Finding biomarkers with strong predictive values toward disease may help us better understand the pathophysiologic pathways of the disease.

References

  1. Khalil M, Langkammer C, Pichler A, et al. Dynamics of brain iron levels in multiple sclerosis: a longitudinal 3T MRI studyNeurology 2015;84:2396–402, 10.1212/WNL.0000000000001679.
  2. Hametner S, Wimmer I, Haider L, et al. Iron and neurodegeneration in the multiple sclerosis brainAnn Neurol 2013;74:848–61, 10.1002/ana.23974
  3. Burgetova A, Seidl Z, Krasensky J, et al. Multiple sclerosis and the accumulation of iron in the basal ganglia: quantitative assessment of brain iron using MRI t(2) relaxometryEur Neurol 2010;63:136–43, 10.1159/000279305
  4. Burgetova A, Dusek P, Vaneckova M, et al. Thalamic iron differentiates primary-progressive and relapsing-remitting multiple sclerosisAJNR Am J Neuroradiol 2017;38:1079–86, 10.3174/ajnr.A5166
  5. Schweser F, Duarte Martins ALR, Hagemeier J, et al. Mapping of thalamic magnetic susceptibility in multiple sclerosis indicates decreasing iron with disease duration: a proposed mechanistic relationship between inflammation and oligodendrocyte vitalityNeuroImage 2017. [Epub ahead of print]

Read this article at AJNR.org …