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Mult Scler Relat Disord. 2014 Mar;3(2):194-202. doi: 10.1016/j.msard.2013.06.017. Epub 2013 Jul 30.

Increased deep gray matter iron is present in clinically isolated syndromes.

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Department of Medical Biophysics, The University of Western Ontario, Canada; Centre for Functional and Metabolic Mapping, Robarts Research Institute, The University of Western Ontario, Canada.
Centre for Functional and Metabolic Mapping, Robarts Research Institute, The University of Western Ontario, Canada.
Department of Medical Imaging, The University of Western Ontario, Canada.
Department of Clinical Neurological Sciences, The University of Western Ontario, London Health Sciences Centre, University Hospital, 339 Windermere Road, London, Ontario, Canada, N6A 5A5. Electronic address:



Abnormal iron accumulation in MS has been known for decades, however it remains to be established whether iron reflects a cause or epiphenomenon of pathology. The objective of the present study is to determine if iron is increased in the brains of patients with clinically isolated syndromes (CIS) suggestive of early MS.


Twenty-two patients with a CIS and 16 age- and sex-matched controls underwent 3T MRI studies. Differences in R2*, a metric of iron concentration, were assessed for all voxels throughout the brain. Similar clusters of significant differences were grouped, wherein mean R2* was regressed against a number of parameters, including extended disability status scale (EDSS), age, disease duration, and internal jugular vein (IJV) cross-sectional area (CSA), as measured from magnetic resonance time-of-flight venograms.


Patients had significantly increased R2* in globus pallidus, thalamus, right pulvinar, and cortical areas. Thalamic R2* correlated positively with EDSS. Decreased white matter R2* was detected at various positions in the patient group average. No correlations were found between any changes in R2* and IJV CSA.


Iron is increased in CIS in deep gray matter, suggesting this iron accumulation, well-known in definite MS, occurs early in the disease course. Increases in thalamic iron are associated with worsened clinical status. Decreased white matter R2* may be interpreted as diffuse damage to normal appearing white matter, not often reported in CIS. Observations do not support a role for venous abnormalities in either iron accumulation or white matter damage.


Clinically isolated syndrome; Deep grey matter; Disease progression; High field MRI; Iron; Multiple sclerosis

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