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June 16, 2015; 84 (24) Article

Dynamics of brain iron levels in multiple sclerosis

A longitudinal 3T MRI study

Michael Khalil, Christian Langkammer, Alexander Pichler, Daniela Pinter, Thomas Gattringer, Gerhard Bachmaier, Stefan Ropele, Siegrid Fuchs, Christian Enzinger, Franz Fazekas
First published May 15, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001679
Michael Khalil
From the Department of Neurology (M.K., C.L., A.P., D.P., T.G., S.R., S.F., C.E., F.F.), Department of Radiology (Division of Neuroradiology) (C.E.), and Institute for Medical Informatics, Statistics and Documentation (G.B.), Medical University of Graz, Austria.
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Christian Langkammer
From the Department of Neurology (M.K., C.L., A.P., D.P., T.G., S.R., S.F., C.E., F.F.), Department of Radiology (Division of Neuroradiology) (C.E.), and Institute for Medical Informatics, Statistics and Documentation (G.B.), Medical University of Graz, Austria.
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Alexander Pichler
From the Department of Neurology (M.K., C.L., A.P., D.P., T.G., S.R., S.F., C.E., F.F.), Department of Radiology (Division of Neuroradiology) (C.E.), and Institute for Medical Informatics, Statistics and Documentation (G.B.), Medical University of Graz, Austria.
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Daniela Pinter
From the Department of Neurology (M.K., C.L., A.P., D.P., T.G., S.R., S.F., C.E., F.F.), Department of Radiology (Division of Neuroradiology) (C.E.), and Institute for Medical Informatics, Statistics and Documentation (G.B.), Medical University of Graz, Austria.
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Thomas Gattringer
From the Department of Neurology (M.K., C.L., A.P., D.P., T.G., S.R., S.F., C.E., F.F.), Department of Radiology (Division of Neuroradiology) (C.E.), and Institute for Medical Informatics, Statistics and Documentation (G.B.), Medical University of Graz, Austria.
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Gerhard Bachmaier
From the Department of Neurology (M.K., C.L., A.P., D.P., T.G., S.R., S.F., C.E., F.F.), Department of Radiology (Division of Neuroradiology) (C.E.), and Institute for Medical Informatics, Statistics and Documentation (G.B.), Medical University of Graz, Austria.
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Stefan Ropele
From the Department of Neurology (M.K., C.L., A.P., D.P., T.G., S.R., S.F., C.E., F.F.), Department of Radiology (Division of Neuroradiology) (C.E.), and Institute for Medical Informatics, Statistics and Documentation (G.B.), Medical University of Graz, Austria.
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Siegrid Fuchs
From the Department of Neurology (M.K., C.L., A.P., D.P., T.G., S.R., S.F., C.E., F.F.), Department of Radiology (Division of Neuroradiology) (C.E.), and Institute for Medical Informatics, Statistics and Documentation (G.B.), Medical University of Graz, Austria.
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Christian Enzinger
From the Department of Neurology (M.K., C.L., A.P., D.P., T.G., S.R., S.F., C.E., F.F.), Department of Radiology (Division of Neuroradiology) (C.E.), and Institute for Medical Informatics, Statistics and Documentation (G.B.), Medical University of Graz, Austria.
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Franz Fazekas
From the Department of Neurology (M.K., C.L., A.P., D.P., T.G., S.R., S.F., C.E., F.F.), Department of Radiology (Division of Neuroradiology) (C.E.), and Institute for Medical Informatics, Statistics and Documentation (G.B.), Medical University of Graz, Austria.
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Citation
Dynamics of brain iron levels in multiple sclerosis
A longitudinal 3T MRI study
Michael Khalil, Christian Langkammer, Alexander Pichler, Daniela Pinter, Thomas Gattringer, Gerhard Bachmaier, Stefan Ropele, Siegrid Fuchs, Christian Enzinger, Franz Fazekas
Neurology Jun 2015, 84 (24) 2396-2402; DOI: 10.1212/WNL.0000000000001679

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Abstract

Objective: We investigated longitudinal changes in iron concentration in the subcortical gray matter (caudate nucleus, globus pallidus, putamen, thalamus) of patients with clinically isolated syndrome (CIS) and definite multiple sclerosis (MS) and their relation to clinical and other morphologic variables.

Methods: We followed 144 patients (76 CIS; median Expanded Disability Status Scale [EDSS] 1.0 [interquartile range (IQR) 0.0–2.0]; 68 MS; median EDSS 2.0 [IQR 1.0–3.3]) clinically and with 3T MRI over a median period of 2.9 (IQR 1.3–4.0) years. Iron concentration was determined by R2* relaxometry at baseline and last follow-up.

Results: At baseline, subcortical gray matter iron deposition was higher in MS compared to CIS. In CIS, R2* rates increased in the globus pallidus (p < 0.001), putamen (p < 0.001), and caudate nucleus (p < 0.001), whereas R2* rates in the thalamus decreased (p < 0.05). In MS, R2* rates increased in the putamen (p < 0.05), remained stable in the globus pallidus and caudate nucleus, and decreased in the thalamus (p < 0.01). Changes in R2* relaxation rates were unrelated to changes in the volume of respective structures, of T2 lesion load, and of disability.

Conclusions: Iron accumulation in the basal ganglia is more pronounced in the early than later phases of the disease and occurs independent from other morphologic brain changes. Short-term changes in iron concentration are not associated with disease activity or changes in disability.

GLOSSARY

CIS=
clinically isolated syndrome;
EDSS=
Expanded Disability Status Scale;
FA=
flip angle;
FLAIR=
fluid-attenuated inversion recovery sequence;
FLASH=
fast low angle shot;
MPRAGE=
magnetization-prepared rapid gradient echo;
MS=
multiple sclerosis;
PBVC=
percentage of brain volume change;
RRMS=
relapsing-remitting multiple sclerosis;
TE=
echo time;
TI=
inversion time;
TR=
repetition time

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 2388

  • Received July 27, 2014.
  • Accepted in final form December 29, 2014.
  • © 2015 American Academy of Neurology
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