Determinants of iron accumulation in deep grey matter of multiple sclerosis patients.
BACKGROUND
Iron accumulation in deep grey matter (GM) structures is a consistent finding in multiple sclerosis (MS) patients. This study focused on the identification of independent determinants of iron accumulation using R2* mapping.


METHODS
Ninety-seven MS patients and 81 healthy controls were included in this multicentre study. R2* mapping was performed on 3T MRI systems. R2*in deep GM was corrected for age and was related to disease duration, disability, T2 lesion load and brain volume.


RESULTS
Compared to controls, R2* was increased in all deep GM regions of MS patients except the globus pallidus and the substantia nigra. R2* increase was most pronounced in the progressive stage of the disease and independently predicted by disease duration and disability. Reduced cortical volume was not associated with iron accumulation in the deep GM with the exception of the substantia nigra and the red nucleus. In lesions, R2* was inversely correlated with disease duration and higher total lesion load.


CONCLUSIONS
Iron accumulation in deep GM of MS patients is most strongly and independently associated with duration and severity of the disease. Additional associations between cortical GM atrophy and deep GM iron accumulation appear to exist in a region specific manner.
Medical University of Graz, Auenbruggerplatz 22, 8036 Graz, Austria stefan.ropele@medunigraz.at.
Stefan
S
Ropele
VU University Medical Center, The Netherlands.
Iris D
ID
Kilsdonk
VU University Medical Center, The Netherlands.
Mike P
MP
Wattjes
Medical University of Graz, Austria.
Christian
C
Langkammer
VU University Medical Center, The Netherlands.
Wolter L
WL
de Graaf
Copenhagen University Hospital, Denmark.
Jette L
JL
Frederiksen
Copenhagen University Hospital, Denmark.
Henrik B
HB
Larsson
UCL Institute of Neurology, UK.
Marios
M
Yiannakas
UCL Institute of Neurology, UK.
Claudia Am
CA
Wheeler-Kingshott
Medical University of Graz, Austria.
Christian
C
Enzinger
Medical University of Graz, Austria.
Michael
M
Khalil
Institute of Experimental Neurology, Vita-Salute San Raffaele University, Italy.
Maria A
MA
Rocca
University Hospital Basel, Switzerland.
Till
T
Sprenger
University Hospital Basel, Switzerland.
Michael
M
Amann
University Hospital Basel, Switzerland.
Ludwig
L
Kappos
Institute of Experimental Neurology, Vita-Salute San Raffaele University, Italy.
Massimo
M
Filippi
Vall d'Hebron University Hospital, Spain.
Alex
A
Rovira
UCL Institute of Neurology, UK/NIHR UCL-UCLH Biomedical Research Centre, UK.
Olga
O
Ciccarelli
VU University Medical Center, The Netherlands.
Frederik
F
Barkhof
Medical University of Graz, Austria.
Franz
F
Fazekas
D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D066128:Gray Matter / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007501:Iron / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
D007501:Iron
Expanded Disability Status Scale; Multiple sclerosis; R2*; age; brain; brain volume; deep grey matter; disease duration; iron