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    You are here : Home » MS Research News » Brain Iron Deposits

    Brain Iron Deposits

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    Increased iron accumulation occurs in the earliest stages of demyelinating disease

    Iron deposits in the brainAn ultra-high field susceptibility mapping study in Clinically Isolated Syndrome


    Objective: To determine, using ultra-high field magnetic resonance imaging (MRI), whether changes in iron content occur in the earliest phases of demyelinating disease, by quantifying the magnetic susceptibility of deep grey matter structures in patients with Clinically Isolated Syndrome (CIS) that is suggestive of multiple sclerosis (MS), as compared with age-matched healthy subjects.

    Methods: We compared 19 CIS patients to 20 age-matched, healthy controls. Scanning of the study subjects was performed on a 7T Philips Achieva system, using a 3-dimensional, T2*-weighted gradient echo acquisition. Phase data were first high-pass filtered, using a dipole fitting method, and then inverted to produce magnetic susceptibility maps. Region of interest (ROI) analysis was used to estimate magnetic susceptibility values for deep grey matter structures (caudate nucleus, putamen, globus pallidus, the thalamus and its pulvinar).

    Results: Significantly increased relative susceptibilities were found in the CIS group, compared with controls, for the caudate nucleus (p = < 0.01), putamen (p < 0.01), globus pallidus (p < 0.01) and pulvinar (p < 0.05). We found no significant nor consistent trends in the relationship between susceptibility and age for either the study controls or CIS patients, in any ROI (r2 < 0.5; p > 0.05). In CIS patients, the time elapsed since the clinical event and the Expanded Disability Status Scale (EDSS) scores were not correlated with iron levels in any ROI (r2 < 0.5; p > 0.05); however, a moderate correlation (r2 = 0.3; p < 0.01) was found between the T1 lesion load and the mean susceptibility of the caudate nucleus.

    Conclusion: CIS patients showed an increased iron accumulation, as measured using susceptibility mapping of the deep grey matter, suggesting that iron changes did occur at the earlier stages of CIS disease.

    Ali M Al-Radaideh1, Samuel J Wharton, Su-Yin Lim, Christopher R Tench, Paul S Morgan, Richard W Bowtell, Cris S Constantinescu, Penny A Gowland

    Source: Multiple Sclerosis Journal © 2012 by SAGE Publications (09/11/12)

    Using powerful MRI to track iron levels in brain could be new way to monitor progression of MS

    MRIMedical researchers at the University of Alberta have discovered a new way to track the progression of multiple sclerosis (MS) in those living with the disease, by using a powerful, triple strength MRI to track increasing levels of iron found in brain tissue.

    The researchers discovered that iron levels in MS patients are increasing in grey matter areas of the brain that are responsible for relaying messages. High iron levels in a specific "relay area" were noted in patients who had physical disabilities associated with MS.

    Iron is very important for normal function of the brain and the amount of iron is a tightly controlled system by the brain tissue. The discovery suggests there is a problem with the control system. Too much iron can be toxic to brain cells and high levels of iron in the brain have been associated with various neurodegenerative diseases. But to date, no tests have been able to quantify or measure iron in living brain.

    Alan Wilman and Gregg Blevins, co-principal investigators from the Faculty of Medicine & Dentistry, used a new MRI method to quantitatively measure iron in the brain to gain a better understanding of what the disease is doing in the brains of those who were recently diagnosed with MS. Twenty-two people with MS took part in the study, along with 22 people who did not have the condition.

    "In MS, there is a real desire and need to get a good idea of the state and progression of the disease," says Blevins, who is both a practising neurologist and a researcher from the Division of Neurology.

    "When patients with MS currently get an MRI, the typical measures we look at may not give us a good idea of the nature and state of MS. Using this new MRI method would give physicians a new way to measure the effectiveness of new treatments for patients with MS by watching the impact on iron levels. This opens up the idea of having a new biomarker, a new way of looking at the disease over time, watching the disease, seeing the progression or lack of progression of the disease, a new way to track it."

    Wilman, a researcher and physicist in the Department of Biomedical Engineering, says the new MRI method may be a better gauge for disease progression than strictly looking at number and frequency of relapses.

    "This is a new quantitative marker that gives us more insight into MS. We can get a better handle on where patients are at. In terms of clinical symptoms, they may be fine for quite awhile, then they have a relapse, then they're fine for quite awhile. Well, the time when they are actually fine, they may not actually be alright.

    "The disease may be progressing, but there is just no marker right now that shows that. We think the biomarker we have discovered could be an answer. People in the medical research community are very excited about this discovery, because it could be a new way of looking at the disease."

    The new MRI method, which uses a machine that is 90,000 times the strength of the earth's magnetic field, will give physicians more detail and information about the impact of MS on the brain, insight that doctors and researchers didn't have before.

    "This could be a very early marker of MS. We'd like to see this new method used with all patients who have MS. Ultimately, this discovery is a great example of translational research."

    The researchers hope to see this new MRI method used in clinical trials for patients with MS within the next one to two years, then to be regularly used by physicians within five years.

    Blevins and Wilman both credit the MS patients who took part in the study. "If patients weren't so willing to help, we couldn't do any of this," said Wilman.

    *This discovery is not a confirmation of CCSVI because this discovery looks at iron existing in brain tissue, not iron from the blood.

    The research study was funded by the Canadian Institutes of Health Research, the Natural Sciences and the Engineering Research Council of Canada, the Multiple Sclerosis Society of Canada and the University of Alberta Hospital Foundation.

    Source: Eureka Alert! (16/12/11)

    Brain iron serves as marker for MS

    Brain Iron DepositsIron accumulation in the basal ganglia was found in patients with advanced multiple sclerosis (MS), but not in patients with a clinically isolated syndrome (CIS) that is suggestive of MS, Austrian researchers reported.

    In this quantitative study, 113 MS and CIS patients, as well as 35 healthy controls, underwent 3T MRI imaging, which showed increased levels of brain iron in MS patients compared with CIS patients (P<0.001) and healthy controls (P<0.005), wrote Franz Fazekas, MD, of the Medical University of Graz, and colleagues in Neurology.

    MRI-based iron mapping has been proposed as a marker of neurodegeneration in various neurologic disorders, including MS, explained Alex Rovira, MD, from the Hospital Vall d'Hebron in Barcelona, in an accompanying editorial. "Iron is an essential trace element with a vital role in normal brain metabolism, oxygen transport, myelin production, and neurotransmitter synthesis, and in reactions critical to oxidative stress," he wrote.

    Abnormal iron accumulation has been identified pathologically in MS, but few studies have investigated brain iron levels in patients with CIS, the investigators stated. Recently R2* relaxometry has been validated for measuring brain iron.

    Of the 113 consecutive patients, 78 had MS and 35 had CIS. Along with the MR studies, the participants underwent clinical and neuropsychological examination. Iron deposition in subcortical gray matter was assessed by automated, regional calculation of R2* rates.

    In addition to significantly increased R2* levels in the basal ganglia of MS patients, the authors found that the levels correlated with age (r=0.5, P<0.001), disease duration (r=0.5, P<0.001), the Expanded Disability Status Scale (r=0.3, P<0.005), and the z values of mental processing speed (r=-0.3, P< 0.01).

    The regional brain R2* relaxation rates were as follows in CIS, MS, and controls, respectively:

    Basal ganglia: 25 (CI 23.7 to 26.7) versus 27.9 (CI 25.8 to 29.4) versus 25.6 (CI 24.6 to 28.5)
    Putamen: 22.6 (CI 21.8 to 24) versus 25.3 (CI 23.3 to 27.8) versus 23.7 (CI 22.2 to 26.1)
    Pallidum: 31.7 (CI 29.8 to 33.8) versus 35.3 (CI 33.3 to 27.4) versus 33 (CI 20.9 to 35.2)
    Caudate: 20.1 (CI 19.1 to 21.4) versus 22.4 (CI 10.7 to 24) versus 21.1 (CI 20 to 22.9)

    The difference between basal ganglia R2* relaxation rates in MS and CIS was statistically significant (P<0.001) as was the difference between MS and healthy controls (P<0.005), the authors stated. Also, the difference between CIS and controls was significant at P<0.05.

    Stepwise linear regression analysis revealed gray matter atrophy as the strongest independent predictor of basal ganglia R2* levels (P<0.001), followed by age (P< 0.001), and T2-lesion load (P<0.005).

    Basal ganglia iron accumulation in MS occurs with advancing disease and is related to the extent of morphologic brain damage, the researchers said. These study results argue for iron deposition as an epiphenomenon, and the absence of increased iron levels in patients with CIS indicates that iron accumulation does not precede the development of MS, they explained.

    Once iron accumulates within the brain, subsequent oxidative stress-induced tissue damage may enhance the extent of axonal damage and of neurodegeneration, Fazekas said. However, given the limitations of this study, he added that the present findings do not support a strong role of such a mechanism. It would be important to examine more advanced stages of MS and to obtain longitudinal data, he concluded.

    Rovira, along with co-editorialist Xavier Montalban, MD, PhD, said this study should be looked at as a "first step ... the second step will require reproducing these preliminary results in an MS cohort with a wide range of physical disability." The study only included patients with mild physical disability, which is not representative of the full spectrum of the disease, he added.

    Subsequent studies will have to determine whether the MR technique is sensitive to iron content changes in deep gray matter structures, visible MS lesions, and in normal-appearing brain tissue, "as this would provide better assessment of the diffuse pattern characterizing MS," Rovira said.

    Fazekas serves on scientific advisory boards for a variety of drug companies including Bayer, Schering Pharma, Biogen, Merck Serono, Novartis, D-pharma, and Teva Pharmaceutical Industries. Other authors reported research support from the Austrian Fund and various drug companies.

    Rovira serves on scientific advisory boards for NeuroTEC, Bayer Schering Pharma, and BTG International. He has received speaker honoraria from Bayer Schering Pharma, sanofi-aventis, Bracco, Merck Serono, Teva Pharmaceutical Industries, and Biogen Idec. He receives research support from Bayer Schering Pharma.

    Montalban has received research support for clinical trials from Genentech, Genzyme, and Wyeth. He receives research support from the Fundacio Esclerosi Multiple (FEM, Multiple Sclerosis Foundation).

    Primary source: Neurology
    Source reference:
    Kahil M, et al "Determinants of brain iron in multiple sclerosis: A quantitative 3T MRI study" Neurology 2011; 77: 1691–1697.

    Additional source: Neurology
    Source reference:
    Rovira A, et al "MR brain iron mapping in MS -- A potential neurodegenerative marker or just another technique?" Neurology 2011; 77: 1660–1661.

    Source: MedPage Today © 2011 Everyday Health, Inc. (03/11/11)

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