Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gray Matter Damage in the Brain of MS Patients Linked to Cognitive, Physical Deficits, New UB Research Finds

22.10.2003


Results further implicate iron deposits in brain in MS impairments



The mental impairment and problems with walking experienced by patients with multiple sclerosis (MS) are linked to damage in the brain’s gray matter, with MRI findings suggesting the damage is due to toxic deposits of iron, researchers from the University at Buffalo have shown for the first time.
Previous breakthrough work by the team had linked deep gray matter iron deposits to the disease course of MS, brain atrophy and overall disability, but not to cognition or ambulation. Results of these latest studies were presented today (Oct. 21, 2003) at the annual meeting of the American Neurological Association in San Francisco.

The researchers, affiliated with the Buffalo Neuroimaging Analysis Center (BNAC) and Jacobs Neurological Institute, use specialized, computer-assisted magnetic resonance imaging (MRI) technology to focus on hypointensity, or unnatural darkness, of gray matter structures as seen on so-called T2-weighted images. This condition is referred to as T2 hypointensity. Using this approach, they were able to show that structures in the brain’s deep gray matter of MS patients contained T2 hypointensity compared with normal individuals, suggesting higher-than-normal levels of iron deposits, and confirmed the relationship of T2 hypointensity to MS symptoms.



"Traditionally, we thought MS was strictly a ’white matter disease,’ involving the brain’s neural pathways that allow various gray-matter structures to communicate with each other," said Rohit Bakshi, M.D., UB associate professor of neurology, first author on the new studies and founding director of the BNAC. "Through our computerized imaging analysis capabilities, we were able to visualize gray matter structures deep in the brain of MS patients and found some to be atrophied.

"We also found MRI evidence of abnormally high levels of iron," he said. "Moreover, these changes weren’t associated with the amount of white-matter damage, so this was all new information. If we’re going to treat this disease, we have to know where the damage is."

The finding concerning gray matter atrophy resulted from the researchers’ work with a brain structure called the caudate nucleus, which is an important nerve center for controlling movement and cognitive processing. Other laboratories have studied the role of the caudate nucleus in Alzheimer’s disease and Huntington’s disease, but the BNAC is the only center studying it in MS patients using state-of-the-art MRI techniques.

The current studies take the BNAC’s previous research to the next level, in an effort to determine the role of excess iron in specific MS disabilities. Bakshi and colleagues tested walking ability and cognitive impairment respectively in two groups of MS patients that underwent the specialized MRI brain scans to assess T2 hypointensity of the gray matter structures thought to be involved in these conditions.

The ambulatory study involved 41 MS patients who completed a timed 25-foot walk, a standard measure of physical dysfunction. These times were compared with T2 hypointensity in the gray matter, as well as brain atrophy and additional anatomical brain changes known to occur in MS. Results showed that T2 hypointensity was the only brain change directly associated with impaired walking ability, and the strongest association with walking ability pointed to the brain structure known as the dentate nucleus. This structure exists deep in the cerebellum, the brain region responsible for coordination and smooth movement of the limbs.

The study of cognitive impairment involved 28 MS patients who took tests measuring learning, speed of information processing and working memory. Test results were compiled into an attention/memory composite, which was compared with the same measures of brain change used in the ambulation assessment. T2 hypointensity in the brain’s deep gray matter structures was the only measure that predicted cognitive impairment in these patients, results showed.

"We suspect that MS patients have defective blood-brain barriers, the cell layer that prevents potentially toxic substances from entering the brain," Bakshi said. "Excessive iron entering the brain may damage the deep gray matter structures through generation of free radicals and lipid peroxidation, as well as inflammation, all of which would destroy neurons. We have tissue samples from two autopsied brains showing high iron levels in these gray matter structures in patients with MS compared to controls."

Bakshi said the other possibility is that high levels of iron are a result of the neurodegenerative process that occurs in MS. "When brain cells are destroyed, in aging for example, iron levels increase in the brain. High levels of iron also are seen in Alzheimer’s and Parkinson-related diseases. There is still a debate about cause-effect of iron in all of these conditions.

"We do think, however, that hypointensity in the deep gray matter is a strong predictor of disability, progression of the disease and subsequent brain atrophy in MS," he said. "If future longitudinal studies support these findings, it may be possible to design a new treatment to prevent iron build-up, which could prove beneficial to MS patients. However, we must have further studies to draw definitive conclusions," stated Bakshi.

Additional researchers on the studies were Christopher Tjoa, a first-year UB medical student; Ralph Benedict, Ph.D., UB neuropsychologist and associate professor of neurology; Andrew Fabiano, third-year UB medical student; Jitendra Sharma, M.D., a graduate student at Roswell Park Cancer Institute; Robert Bermel, fourth-year UB medical student; Frederick E. Munschauer, M.D., professor and chair of the UB Department of Neurology, and Bianca Weinstock-Guttman, M.D., assistant professor of neurology.

The studies were funded by grants from the National Institutes of Health, National Science Foundation and the National Multiple Sclerosis Society, and by an Alpha Omega Alpha medical school research fellowship and an American Academy of Neurology Student Interest in Neurology Summer Scholarship.

Lois Baker | University at Buffalo
Further information:
http://www.buffalo.edu/news/fast-execute.cgi/article-page.html?article=64280009

More articles from Health and Medicine:

nachricht Chances to treat childhood dementia
24.07.2017 | Julius-Maximilians-Universität Würzburg

nachricht World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

Ultrathin device harvests electricity from human motion

24.07.2017 | Power and Electrical Engineering

Scientists announce the quest for high-index materials

24.07.2017 | Materials Sciences

ADIR Project: Lasers Recover Valuable Materials

24.07.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>